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Accelerated wound healing and anti-inflammatory effects of physically cross linked polyvinyl alcohol–chitosan hydrogel containing honey bee venom in diabetic rats

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Abstract

Diabetes is one of the leading causes of impaired wound healing. The objective of this study was to develop a bee venom-loaded wound dressing with an enhanced healing and anti-inflammatory effects to be examined in diabetic rats. Different preparations of polyvinyl alcohol (PVA), chitosan (Chit) hydrogel matrix-based wound dressing containing bee venom (BV) were developed using freeze–thawing method. The mechanical properties such as gel fraction, swelling ratio, tensile strength, percentage of elongation and surface pH were determined. The pharmacological activities including wound healing and anti-inflammatory effects in addition to primary skin irritation and microbial penetration tests were evaluated. Moreover, hydroxyproline, glutathione and IL-6 levels were measured in the wound tissues of diabetic rats. The bee venom-loaded wound dressing composed of 10 % PVA, 0.6 % Chit and 4 % BV was more swellable, flexible and elastic than other formulations. Pharmacologically, the bee venom-loaded wound dressing that has the same pervious composition showed accelerated healing of wounds made in diabetic rats compared to the control. Moreover, this bee venom-loaded wound dressing exhibited anti-inflammatory effect that is comparable to that of diclofenac gel, the standard anti-inflammatory drug. Simultaneously, wound tissues covered with this preparation displayed higher hydroxyproline and glutathione levels and lower IL-6 levels compared to control. Thus, the bee venom-loaded hydrogel composed of 10 % PVA, 0.6 % Chit and 4 % BV is a promising wound dressing with excellent forming and enhanced wound healing as well as anti-inflammatory activities.

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References

  • Abdulla, M.A., K.A. Ahmed, H.M. Ali, S.M. Noor, and S. Ismail. 2009. Wound healing activities of Rafflesia hasseltii extract in rats. Journal of Clinical Biochemistry and Nutrition 45: 304–308.

    Article  PubMed Central  PubMed  Google Scholar 

  • Ajji, Z., I. Othman, and J.M. Rosiak. 2005. Production of hydrogel wound dressing using gamma radiation. Nuclear instruments & methods in physics research. Section B 229: 375–380.

    Article  CAS  Google Scholar 

  • Alnahdi, H.S. 2012. Effect of Rosmarinus officinalis extract on some cardiac enzymes of streptozotocin-induced diabetic rats. Journal of Health Sciences 2: 33–37.

    Google Scholar 

  • Amin, M.A., I.T. Abdel-Raheem, and H.R. Madkor. 2008. Wound healing and anti-inflammatory activities of bee venom-chitosan blend films. Journal of Drug Delivery Science and Technology 18: 424–430.

    CAS  Google Scholar 

  • Asai, J., H. Takenaka, S. Hirakawa, J. Sakabe, A. Hagura, S. Kishimoto, K. Maruyama, K. Kajiya, S. Kinoshita, Y. Tokura, and N. Katoh. 2012. Topical simvastatin accelerates wound healing in diabetes by enhancing angiogenesis and lymphangiogenesis. American Journal of Pathology 181: 2217–2224.

    Article  CAS  PubMed  Google Scholar 

  • Balakrishnan, B., M. Mohanty, P.R. Umashankar, and A. Jayakrishnan. 2005. Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomaterials 26: 6335–6342.

    Article  CAS  PubMed  Google Scholar 

  • Belhekar, S.N., P.D. Chaudhari, J.S. Saryawanshi, K.K. Mali, and R.B. Pandhare. 2013. Antidiabetic and antihyperlipidemic effects of Thespesia populnea fruit pulp extracts on alloxan-induced diabetic rats. Indian Journal of Pharmaceutical Sciences 75: 217–221.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Berger, J., M. Reist, J.M. Mayer, O. Felt, and R. Gurnyb. 2004. Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications. European Journal of Pharmaceutics and Biopharmaceutics 57: 35–52.

    Article  CAS  PubMed  Google Scholar 

  • Bonferoni, M.C., P. Giunchedi, S. Scalia, S. Rossi, G. Sandri, and C. Caramella. 2006. Chitosan gels for the vaginal delivery of lactic acid: relevance of formulation parameters to mucoadhesion and release mechanisms. American Association of Pharmaceutical Scientists 7: 104–110.

    Article  Google Scholar 

  • Cárdenas, G., P. Anaya, C. Von Plessing, C. Rojas, and J. Sepúlveda. 2008. Chitosan composite films. Biomedical applications. Journal of Materials Science. Materials in Medicine 19: 2397–2405.

