Biomedical Applications of Interpenetrating Polymer Network System

Mohd Fuzail Qadri*, Rishabha Malviya , Pramod Kumar Sharma
Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Gautam Buddha Nagar, Uttar Pradesh, India

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* Address correspondence to this author at the Department of Pharmacy, School of Medical and Allied Sciences,Galgotias University, Plot No. 2, Sector 17-A, Yamuna Expressway,Greater Noida, Gautam Buddha Nagar, Uttar Pradesh, India; Tel: +91 9716037762; E-mail:


Interpenetrating polymer network (IPN) has been regarded as one of the novel technology in recent years showing the superior performances over the conventional techniques. This system is designed for the delivery of drugs at a predetermined rate and thus helps in controlled drug delivery. Due to its enhanced biological and physical characteristics like biodegradability, biocompatibility, solubility, specificity and stability, IPN has emerged out to be one of the excellent technologies in pharmaceutical industries. This article focuses mainly on the biomedical applications of IPN along with its future applicability in pharmaceutical research. It summarizes various aspects of IPN, biomedical applications and also in-cludes the different dosage forms based on IPN.

Keywords: Biomedical, double network, drug delivery, IPN, tissue engineering.


The concept of IPN goes back as far as 1914 and the first interpenetrating polymer network (IPN) was invented by Aylsworth and the term IPN was firstly given by Miller in 1960s in a scientific study about polystyrene network [1]. An Interpenetrating polymer network may be defined as any material which contains two or more polymers in the network form [2]. IPN is obtained when at least one of the polymers is synthesized or cross-linked in the immediate presence of the other polymer without any covalent bond between them [3].

In other words, IPN may also be defined as the combination of two or more polymers in the network form in which one polymer is cross-linked in the presence of other [4]. There are three conditions of polymer which are necessary in the composition of IPN. These conditions are as follows [5]:-

1) At least two polymers must be synthesized and cross-linked in the presence of the other.

2) Both polymers have similar kinetics.

3) Polymers are not dramatically phase separated.

An IPN is differentiating from other polymer combination in two ways [6]:-

1) IPN swells, but does not dissolve in the solvent.

2) Prevents the action of creep and flow.

They are also different from polymer complex and graft co-polymer because they either involve in chemical bond or in low degree of cross-linking. From this point of view only, IPN can be generally named as “polymer alloys” [7]. IPN is not prepared by normally mixing the two or more polymers and also does not produce from co-polymers. IPN based drug delivery system may follow zero order pattern with less fluctuation [8]. IPN is regarded as novel biomaterial. A combination of polymers, i.e. synthetic and natural polymers, is useful in increasing the release of short half-lived drug under physiological condition [9]. If we increase the mechanical properties of IPN, it will be acceptable for preparing microsphere for controlled drug delivery [10]. The chemical and physical combination method as well as properties of multi-polymers play as important role in the controlled release of the drug because they help to provide a convenient route for the modification of properties to meet specific needs. Among these methods, IPN based drug delivery system is one of the newly developed method for designing the novel controlled release drug delivery system [11].

Double network gels also obtained from interpenetrating polymer network where the properties of two networks can be done in contrast such as, rigidity, molecular weight, network density etc. They are generally synthesized with the help of two steps:- in first step, they are synthesized by sequential free-radical polymerization process. In this process, the highly relative molecular mass is neutral. In the second step, polymer network is incorporated with in a swollen heterogeneous polyelectrolyte 1st network [12].

IPN formulation is one of the important/successful methods for developing a product with better physico-mechanical properties than the normal polyblends [13]. IPN can be made in different ways. IPN is also found in the form of latex which is known as interpenetrating electrometric network (IEN) [14]. Gradient IPN is one of the other forms which is formed when the film made with a network of one polymer on the one surface and the network of another polymer on the other surface, there is a gradient inside the film. On the other hand, when one polymer is cross linked and another is linear or branched, it is called semi-IPN [15].

IPNs can be prepared through different techniques as given in the literature but in-situ technique proves that it is the most convenient technique. In this technique, all reactants are combined together and reaction can take place with the formation of two networks which can be started at the same time [16]. The procedure for the synthesis of IPNs can be divided in to two categories-

1. Simultaneous synthetic method: In simultaneous synthetic method, both monomers are mixed together to form polymer network simultaneously through different reaction routes.

2. Sequential synthetic method: In sequential synthetic method, different network reactions are controlled sequentially by adding different monomers. Now a days, mostly commercial materials are prepared by sequential IPNs, because of their flexibility and easy to process ability.

When IPNs are used for coating purpose, they cannot be prepared by the sequential or simultaneous interpenetrating polymerization because of the presence of volatile monomer. For this purpose, they can be prepared from preforming pre-polymers which contain complementary functional groups that increase their miscibility [17]. In IPNs, cross linking of mutual chain entanglement produce finer dispersion of one polymer in to the other [18].

Advantages of IPN [19, 20]: There are the following inherent advantages due to which IPN system gained huge popularity in the modern era of polymers. They are as follows-

1. IPN system helps in increasing the mechanical strength, phase stability and biological acceptability of the final product.

2. IPN is also helpful in producing the synergistic effect from the component polymer.

3. Due to the infinite zero-viscosity of the gel, phase separation between the component polymers is not possible.

4. Due to permanent interlocking of the network segment, thermodynamic incompatibility can be made to overcome as the reacting ingredients are blended thoroughly at the time of synthesis.

5. IPN also potent to develop the controlled release system for delivering the drug.

6. When the blends are subjected to stress they keep the phases separate.

Disadvantages of IPN [21, 22]: The main disadvantage of IPN is that, sometimes the polymers interpenetrate to such an extent and the drug released from the matrix becomes difficult. The problem with the non-covalent system is that it can also be a problem with the covalent system due to the lack of an effective interface.

Features of IPN [2, 23]: There are the following ideal characteristics of IPN which are as follows-

1. In ideal IPN creep and flow is suppressed.

2. IPN can swell but does not dissolve in solvent.

3. IPN has high tensile strength.

4. Most ideal IPNs are heterogeneous systems which contain one rubbery phase and one glassy phase to produce a synergistic effect yielding.

5. When the blends are subjected to stress, they keep the phases separated together.

6. IPN mainly forms insoluble network.

7. IPN systems differ mainly due to the number and types of cross-links.

8. They show adhesive property.

9. Hence, IPN based systems have gained good potential to develop the controlled release delivery of drugs.

IPN based Drug Delivery System: IPN based drug delivery systems are used to deliver the drug at a specific rate for desired period of time with low fluctuation.

Now a days, there are many approaches which are being used for improving the delivery of therapeutic materials like- films, hydrogels, tablets, capsules, microspheres, sheets, sponges, matrix, transdermal patches, nanoparticles etc. some of the important IPN based drug delivery systems are discussed here [24].