    Article  PubMed  Google Scholar 

  • Cascone, M.G., S. Maltinti, and N. Barbani. 1999. Effect of chitosan and dextran on the properties of poly (vinyl alcohol) hydrogels. Journal of Materials Science. Materials in Medicine 10: 431–435.

    Article  CAS  PubMed  Google Scholar 

  • Choi, Y.S., S.R. Hong, Y.M. Lee, K.W. Song, M.H. Park, and Y.S. Nam. 1999. Study on gelatin-containing artificial skin: I. Preparation and characteristics of novel gelatin-alginate sponge. Biomaterials 20: 409–417.

    Article  CAS  PubMed  Google Scholar 

  • Chung, L.Y., R.J. Schmidt, P.F. Hamlyn, B.F. Sagar, A.M. Andrews, and T.D. Turner. 1994. Biocompatibility of potential wound management products: fungal mycelia as a source of chitin/chitosan and their effect on the proliferation of human F1000 fibroblasts in culture. Journal of Biomedical Materials Research 28: 463–469.

    Article  CAS  PubMed  Google Scholar 

  • Clark, R.F. 2008. Oxidative stress and “senescent” fibroblasts in non-healing wounds as potential therapeutic targets. Journal of Investigative Dermatology 128: 2361–2364.

    Article  CAS  PubMed  Google Scholar 

  • De Jong, S.J., B. Van Eerdenbrugh, C.F. Van Nostrum, J.J. Kettenes-Van Den Bosch, and W.E. Hennink. 2001. Physically rosslinked dextran hydrogels by stereocomplex formation of lactic acid oligomers: Degradation and protein release behavior. Journal of Control Release 71: 261–275.

    Article  Google Scholar 

  • Değim, Z., N. Celebi, H. Sayan, A. Babül, D. Erdoğan, and G. Take. 2002. An investigation on skin wound healing in mice with a taurine-chitosan gel formulation. Amino Acids 22: 187–198.

    Article  PubMed  Google Scholar 

  • Demling, R.H. 2000. Oxandrolone, an anabolic steroid, enhances the healing of cutaneous wound in the rat. Wound Repair and Regeneration 8: 97–102.

    Article  CAS  PubMed  Google Scholar 

  • Diplock, A.T. 1994. In Antioxidants and Free Radicals Scavengers: Free Radical Damage and Its Control, ed. C.A. Rice-Evans, and R.H. Burdon, 43–49. Amsterdam: Elsevier.

    Google Scholar 

  • Drucker, M., E. Cardenas, P. Azitri, A. Valenzuela, and A. Gamboa. 1998. Experimental studies on effect of lidocaine on wound healing. World Journal of Surgery 22: 394–398.

    Article  CAS  PubMed  Google Scholar 

  • Durmus, M., E. Karaaslan, E. Ozturk, M. Gulec, M. Iraz, N. Edali, and M.O. Ersoy. 2003. The effects of single-dose dexamethasone on wound healing in rats. Anesthesia and Analgesia 97: 1377–1380.

    Article  CAS  PubMed  Google Scholar 

  • Dutta, J. 2012. Synthesis and Characterization of γ-irradiated PVA/PEG/CaCl2 Hydrogel for Wound Dressing. Journal of the American Chemical Society 2: 6–11.

    Article  CAS  Google Scholar 

  • Ellman, G.L. 1959. Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics 82: 70–77.

    Article  CAS  PubMed  Google Scholar 

  • Ge, J., Y. Cui, Y. Yan, and W. Jiang. 2000. The effect of structure on pervapouration of 498 chitosan membrane. Journal of Membrane Science 165: 75–81.

    Article  CAS  Google Scholar 

  • Hargreaves, K., R. Dubner, F. Brown, C. Flores, and J. Joris. 1988. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32: 77–88.

    Article  CAS  PubMed  Google Scholar 

  • Hassan, C.M., and N.A. Peppas. 2000. Structure and morphology of freeze/thawed PVA hydrogels. Macromolecules 33: 2472–2479.

    Article  CAS  Google Scholar 

  • Hassanein, N.M., and A.M. Hegab. 2010. Bee venom–lead acetate toxicity interaction. Australian Journal of Basic and Applied Sciences 4: 2206–2221.

    CAS  Google Scholar 

  • Hennink, W.E., and C.F. Van Nostrum. 2002. Novel cross-linking methods to design hydrogels. Advanced Drug Delivery Reviews 54: 13–36.