Films: IPN based films are used as piezodialysis membrane which are non-mosaic membrane. The important application of IPN delivery system is the uralkyd/poly (glycidylmethacrylate) based film which shows better mechanical and tensile strength [3, 25]. Biodegradable collagen films or matrices have served as scaffolds for the survival of transfected fibroblasts [26].

IPN based films which are prepared by the mixture of collagen and polyvinyl alcohol, cross-linked with glutaraldehyde vapor shows depot formulation for recombinant human growth hormones [27]. In many animal models, after implantation of transfected cells, a long term expression of the foreign gene has not been achieved [28]. Suh et al., studied the graft copolymerization of type I atelocollagen onto the surface of polyurethane (PU) films treated with ozone was performed [29]. It has been observed that they could enhance an attachment and proliferation of fibroblasts and growth of cells.

An interesting use of thermo-responsive polymer films was shown by Zakharchenko et al., prepared a belayed of PVCL on top of PNIPAAm with encapsulated magnetic nanoparticles [30]. At temperatures greater than the lower critical solution temperature (LCST) the films were flat and allowed for adsorption of nanoparticles, cells or drugs onto the surface, upon cooling the films rolled up entrapping the absorbed particles which could then be released by heating again. This is a novel approach for the encapsulation and release of nanoparticles and cells with the addition of the magnetic particles allowing manipulation of the films by an external field [31]. Some of the IPN based films with their applications are shown in Table 1.

Table 1.

List of the drugs delivered through IPN based films.

S.No. Name of Polymers Cross-linker Drug Formulation Reference
1. Polyurathane+ Polysiloxane Phenol formaldehyde Resin _ Polymer Film [3]
2. Chitosan + Xanthan Gum Glutaraldehyde Amoxicillin Hydrogel Film [32]
3. Sod. Alginate + Gelatin Calcium Azure B IPN Film [33]
4. Polyvinyl Alcohol + Polyacrylic Acid Glutaraldehyde Crystal violet IPN film [34]
5. Polydimethylacrylamide + hyaluronic acid + glucose oxidase - - Semi-IPN Film [35]
6. Prevulcanized Natural Rubber latex + Chitosan Glutaraldehyde - Semi-IPN Film [36]
7. Methoxyoligo(oxyethylene)methacrylate + Poly(methylmethacrylate) 1,4 butane-diol-dimethyl amide - IPN Film [3]
8. Chitosan + hypromellose + citric acid Genipin Curcumin Semi-IPN Film [37]
9. Polyaniline + Polyvinyl alcohol Ammonium persulfate - Thin Film [38]
10. Polyurethane urea, N -isopropylacrylamide, acrylic acid, and Butylmethacrylate - - Semi-IPN Film [39]
11. Aluminum substrate + 1,4-butylene glycol Trimethylolpropane - IPN Thin Film [40]
12. Hemicellulose+ Chitosan Glutaraldehyde - Semi-IPN Hydrogel Film [41]
13. 2-hydroxy-3-methyacryl-oxypropyl trimethylammonium chloride (HMPTAC) + ethylene glycol dimethacrylate (EGDMA) - - IPN Film [42]
14. Poly(dimethylsiloxane) + Polyethylene glycol + Chitosan Hexamethylene-1,6-di-(aminocarboxysulfonate) - Bioadhesive Film [43]
15. Chitosan +  Poly(aniline) Glutaraldehyde - Biosensor Film [44]
Table 2.

List of the drugs delivered through IPN based hydrogel.

S.No. Name of Polymers Cross-linker Drug Formulation Reference
1. Chitosan + Polyvinyl pyrrolidone Glutaraldehyde Clarithromycin Semi-IPN Hydrogel [53]
2. Polydimethylsiloxane / polyethylene glycol + chitosan Hexamethylene-1,6-di-amino carboxysulfone - Semi-IPN Hydrogel [43]
3. Gelatin + Methacrylic acid Glutaraldehyde and Methylene bisacrylamide Glipizide IPN Hydrogel [54]
4. Chitosan + Polyvinyl pyrrolidone + Polyacrylic acid Glutaraldehyde and N,N-methylene bisacrylamide Clarithromycin IPN Hydrogel [55]
5. Methacrylic acid + Polyethylene glycol Tetra
Atorvastatin, Theophyllin Hydrogel [3]
6. Locust bean gum (Carboxymethyl sulfate derivative) - Tramadol HCl Hydrogel Beads [56]
7. Chitosan + Polyanilin Glutaraldehyde - Semi-IPN Hydrogel [44]
8. Chitosan and Polyacrylamide - - Semi-IPN Hydrogel [57]
9. Sodium Alginate + Poly(lactic acid) Glutaraldehyde Penicillamine IPN Hydrogel [58]
10. Poly(Ethylene Oxide) + Poly(Methyl Methacrylate) - - IPN hydrogels [59]
11. Konjac glucomannan + Polyacrylic acid N,N-methylene-bis-acrylamide - IPN Hydrogels [60]
12. Chitosan + Polyvinyl alcohol Glyoxal - IPN Hydrogels [61]
13. Gelatin + Polyvinyl alcohol Transglutaminase enzyme - IPN Hydrogels [52]
14. Polyacrylamide-co-solfopropylacrylate potassium + Polyacrylonitrile N,N-methylene-bis-acrylamide - IPN Hydrogel [62]
15. Polybutyl acrylate + Polyhydroxylethyl acrylate Ethylene glycol dimethacrylate Iron Oxide Hydrogel [3]
Table 3.

List of the drugs delivered through IPN based microspheres.

S.No. Name of Polymers Cross-linker Drug Formulation References
1. Sodium alginate + Polyvinyl alcohol Glutaraldehyde Diclofenec Sodium IPN Microspheres [70]
2. Gellan gum + Poly(N-isopropylacrylamide) - Atenolol Semi-IPN Microspheres [71]
3. Sodium alginate + Poly (vinyl alcohol) Glutaraldehyde Naproxen IPN Microspheres [72]
4. Xanthan gum + Superabsorbent polymers + Poly(vinyl alcohol) N,N’-methylene bisacrylamide Ciprofloxacin HCl IPN hydrogel microspheres [65]
5. Chitosan + Hydroxyethyl cellulose Glutaraldehyde Isoniazid IPN blends microspheres [73]
6. Hydroxypropyl -methylcellulose + Poly
(vinyl alcohol)
Glutaraldehyde Ciprofloxacin
IPN Microspheres [74]
7. Acryl amide grafted Carboxymethylcellulose + Sodium alginate Glutaraldehyde Triprolidine hydrochloride Monohydrate IPN Microspheres [75]
8. Sodium carboxymethyl cellulose + poly(vinyl alcohol) Glutaraldehyde Diclofenac Sodium IPN Hydrogel Microspheres [76]
9. Chitosan + Methylcellulose Glutaraldehyde Theophylline IPN Microspheres [11]
10. Chitosan + Gelatin Glutaraldehyde Isoniazid IPN Microspheres [77]
11. Gelatin + Sodium carboxymethyl
Glutaraldehyde Ketorolac
Semi-IPN Microspheres [78]
12. Acrylamide grafted dextran + Chitosan - Acyclovir Semi-IPN Microspheres [4]
13. Lepidium sativum + poly(vinyl alcohol) Glutaraldehyde Simvastatin IPN Microspheres [10]
14. Chitosan + guargum-g-acrylamide Glutaraldehyde 5-Fluorouracil Semi-IPN Microspheres [79]
15. Locust bean gum + Poly vinyl alcohol Glutaraldehyde Metformin HCl IPN Mucoadhesive
Table 4.

List of the drugs delivered through IPN based tablets.

S.No. Name of Polymers Cross-linker Drug Formulation References
1. Polyacrylamide grafted-sodium alginate + Sodium alginate Ca2+ ion Diltiazem HCl IPN Matrix
2. Sodium alginate + Carrageenan - Propranolol HCl IPN matrix tablets [82]
3. Tamarind Seed Polysaccharide + Sodium Alginate - Propranolol HCl IPN hydrogel tablets [84]
Table 5.

List of the drugs delivered through IPN based sponges.

S.No. Polymers Cross-linkers Drug Formulation References
1. Chitosan + Poloxamer - - Semi-IPN Sponges [25]
2. Elastin + Collagan Glutaraldehyde - IPN Sponges [89]
3. Collagen + Fibronectin Glutaraldehyde Hyaluronic acid IPN Sponges [90]
4. Elastin + Collagen Glutaraldehyde Glycosaminogycans IPN Sponges [91]
5. Collagen + fibroblast - - IPN Sponges [92]
Table 6.

List of the drugs delivered through IPN based capsules.

S.No. Name of Polymers Cross-linker Drug Formulation Reference
1. Polyacrylamide + polyvinyl alcohol - Crystal violet and Bromothymol blue IPN Capsules [94]
Table 7.

List of biomedical applications.

S.No. Polymers Drug Applications References
1. Xanthan gum + Poly vinyl alcohol Ciprofloxacin hydrochloride Sustained release application. [65]
2. Polypropylene + Collagen gel - Abdominal wall repair in dogs [95]
3. Gum ghatti + poly vinyl alcohol Ranitidine HCl Mucoadhesive microspheres for anti-ulcer drug delivery [96]
4. Polyacrylamide-co-ethylene glycol +acrylic acid - Modulate bone formation in the peri-implant region in the rat femoral ablation model. [97]
5. Chitosan + Poly(acrylic acid-co-acrylamide) Insulin Superporous hydrogel for oral delivery [98]
6. Alginate + Chitosan - Improved cartilage tissue engineering [99]
7. Honeycomb + Collagen - Dermal tissue engineering [100]
8. Gelatin + Chitosan Propranol HCl Microsphere for nasal delivery. [101]
9. Poly(2-acrylamide-2-metyl-propane sulfonic acid) + Poly(N,N0-dimetylacrylamide) - Artificial cartilage [12]
10. Chitosan + Alanine Chlorpheniramine Oral controlled release of drug [102]
11. Collagen + hydrated gel - Development of bioengineered
tissues such as heart valves, blood vessels and
12. Collagen + Chitosan - Cartilage Scaffolds: Test anticancerous drugs and in-vitro culture of human epidermoid carcinoma
cells (HEp-2)
13. Locust Bean Gum + Poly (vinyl alcohol) Metformin HCl Mucoadhesive Microspheres for
Controlled Release
14. Chitosan + Poly(aniline) - Biosensor film [44]
15. Chitosan + Guargum-g-acrylamide. 5-Fluorouracil Microspheres for controlled release and improve the bioavailability of drug [79]
16. Chitosan + Poloxamer Sponge for wound dressing [105]
17. Chitosan + Poly(vinyl pyrrolidone) Clarithromycin H.pylori infection and management of  peptic ulcer [55]
18. Chitosan + Poly(dimethylsiloxane) + Polyethylene glycol - Bioadhesive Film [43]
19. Hydroxyl ethyl cellulose + Chitosan Isoniazide Blend microspheres for oral controlled release [77]
20. Hydroxyapatite + Collagen + bone morphogenetic protein - Acquired
and Congenital Orthopaedic defects
21. Polyvinyl pyrrolidone + Chitosan Amoxicilline Controlled release system for antibiotics [107]
22. Collagen + Hydroxyapatite - Bone Tissue engineering [108]
23. Polyacrylamide + Poly(ethylene
- Controlled inflammatory response [109]
24. Chitosan + Acryl amide-g-poly (vinyl alcohol) Cefadroxil Micro gel for oral controlled release of drug [110]
25. Acrylic acid + Chitosan - Corneal epithelial wound healing [111]
26. Chitosan + Poly vinyl alcohol Clarithromycin Controlled released hydrogel microsphere [112]
27. Dextran-g-acryl amide + Chitosn Theophylline IPN Microsphers for Oral controlled release [69]
28. Chitosan + Hydroxypropyl cellulose Valganociclovir hydrochloride Controlled Release of an Anti HIV Drug [113]

Hydrogel: To determine potential in a drug delivery system, hydrogel formulations were prepared by the combination of polymers [45]. Hydrogels are the three dimensional polymeric network which are chemically cross-linked [46] and have the capacity to hold the water in its structure due to the presence of hydrophilic functional groups [47].

Development of Smart Drug Delivery System (SDDS) which is also known as Stimuli-sensitive delivery system is one of the major success in drug delivery by IPN Hydrogels. The concept of SDDS is based on the conversion of physic-chemical properties of the polymer system [48]. Hydrogels are widely used in drug carrier because of its self-application and due to its easily manufacturing. IPN Hydrogels were prepared to increase the mechanical strength of the natural polymers. Hydrogels was also found resilient and stable [49]. Environmentally sensitive hydrogels can be produced from hydrophilic, stimuli-responsive polymer networks that can change the volume in response to an external signal such as a change in temperature or chemical environment. These materials are attractive and candidate for various biomedical applications and artificial muscles [50]. In situ forming IPN hydrogels of calcium alginate and dextran hydroxyethyl-methacrylate were developed and evaluated for protein release as well as for the behavior of embedded cells. It was observed that after an initial burst release bovine serum albumin was gradually released from the IPN hydrogels for up to 15 days. Encapsulation of expanded chondrocytes in the IPNs revealed that cells remained viable and were able to re-differentiate. IPN was described as a promising system as injectable in situ forming hydrogels for protein delivery and tissue engineering applications [51].