    Article  CAS  PubMed  Google Scholar 

  • Hennink, W.E., S.J. De Jong, G.W. Bos, T.F. Veldhuis, and C.F. Van Nostrum. 2004. Biodegradable dextran hydrogels crosslinked by stereocomplex formation for the controlled release of pharmaceutical proteins. International Journal of Pharmaceutics 277: 99–104.

    Article  CAS  PubMed  Google Scholar 

  • Hider, R.C. 1988. Honeybee venom: a rich source of pharmacologically active peptides. Endeavour 12: 60–65.

    Article  CAS  PubMed  Google Scholar 

  • Huang, M.H., and M.C. Yang. 2008. Evaluation of glucan/poly (vinyl alcohol) blend wound dressing using rat models. International Journal of Pharmaceutics 346: 38–46.

    Article  CAS  PubMed  Google Scholar 

  • Ishihara, M., K. Ono, M. Sato, K. Nakanishi, Y. Saito, H. Yura, T. Matsui, H. Hattori, M. Fujita, M. Kikuchi, and A. Kurita. 2001. Acceleration of wound contraction and healing with a photocrosslinkable chitosan hydrogel. Wound Repair and Regeneration 9: 513–521.

    Article  CAS  PubMed  Google Scholar 

  • Khatun, U.L., and C. Mukhopadhyay. 2013. Interaction of bee venom toxin melittin with ganglioside GM1 bicelle. Biophysical Chemistry 180–181: 66–75.

    Article  PubMed  Google Scholar 

  • Kim, I.Y., M.K. Yoo, B.C. Kim, S.K. Kim, H.C. Lee, and C.S. Cho. 2006. Preparation of semi- interpenetrating polymer networks composed of chitosan and poloxamer. International Journal of Biological Macromolecules 38: 51–58.

    Article  CAS  PubMed  Google Scholar 

  • Kim, J.O., J.K. Park, J.H. Kim, S.G. Jin, C.S. Yong, D.X. Li, J.Y. Choi, J.S. Woo, B.K. Yoo, W.S. Lyoo, J.A. Kim, and H.G. Choi. 2008. Development of polyvinyl alcohol–sodium alginate gel-matrix-based wound dressing system containing nitrofurazone. International Journal of Pharmaceutics 359: 79–86.

    Article  CAS  PubMed  Google Scholar 

  • Kim, S.H., S.Y. Jung, K.W. Lee, S.H. Lee, M. Cai, S.M. Choi, and E.J. Yang. 2013. Bee venom effects on ubiquitin proteasome system in hSOD1G85R-expressing NSC34 motor neuron cells. BMC Complementary and Alternative Medicine 13: 179–186.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kita, M., Y. Ogura, Y. Honda, S.H. Hyon, W. Cha, and Y. Ikada. 1990. Evaluation of polyvinyl alcohol hydrogel as a soft contact lens material. Graefes Archive for Clinical and Experimental Ophthalmology 228: 533–537.

    Article  CAS  Google Scholar 

  • Kiyama, T., D.T. Efron, U. Tantry, and A. Barbul. 2001. Trauma and wound healing: role of the route of nutritional support. International Journal of Surgical Investigation 2: 483–489.

    CAS  PubMed  Google Scholar 

  • Komi-Kuramochi, A., M. Kawano, Y. Oda, M. Asada, M. Suzuki, J. Oki, and T. Imamura. 2005. Expression of fibroblast growth factors and their receptors during full-thickness skin wound healing in young and aged mice. Journal of Endocrinology 186: 273–289.

    Article  CAS  PubMed  Google Scholar 

  • Koyano, T., N. Minoura, M. Nagura, and K. Kobayashi. 1998. Attachment and growth of cultured fibroblast cells on PVA/chitosan-blended hydrogels. Journal of Biomedical Materials Research 39: 486–490.

    Article  CAS  PubMed  Google Scholar 

  • Kwon, Y.B., H.J. Lee, H.J. Han, W.C. Mar, S.K. Kang, O.B. Yoon, A.J. Beitz, and J.H. Lee. 2002. The water-soluble fraction of bee venom produces antinociceptive and anti-inflammatory effects on rheumatoid arthritis in rats. Life Sciences 71: 191–204.

    Article  CAS  PubMed  Google Scholar 

  • Lee, Y.H., J.J. Chang, C.T. Chien, M.C. Yang, and H.F. Chien. 2012. Antioxidant sol-gel improves cutaneous wound healing in streptozotocin-induced diabetic rats. Experimental Diabetes Research 2012: 1–11.