Eltjani-Eltahir Hago et al. developed interpenetrating polymer network PVA/GE hydrogels by a combination of enzymatic and physical methods, used freezing-thawing process and in situ with synthesis of gelatin/mTG in PVA solution. The morphology and crystalline structures of interpenetrating polymer network PVA/GE were also observed by some experimental analysis techniques, such as scanning electronic microscope (SEM). Moreover, in order to understand the initial behavior of fibroblasts cells, proliferation was assessed in vitro using fibroblast like L 929 cell culture [52].

Steffensen et al., developed soft hydrogels interpenetrating silicone, a polymer network for drug-releasing medical devices. IPN materials with PHEMA content in the range of 13%–38% (w/w) were synthesized by using carbon dioxide-based solvent mixtures under high pressure. These IPNs were characterized with regard to microstructure as well as ability of the hydrogel to form a surface-connected hydrophilic carrier network inside the silicone. A critical limit for hydrogel connectivity was found both via simulation and by visualization of water uptake in approximately 25% (w/w) PHEMA, indicating that entrapment of gel occurs at low gel concentrations. The optimized IPN material was loaded with the antibiotic ciprofloxacin, and the resulting drug release was shown to inhibit bacterial growth when placed on agar, thus demonstrating the potential of this IPN material for future applications in drug-releasing medical devices [114]. Some of the IPN based hydrogels with their applications are shown in Table 2.

Microspheres: Microspheres are one of the classes of newest IPN based drug delivery system. Microspheres are free flowing powder, which are solid usually small spherical particles made up of natural or synthetic polymers and ideally having a particles size range from 1-1000 µm in diameter [63]. Microspheres are the carrier linked delivery system having a core which contains drug and outer layer of polymer as coating material [64]. IPN microspheres are the versatile carrier for controlled release of the drug and also for the targeting application because they encapsulate a wide range of drugs, increased bioavailability, biocompatibility, patient compliance and sustained release characteristics [65]. The hydrogel microspheres were developed from the formulation of polyvinyl alcohol and Guar gum for controlled delivery of Nifedipine by emulsion cross-linking method for the treatment in severe hypertension [66].

Ray et al., developed an interpenetrating polymer network based on microspherical formulation from Sodium alginate and Polyvinyl alcohol by the emulsion cross-linking method in which Glutaraldehyde is used as a cross-linker. This IPN based formulation was used for the controlled release of Diclofenac Sodium [67]. Interpenetrating polymer network based microspheres was also used as a carrier for prolonged delivery of anti-cancer drug [3].

The rationale of developing mucoadhesive microspheres are that the formulation will be confined on the biological surface for localized delivery of the drug and the drug will be released close to the site of action with continuous enhancement of bioavailability [68]. IPN microspheres based on Xanthan gum and Polyvinyl alcohol were developed by emulsion cross-linked method to deliver the anti-inflammatory drug. In this formulation Glutaraldehyde is used as cross-linker [8].

Al-Kahtani AA et al., prepared semi-interpenetrating polymer network microspheres of chitosan-(dextran-g-acrylamide) by emulsion cross-linking method.

Glutaraldehyde was used as a cross-linking agent. Theophylline, an antiasthmatic drug was successfully incorporated into it by varying the ratio of dextran-g-acrylamide and amount of glutaraldehyde. The % encapsulation efficiency in between 50 and 78 was achieved. In-vitro release studies of theophylline from these matrices at pH 1.2 and 7.4 dissolution media demonstrated that slow release was extended up to18 hrs at 37°C [69]. Some of the IPN based microspheres with their applications are shown in Table 3.

Tablets: IPN can also be used for preparing an extended release matrix tablet from Chitosan / Carbapol inter-polymer complex. IPN based tablets are solid in nature and have great potential for anti-hypertensive action by blending with hydrophilic inter-polymer complexes or a hydrophobic waxy polymer [81]. Kulkarni et al., prepared IPN matrix tablets of sodium alginate and carrageenan for controlled release of Propranolol HCl. by wet granulation/covalent cross-linking method and subsequently compressed into tablets. The pure drug showed rapid and complete dissolution within 60 min but IPN based tablets showed slower and prolonged drug release over 18 h. The study concluded that the cross-linking time of granules affected the release of drug from IPN matrix [82]. Some of the IPN based tablets with their applications are shown in Table 4.

Sheet: Sheeting is one of the new method of producing IPN based drug delivery system [70]. These are mainly used in various types of wound dressings and scar management products [85]. An IPN composed of polymeric material like polyol (allyl carbonate) e.g. nouryset®200 and epoxy resin is developed by 70-95 parts by weight of polyol (allyl carbonate) by means of radical initiation and polymerizing partially or completely concurrently is an epoxy resin forming mixture composed of 10-90 weight % of aliphatic or cycloaliphatic epoxide and 90-10 weight % of polyol/anhydride adduct [86].

Sponges: IPN based sponges are also used as drug delivery system. They were mainly used in wound dressings and hemostyptics and also very helpful in the treatment of severe burns [87]. The advantages of collagen are-

a) Their capacity to easily take up large quantities of tissue exudates and provide smooth adherence to the wet wound bed with preservation of moist climate.

b) Its protection against mechanical harm and secondary bacterial infection.

Collagen also promotes growth and cellular mobility and hence, inflammatory cells can actively penetrate the porous scaffold. Due to this a highly vascularized granulation bed is formed which encourages the creation of new granulation tissue and epithelium on the wound [25]. Collagen-based materials can be produced into a three-dimensional sponge for use as a wound dressing and as a support for cell cultured skin components [88]. Some of the IPN based sponges with their applications are shown in Table 5.

Capsules: IPN based capsules are one of the important approach for delivery of drug. IPN capsules are also used as drug delivery systems for sustain release of drug. Interpenetrating polymer networks (IPNs) hydrogel capsules consists of polyacrylamide and polyvinyl alcohol for sustained drug release. Supracolloidal IPN reinforced capsules using micron‐sized colloidosomes of poly(methyl methacrylate‐co‐di-vinyl benzene) micro gels were used as scaffold via radical polymerization of the interior phase to produce hollow supracolloidal structures with a raspberry core-shell morphology [93]. Some of the IPN based capsules with their applications are shown in Table 6.

Biomedical Applications of IPN Based Drug Delivery System: Some of the biomedical applications of IPN based drug delivery systems with their applications are shown in Table 7.


It can be concluded from the whole literature survey that IPN based systems have wide applications in pharmaceuticals and medical sciences. IPN based polymeric materials can significantly change the release behavior of drug, protein/peptide, hormones and medicinal active agents. The study of IPN for drug delivery system may be helpful in understanding of critical diseases like acquired immune deficiency syndrome (AIDS), cancer and cardiac diseases as well as inflammatory diseases like rheumatoid arthritis, osteoarthritis and meningitis etc. IPN is mainly used as a carrier system for delivery of short biological half-life drugs. IPN has various advantages like excellent swelling capacity, specificity, and mechanical strength which play an important role in controlled and targeted drug delivery. Current study supports the theory that IPN can provide the resources to deliver the drugs at a prolonged controlled release for specific targets. IPN based biomaterials can serve as a potential candidate for tissue engineering and drug delivery system and are expected to become a useful matrix substance for various biomedical and therapeutic applications in the future.


The authors confirm that this article content has no conflict of interest.


Authors would like to thanks Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University and NISCAIR (National Institute of Science Communications and Information Resources), New Delhi for providing library facilities.


[1] Lohani A, Singh G, Bhattacharya SS, Verma A. Interpenetrating polymer networks as innovative drug delivery systems J Drug Deliv 2014; 2014: 583612.
[2] Singh P, Kumar SK, Keerthi TS, Mani TT, Getyala A. Interpenetrating polymer network (IPN) microparticles and advancement in novel drug delivery system: a review Pharm Sci Monitor 2012; 3(1): 1826-37.
[3] Patel JM, Savani HD, Turakhiya JM, Akbari BV, Goyani M, Raj HA. Interpenetrating polymer network (IPN): A noval approach for controlled drug delivery Uni J Pharm 2012; 01(01): 1-11.
[4] Rokhade AP, Patil SA, Aminabhavi TM. Synthesis and characterization of semi-interpenetrating microspheres of acrylamide grafted dextran and chitosan for controlled release of acyclovir Carbohydr Polym 2007; 67: 605-13.
[5] Margaret MT, Brahmaiah B, Krishna PV, Revathi B, Nama S. Interpenetrating polymer network (IPN) microparticles an advancement in novel drug delivery system: a review Int J Pharm Res Bio Sci 2013; 2(3): 215-24.
[6] Kudela V. “Hydrogels,” in encyclopedia of polymer science and engineering. New York, NY, USA: Wiley 1987; pp. 783-807.
[7] Work WJ, Horie K, Hess M, Stepto RF. Definitions of terms related to polymer blends, composites, and multiphase polymeric materials Pure Appl Chem 2004; 76(11): 1985-2007.
[8] Jain N, Sharma PK, Banik A, Gupta A, Bhardwaj V. Pharmaceutical and biomedical applications of interpenetrating polymer network Curr Drug Ther 2011; 6: 263-70.
[9] Banerjee S, Ray S, Maiti S, et al. Interpenetrating polymer network (IPN): A novel biomaterial Int J Appl Pharm 2010; 2(1): 28-34.
[10] Jain N, Banik A, Gupta A. Novel interpenetrating polymer network microspheres of lepidium sativum and poly (vinyl alcohol) for the controlled release of simvastatin Int J Pharm Pharm Sci 2013; 5(1): 125-30.
[11] Rokhade AP, Shelke NB, Patil SA, Aminabhavi TM. Novel interpenetrating polymer network microspheres of chitosan and methylcellulose for controlled release of theophylline Carbohydr Polym 2007; 69(4): 678-87.
[12] Kurokawa T, Gong JP. Super tough double network hydrogels and their application as biomaterials Polymer (Guildf) 2012; 53: 1805-22.
[13] Dave VJ, Patel HS. Synthesis and characterization of interpenetrating polymer networks from trans-esterified castor oil based polyurethane and polystyrene. J Saudi Chem Soc 2013.
[14] Jaisankar SN, Muralisankar R, Seeni MK, Mandal AB. Thermoplastic interpenetrating polymer networks based on polyvinyl chloride and polyurethane ionomers for damping application Soft Matter 2013; 11: 55-60.
[15] Athawale VD, Kolekar SL, Raut SS. Recent developments in polyurethanes and poly(acrylates) interpenetrating polymer networks J Macromol Sci Polymer Rev 2003; 43: 1-26.
[16] Vancaeyzeele C, Fichet O, Boileau S, Teyssie D. Polyisobutene-poly (methylmethacrylate) interpenetrating polymer networks: synthesis and characterization Polymer (Guildf) 2005; 46: 6888-96.
[17] Anzlovar A, Zigon M. Semi-interpenetrating polymer networks with varying mass ratios of functional urethane and methacrylate prepolymers Acta Chim Slov 2005; 52: 230-7.
[18] Merlin DL, Sivasankar B. Synthesis and characterization of semi-interpenetrating polymer networks using biocompatible polyurethane and acrylamide monomer Eur Polym J 2009; 45: 165-70.
[19] Wu X, He G, Gu S, Hu Z, Yao P. Novel interpenetrating polymer network sulfonated poly (phthalazinone ether sulfone ketone)/polyacrylic acid proton exchange membranes for fuel cell J Membr Sci 2007; 295: 80-7.
[20] Sperling LH. Interpenetrating polymer network and related materials. New York: Plenum Press 1981; Vol. 1: p. 265.
[21] Shidhaye S, Surve C, Dhone A, Budhkar T. Interpenetrating polymer network: An overview Int J Res Rev Pharmacy Appl Sci 2010; 2(4): 637-50.
[22] McNaught D, Wilkinson A. IUPAC compendium of chemical terminology (the "Gold Book") Oxford: Blackwell Scientific Publications 2007; 2(2): 1815 1815.
[23] Suresh PK, Suryawani SK, Dewangan D. Chitosan based interpenetrating polymer network (ipn) hydrogels: a potential multicomponent oral drug delivery vehicle. Pharmacie Globale Int J Comp Pharm 2011; 8(1): 1-8.
[24] Hou X, Siow KS. Novel interpenetrating polymer network electrolytes Elsev Polymer 2001; 42(9): 4181-8.