    Google Scholar 

  • Li, X., S. Chen, B. Zhang, M. Li, K. Diao, Z. Zhang, J. Li, Y. Xu, X. Wang, and H. Chen. 2012a. In situ injectable nano-composite hydrogel composed of curcumin, N, O-carboxymethyl chitosan and oxidized alginate for wound healing application. International Journal of Pharmaceutics 437: 110–119.

    Article  CAS  PubMed  Google Scholar 

  • Li, X., K. Nan, L. Li, Z. Zhang, and H. Chen. 2012b. In vivo evaluation of curcumin nanoformulation loaded methoxy poly(ethylene glycol)-graft-chitosan composite film for wound healing application. Carbohydrate Polymers 88: 84–90.

    Article  CAS  Google Scholar 

  • Lin, S., N. Sangaj, T. Razafiarison, C. Zhang, and S. Varghese. 2011. Influence of Physical Properties of Biomaterials on Cellular Behavior. Pharmaceutical Research 28: 1422–1430.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lin, W.C., D.G. Yu, and M.C. Yang. 2006. Blood compatibility of novel PGA (poly glutamic acid)/poly vinyl alcohol hydrogels. Colloids and Surfaces B 47: 43–49.

    Article  CAS  Google Scholar 

  • Liu, H., Y. Du, X. Wang, and L. Sun. 2004. Chitosan kills bacteria through cell membrane damage. International Journal of Food Microbiology 95: 147–155.

    Article  CAS  PubMed  Google Scholar 

  • Loughlin, R.G., M.M. Tunney, R.F. Donnelly, D.J. Murphy, M. Jenkins, and P.A. Mccarron. 2008. Modulation of gel formation and drug-release characteristics of lidocaine-loaded poly(vinyl alcohol)-tetraborate hydrogel systems using scavenger polyol sugars. European Journal of Pharmaceutics and Biopharmaceutics 69: 1135–1146.

    Article  CAS  PubMed  Google Scholar 

  • Lozinsky, V.I., A.L. Zubov, V.K. Kulakova, E.F. Titova, and S.V. Rogozhin. 1992. Study of cryostructurization of polymer systems. IX: Poly (vinyl alcohol) cryogels filled with particles of crosslinked dextran gel. Journal of Applied Polymer Science 44: 1423–1435.

    Article  Google Scholar 

  • Maruyama, N., H. Ishibashi, W. Hu, S. Morofuji, S. Inouye, H. Yamaguchi, and S. Abe. 2006. Suppression of carrageenan- and collagen II-induced inflammation in mice by geranium oil. Mediators of Inflammation 2006: 62537–62540.

    Article  PubMed Central  PubMed  Google Scholar 

  • Mathieu, D., J.C. Linke, and F. Wattel. 2006. Non-healing wounds. In Handbook on hyperbaric medicine, ed. DE Mathieu, 401–427. Netherlands: Springer.

    Chapter  Google Scholar 

  • Molina, I., L. Suming, B. Martinez, and M. Vert. 2001. Protein release from physically cross-linked hydrogels of the PLA/PEO/PLA triblock copolymer-type. Biomaterials 22: 363–369.

    Article  CAS  PubMed  Google Scholar 

  • Morton, J.J., and M.H. Malone. 1972. Evaluation of vulneray activity by an open wound procedure in rats. Archives Internationales de Pharmacodynamie et de Therapie 196: 117–126.

    CAS  PubMed  Google Scholar 

  • Park, H.J., S.H. Lee, D.J. Son, K.W. Oh, K.H. Kim, H.S. Song, G.J. Kim, G.T. Oh, D.Y. Yoon, and J.T. Hong. 2004. Antiarthritic effect of bee venom: inhibition of inflammation mediator generation by suppression of NF-kappaB through interaction with the p50 subunit. Arthritis and Rheumatism 50: 3504–3515.

    Article  CAS  PubMed  Google Scholar 

  • Peh, K., T. Khan, and H. Chang. 2000. Mechanical, bioadhesive strength and biological evaluations of chitosan films for wound dressing. The Journal of Pharmaceutical Sciences 3: 303–311.

    CAS  Google Scholar 

  • Peppas, N.A., and P.A. Buri. 1985. Surface, interfacial and molecular aspects of polymer bioadhesion on soft tissues. Journal of Control Release 2: 257–275.

    Article  CAS  Google Scholar 

  • Peppas, N.A. 1987. Hydrogels in medicine in pharmacy, 1–48. Boca Raton: CRC Press.