[25] Kim IY, Yoo MK, Seo JH, et al. Evaluation of semi-interpenetrating polymer networks composed of chitosan and poloxamer for wound dressing application Int J Pharm 2007; 341(1-2): 35-43.
[26] Rosenthal FM, Köhler G. Collagen as matrix for neo-organ formation by gene-transfected fibroblasts Anticancer Res 1997; 17(2A): 1179-86.
[27] Cascone MG, Sim B, Downes S. Blends of synthetic and natural polymers as drug delivery systems for growth hormone Biomaterials 1995; 16(7): 569-74.
[28] Ramaraj B, Radhakrishnan G. Hydrogel capsules for sustained drug release J Appl Polym Sci 1994; 51: 979-88.
[29] Park JC, Hwang YS, Lee JE, et al. Type I atelocollagen grafting onto ozone-treated polyurethane films: cell attachment, proliferation, and collagen synthesis J Biomed Mater Res 2000; 52(4): 669-77.
[30] Ward MA, Georgiou TK. Thermoresponsive polymers for biomedical applications Polymers (Basel) 2011; 3: 1215-42.
[31] Zakharchenko S, Puretskiy N, Stoychev G, Stamm M, Ionov L. Temperature controlled encapsulation and release using partially biodegradable thermo-magneto-sensitive self-rolling tubes Soft Matter 2010; 6: 2633-6.
[32] Thakur A, Monga S, Wanchoo RK. Sorption and drug release studies from semi-ipn of chitosan and xantham gum Chem Biochem Eng Q 2014; 28(1): 105-15.
[33] Mohanan A, Vishalakhi B. Swelling and diffusion characteristics of ipn films compound of naalg and gelatin: transport of Azure B Int J Polymer Mater Polymer Biomater 2009; 58(1): 561-80.
[34] Yue YM, Xu K, Liu XG, Chen Q, Sheng X, Wang PX. Preparation and characterization of interpenetration polymer network films based on poly(vinyl alcohol) and poly(acrylic acid) for drug delivery J Appl Polym Sci 2008; 108(6): 3836-42.
[35] Zhang K, Lian W, Liu S, Liu S. Multi-switchable bioelectrocatalysis based on semi-interpenetrating polymer network films prepared by enzyme-induced polymerization J Electrochem Soc 2014; 161(9): 493-500.
[36] Lu G, Yu HP, Zeng ZQ, Luo YY. Preparation and properties of interpenetrating polymer network films from prevulcanized natural rubber latex/chitosan blends Adv Mat Res 2011; 396-8: 400-6.
[37] Mayet N, Kumar P, Choonara YE, et al. Synthesis of a semi-interpenetrating polymer network as a bioactive curcumin film AAPS PharmSciTech 2014; 15(6): 1476-89.
[38] Honmute S, Ganachari SV, Bhat R, Kumar N, Huh DS, Venkataraman A. Studies on polyaniline-polyvinyl alcohol (pani-pva) interpenetrating polymer network (ipn) thin film Int J Sci Res 2012; 1(02): 102-6.
[39] Reddy TT, Takahara A. Simultaneous and sequential micro-porous semi-interpenetrating polymer network hydrogel films for drug delivery and wound dressing applications Polymer (Guildf) 2009; 50(15): 3537-46.
[40] Cui W, Tang D, Liu J, Yang F. Interfacial actions and adherence of an interpenetrating polymer network thin film on aluminum substrate J Surf Eng Mater Adv Technol 2011; 1: 89-94.
[41] Karaaslan MA, Tshabalala MA, Buschle-Diller G. Semi-interpenetrating polymer network hydrogels based on aspen hemicellulose and chitosan: effect of crosslinking sequence on hydrogel properties J Appl Polym Sci 2012; 124: 1168-77.
[42] Sakai Y, Sadaoka Y, Matsuguchi M, Hirayama K. Water resistive humidity sensor composed of interpenetrating polymer networks of hydrophilic and hydrophilic methacrylate Solid-State Sens Actuat 1991; 585(7): 562-5.
[43] Rodkate N, Wichai U, Boontha B, Rutnakornpituk M. Semi-interpenetrating polymer network hydrogels between polydimethylsiloxane/polyethylene glycol and chitosan Carbohydr Polym 2010; 81: 617-25.
[44] Kim SJ, Shin SR, Spinks GM, Kim IY, Kim SI. Synthesis and characteristics of a semi-interpenetrating polymer network based on chitosan/polyaniline under different ph conditions J Appl Polym Sci 2005; 96: 867-73.
[45] Bhardwaj V, Harit G, Kumar S. Interpenetrating polymer network (IPN): novel approach in drug delivery Int J Drug Develop Res 2012; 4(3): 41-54.
[46] Peppas NA, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations Eur J Pharm Biopharm 2000; 50(1): 27-46.
[47] Zhao Y, Kang J, Tan TW. Salt, pH and temperature responsive semi-interpenetrating polymer network hydrogel based on poly (aspartic acid) and poly (acrylic acid) Polymer (Guildf) 2006; 47(22): 7702-10.
[48] Lohani A, Singh G, Bhattacharya SS, Verma A. Interpenetrating polymer networks as innovative drug delivery systems J Drug Deliv 2014; 2014: 583612.
[49] Suri S, Schmidt CE. Photopatterned collagen-hyaluronic acid interpenetrating polymer network hydrogels Acta Biomater 2009; 5(7): 2385-97.
[50] Naficy S, Kawakami S, Sadeghovaad S, Wakisaka M, Spinks GM. Mechanical properties of interpenetrating polymer network hydrogels based on hybrid ionically and covalently crosslinked networks J Appl Polym Sci 2013; 130(4): 2504-13.
[51] Ray R, Maity S, Mandal S, Chatterjee TK, Sa B. Studies on the release of ibuprofen from al3+ ion cross-linked homopolymeric and interpenetrating network hydrogel beads of carboxymethyl xanthan and sodium alginate Adv Polym Technol 2011; 30(1): 1-11.
[52] Hago EE, Li X. Interpenetrating polymer network hydrogels based on gelatin and pva by biocompatible approaches: synthesis and characterization. Adv Mater Sci Engin 2013; pp. 1-8.
[53] Vaghani SS, Patel MM. pH-sensitive hydrogels based on semi-interpenetrating network (semi-IPN) of chitosan and polyvinyl pyrrolidone for clarithromycin release Drug Dev Ind Pharm 2011; 37(10): 1160-9.
[54] Gupta NV, Satish CS, Shivakumar HG. Preparation and characterization of gelatin-poly(methacrylic acid) interpenetrating polymeric network hydrogels as a ph-sensitive delivery system for glipizide Indian J Pharm Sci 2007; 69(01): 64-8.
[55] Gupta AK, Maurya SD, Dhakar RC, Singh RD. pH sensitive interpenetrating hydrogel for eradication of helicobacter pylori Int J Pharm Sci Nanotechnol 2010; 3(2): 924-32.
[56] Maiti S, Chowdhary M, Chakraborty A, Ray S, Sa B. Sulfated locust bean gum hydrogel beads for immediates analgesics effects of tramadol hydrochloride J Sci Ind Res 2014; 73: 21-8.
[57] Kim SJ, Shin SR, Kim NG, Kim SI. Swelling behavior of semi‐interpenetrating polymer network hydrogels based on chitosan and poly(acryl amide) J Macromol Sci Part A Pure Appl Chem 2005; 42(8): 1073-83.
[58] Prabhakar MN, Rao US, Babu PK, Subha MC, Rao KC. Interpenetrating polymer network hydrogel membranes of PLA and SA for control release of penicillamine drug Ind J Adv Chem Sci 2013; 1(4): 240-9.
[59] Kim SJ, Lee CK, Kim IY, Kim SI, Kim NG. Water sorption of interpenetrating polymer network hydrogels composed of poly (ethylene oxide) and poly (methyl methacrylate) High Perform Polym 2004; 16(4): 515-23.
[60] Xue Y, Xuegang L, Benchao H. Preparation and characterization of interpenetrating polymer network hydrogels based on konjac glucomannan with various molecular weights and poly (acrylic acid) for controlled release Chem Ind Eng Prog 2013; 31(1): 151-5.
[61] Gupta NV, Shivakumar HG. Interpenetrating network superporous hydrogels for gastroretentive application-preparation, swelling and mechanical properties Turk J Pharm Sci 2012; 9(2): 127-38.
[62] Qiu Y, Park K. Superporous IPN hydrogels having enhanced mechanical properties AAPS PharmSciTech 2003; 4(4): E51.
[63] Lohani A, Gangwar PC. Mucoadhesion: a novel approach to increase gastroretention Chronicl Young Sci 2013; 3: 121-8.
[64] Swapna S, Balaji A, Shankar MS, Vijendar A. Microspheres as a promising mucoadhesive drug delivery system-review Int J Pharm Sci Rev Res 2013; 23(2): 8-14.
[65] Bhattacharya SS, Mazahir F, Banerjee S, Verma A, Ghosh A. Preparation and in vitro evaluation of xanthan gum facilitated superabsorbent polymeric microspheres Carbohydr Polym 2013; 98(1): 64-72.
[66] Soppimath KS, Kulkarni AR, Aminabhavi TM. Controlled release of antihypertensive drug from the interpenetrating network poly(vinyl alcohol)-guar gum hydrogel microspheres J Biomater Sci Polym Ed 2000; 11(1): 27-43.
[67] Ray S, Maiti S, Banerjee S, et al. Interpenetrating polymer network (IPN): a novel biomaterial Int J Appl Pharm 2010; 2(1): 28-34.
[68] Alexander A, Tripathi DK, Verma T, Maurya J, Patel S. Mechanism responsible for mucoadhesion of mucoadhesive drug delivery system: a review Int J Appl Biol Pharm Technol 2011; 2(1): 434-45.
[69] Al-Kahtani AA, Sherigara BS. Controlled release of theophylline through semi-interpenetrating network microspheres of chitosan-(dextran-g-acrylamide) J Mater Sci Mater Med 2009; 20(7): 1437-45.
[70] Banerjee S, Chaurasia G, Pal DK, Ghosh AK, Ghosh A, Kaity S. Investigation on cross-linking density for development of novel interpenetrating polymer network (IPN) based formulation J Sci Ind Res 2010; 69: 777-84.
[71] Mundargi RC, Shelke NB, Babu VR, Patel P, Rangaswamy V, Aminabhavi TM. Novel thermo-responsive semi-interpenetrating network microspheres of gellan gum-poly (N-isopropylacrylamide) for controlled release of atenolol J Appl Polym Sci 2010; 116(3): 1832-41.
[72] Solak EK. Preparation and characterization of ipn microspheres for controlled delivery of naproxen J Biomater Nanobiotechnol 2011; 2: 445-53.
[73] Angadi SC, Manjeshwar LS, Aminabhavi TM. Interpenetrating polymer network blend microspheres of chitosan and hydroxyethyl cellulose for controlled release of isoniazid Int J Biol Macromol 2010; 47(2): 171-9.
[74] Prasad CV, Reedy CLN, Mallikarjuna B, Rao KC, Subha MCS. Interpenetrating polymer network microspheres of hydroxyl propyl methyl cellulose/poly (vinyl alcohol) for control release of ciprofloxacin hydrochloride Cellulose 2011; 18: 349-57.
[75] Ramakrishna P, Rao KM, Sekharnath KV, et al. Synthesis and characterization of Interpenetrating polymer network microspheres of acryl amide grafted carboxy methylcellulose and sodium alginate for controlled release of triprolidine hydrochloride monohydrate J Appl Pharm Sci 2013; 3(3): 101-8.
[76] Banerjee S, Siddiqui L, Bhattacharya SS, et al. Interpenetrating polymer network (IPN) hydrogel microspheres for oral controlled release application Int J Biol Macromol 2012; 50(1): 198-206.
[77] Angadi SC, Manjeshwar LS, Aminabhavi TM. Stearic acid-coated chitosan-based interpenetrating polymer network microspheres: controlled release characteristics Ind Eng Chem Res 2011; 50(8): 4504-14.
[78] Kassem AA, Marzouk MA, El-Adawy SA, Dawaba AM. Formulation, in-vitro and in-vivo evaluation of semi-interpenetrating polymer network (Semi-IPN) microspheres of ketorolac tromethamine J Life Med 2013; 1(3): 48-54.
[79] Sekhar EC, Rao KS, Raju RR. Chitosan/guar-gum-g-acrylamide semi IPN microspheres for controlled release studies of 5-Fluorouracil J Appl Pharm Sci 2011; 01(08): 199-204.
[80] Bhardwaj V, Kumar S. Design and characterization of novel interpenetrating polymer network mucoadhesive microspheres of locust bean gum and pva for controlled release of metformin HCl Int Pharm Sci 2012; 2(2): 115-21.
[81] Abdelbary GA, Tadros MI. Design and in vitro/in vivo evaluation of novel nicorandil extended release matrix tablets based on hydrophilic interpolymer complexes and a hydrophobic waxy polymer Eur J Pharm Biopharm 2008; 69(3): 1019-28.
[82] Kulkarni RV, Baraskar VV, Setty CM, Sa B. Interpenetrating polymer network matrices of sodium alginate and carrageenan for controlled drug delivery application Fiber Polymer 2011; 12: 352-8.
[83] Mandal S, Basu SK, Sa B. Ca2+ ion cross-linked interpenetrating network matrix tablets of polyacrylamide-grafted-sodium alginate and sodium alginate for sustained release of diltiazem hydrochloride Carbohydr Polym 2010; 82: 867-73.
[84] Kulkarnia RV, Baraskar VV, Alange VV, Naikawadi AA, Sa B. Controlled release of an antihypertensive drug through interpenetrating polymer network hydrogel tablets of tamarind seed polysaccharide and sodium alginate J Macromol Sci 2013; 52(11): 1636-50.
[85] Schutyser JA, Boonstra TO. Schutyser JAJ, Boonstra TO Interpenetrating polymer network of an aliphatic polyol(allyl carbonate) and epoxy resin US Patent 1990.
[86] Dillon ME. Process for the manufacture of interpenetrating polymer network sheeting and useful articles thereof US Patent 2006.
[87] Chvapil M. Considerations on manufacturing principles of a synthetic burn dressing: a review J Biomed Mater Res 1982; 16(3): 245-63.
[88] Doillon CJ. Porous collagen sponge wound dressings: in vivo and in vitro studies J Biomater Appl 1988; 2(4): 562-78.
[89] Lefebvre F, Gorecki S, Bareille R, Amedee J, Bordenave L, Rabaud M. New artificial connective matrix-like structure made of elastin solubilized peptides and collagens: elaboration, biochemical and structural properties Biomaterials 1992; 13(1): 28-33.
[90] Doillon CJ, Silver FH. Collagen-based wound dressing: effects of hyaluronic acid and fibronectin on wound healing Biomaterials 1986; 7(1): 3-8.
[91] Lefebvre F, Pilet P, Bonzon N, Daculsi G, Rabaud M. New preparation and microstructure of the EndoPatch elastin-collagen containing glycosaminoglycans Biomaterials 1996; 17(18): 1813-8.
[92] Prajapati RT, Chavally-Mis B, Herbage D, Eastwood M, Brown RA. Mechanical loading regulates protease production by fibroblasts in three-dimensional collagen substrates Wound Repair Regen 2000; 8(3): 226-37.
[93] Stefan AF, Bon SC, Colver PJ. Colloidosomes as micron‐sized polymerisation vessels to create supracolloidal interpenetrating polymer network reinforced capsules Soft Mater 2007; 3: 194-9.
[94] Ramaraj B, Radhakrishnan G. Hydrogel capsules for sustained drug release J Appl Polym Sci 1994; 51: 979-88.
[95] Clarke KM, Lantz GC, Salisbury SK, Badylak SF, Hiles MC, Voytik SL. Intestine submucosa and polypropylene mesh for abdominal wall repair in dogs Curr Drug Ther 2011; 6(4): 269.
[96] Jain N, Banik A. Novel interpenetrating polymer network mucoadhesive microspheres of gum ghatti and poly (vinyl alcohol) for the delivery of ranitidine HCl Asi J Pharm Clin Res 2013; 6(1): 119-23.
[97] Barber TA, Ho JE, De Ranieri A, Virdi AS, Sumner DR, Healy KE. Peri-implant bone formation and implant integration strength of peptide-modified p(AAM-co-EG/AAC) interpenetrating polymer network-coated titanium implants J Biomed Mater Res A 2007; 80(2): 306-20.
[98] Yin L, Ding J, Fei L, et al. Beneficial properties for insulin absorption using superporous hydrogel containing interpenetrating polymer network as oral delivery vehicles Int J Pharm 2008; 350(1-2): 220-9.
[99] Tiğli RS, Gümüşderelioğlu M. Evaluation of alginate-chitosan semi IPNs as cartilage scaffolds J Mater Sci Mater Med 2009; 20(3): 699-709.
[100] George J, Onodera J, Miyata T. Biodegradable honeycomb collagen scaffold for dermal tissue engineering J Biomed Mater Res A 2008; 87(4): 1103-11.
[101] Dandangi PM, Mastiholimath VS, Gadad AP, Iliger SR. Mucoadhesive microsphere of propanol HCl for nasal delivery Int J Pharm Sci 2007; 69(3): 402-7.
[102] Kumari K, Kundu PP. Semi-Interpenetrating polymer networks (IPNs) of chitosan and L-alanine for monitoring the release of chlorpheniramine maleate J Appl Polym Sci 2007; 103(6): 3751-7.
[103] Auger FA, Rouabhia M, Goulet F, Berthod F, Moulin V, Germain L. Tissue-engineered human skin substitutes developed from collagen-populated hydrated gels: clinical and fundamental applications Med Biol Eng Comput 1998; 36(6): 801-12.
[104] Shanmugasundaram N, Ravichandran P, Reddy PN, Ramamurty N, Pal S, Rao KP. Collagen-chitosan polymeric scaffolds for the in vitro culture of human epidermoid carcinoma cells Biomaterials 2001; 22(14): 1943-51.
[105] Kim IY, Yoo MK, Kim BC, Kim SK, Lee HC, Cho CS. Preparation of semi-interpenetrating polymer networks composed of chitosan and poloxamer Int J Biol Macromol 2006; 38(1): 51-8.
[106] Takaoka K, Nakahara H, Yoshikawa H, Masuhara K, Tsuda T, Ono K. Ectopic bone induction on and in porous hydroxyapatite combined with collagen and bone morphogenetic protein Clin Orthop Relat Res 1988; (234): 250-4.
[107] Risbud MV, Hardikar AA, Bhat SV, Bhonde RR. pH-sensitive freeze-dried chitosan-polyvinyl pyrrolidone hydrogels as controlled release system for antibiotic delivery J Control Release 2000; 68(1): 23-30.
[108] Liu L, Zhang L, Ren B, Wang F, Zhang Q. Preparation and characterization of collagen-hydroxyapatite composite used for bone tissue engineering scaffold Artif Cells Blood Substit Immobil Biotechnol 2003; 31(4): 435-48.
[109] Moullier P, Maréchal V, Danos O, Heard JM. Continuous systemic secretion of a lysosomal enzyme by genetically modified mouse skin fibroblasts Transplantation 1993; 56(2): 427-32.
[110] Rao KS, Naidu BV, Subha MC, Sairam M, Aminabhavi TM. Novel chitosan-based pH-sensitive interpenetrating network microgels for the controlled release of cefadroxil Carbohydr Polym 2006; 66: 333-44.
[111] Myung D, Farooqui N, Zheng LL, et al. Bioactive interpenetrating polymer network hydrogels that support corneal epithelial wound healing J Biomed Mater Res A 2009; 90(1): 70-81.
[112] Bhatt N, Bhatt G, Kothiyal P. pH-responsive semi-interpenetrating polymeric hydrogels microspheres of chitosan and poly vinyl alcohol for in-vitro controlled release of clarithromycin Int J Pharmacother 2014; 4(2): 68-73.
[113] Mallikarjuna B, Rao KM, Sudhakar P, Rao KC, Subha MC. Chitosan based biodegradable hydrogel microspheres for controlled release of an Anti-HIV drug J Adv Chem Sci 2013; 1(3): 144-51.
[114] Steffensen SL, Vestergaard MH, Møller EH, et al. Soft hydrogels interpenetrating silicone-A polymer network for drug-releasing medical devices J Biomed Mater Res B Appl Biomater 2015; 00B(00): 1-9.