    Google Scholar 

  • Peppas, N.A., and S.R. Stauffer. 1991. Reinforced uncrosslinked poly(vinyl alcohol) gels produced by cyclic freezing–thawing processes: a short review. Journal of Control Release 16: 305–310.

    Article  CAS  Google Scholar 

  • Peppas, N.A., and J.E. Scott. 1992. Controlled release from poly(vinyl alcohol) gels prepared by freeze–thawing processes. Journal of Control Release 18: 95–100.

    Article  CAS  Google Scholar 

  • Poon, A., and J. Sawynok. 1999. Antinociceptive and anti-inflammatory properties of an adenosine kinase inhibitor and an adenosine deaminase inhibitor. European Journal of Pharmacology 384: 123–138.

    Article  CAS  PubMed  Google Scholar 

  • Prockop, D.J., and K.I. Kivirikko. 1995. Collagens: molecular biology, diseases, and potential for therapy. Annual Review of Biochemistry 64: 403–434.

    Article  CAS  PubMed  Google Scholar 

  • Rabea, E.I., M.E. Badawy, C.V. Stevens, G. Smagghe, and W. Steurbaut. 2003. Chitosan as antimicrobial agent: applications and mode of action. Biomacromolecules 4: 1457–1465.

    Article  CAS  PubMed  Google Scholar 

  • Raghuraman, H., and A. Chattopadhyay. 2007. Melittin: a membrane-active peptide with diverse functions. Bioscience Reports 27: 189–223.

    Article  CAS  PubMed  Google Scholar 

  • Razzak, M.T., D. Darmawan, and S. Zainuddin. 2001. Irradiation of polyvinyl alcohol and polyvinyl pyrrolidone blended hydrogel for wound dressing. Radiation Physics and Chemistry 62: 107–113.

    Article  CAS  Google Scholar 

  • Roller, S., S. Sagoo, R. Board, T. O’mahony, E. Caplice, G. Fitzgerald, M. Fogden, M. Owen, and H. Fletcher. 2002. Novel combinations of chitosan, carnocin and sulphite for the preservation of chilled pork sausages. Meat Science 62: 165–177.

    Article  CAS  PubMed  Google Scholar 

  • Sarukawa, J., M. Takahashi, M. Abe, D. Suzuki, S. Tokura, T. Furuike, and H. Tamura. 2011. Effects of chitosan-coated fibers as a scaffold for three-dimensional cultures of rabbit fibroblasts for ligament tissue engineering. Journal of Biomaterials Science, Polymer Edition 22: 717–732.

    Article  CAS  Google Scholar 

  • Seo, S.W., W.S. Jung, S.E. Lee, C.M. Choi, B.C. Shin, E.K. Kim, K.B. Kwon, S.H. Hong, K.J. Yun, R.K. Park, M.K. Shin, H.J. Song, and S.J. Park. 2008. Effects of bee venom on cholecystokinin octapeptide-induced acute pancreatitis in rats. Pancreas 36: e22–e29.

    Article  CAS  PubMed  Google Scholar 

  • Shinde, A.J., K.M. Khade, A.R. Kadam, and H.M. More. 2011. Development and in vitro evaluation of chitosan gel for wound healing activity. IJARP 2: 271–274.

    CAS  Google Scholar 

  • Sibbald, R.G., and K.Y. Woo. 2008. The biology of chronic foot ulcers in persons with diabetes. Diabetes & Metabolism Research and Reviews 24: 25–30.

    Article  Google Scholar 

  • Soppirnath, K.S., and T.M. Aminabhavi. 2002. Water transport and drug release study from cross-linked polyacrylamide grafted guar gum hydrogel microspheres for the controlled release application. European Journal of Pharmaceutics and Biopharmaceutics 53: 87–98.

    Article  CAS  PubMed  Google Scholar 

  • Sung, J.H., M.R. Hwang, J.O. Kim, J.H. Lee, Y.I. Kim, J.H. Kim, S.W. Chang, S.G. Jin, J.A. Kim, W.S. Lyoo, S.S. Han, S.K. Ku, C.S. Yong, and H.G. Choi. 2010. Gel characterisation and in vivo evaluation of minocycline-loaded wound dressing with enhanced wound healing using polyvinyl alcohol and chitosan. International Journal of Pharmaceutics 15: 232–240.

    Article  Google Scholar 

  • Tandara, A.A., and T.A. Mustoe. 2004. Oxygen in wound healingmore than a nutrient. World Journal of Surgery 28: 294–300.

    Article  PubMed  Google Scholar 

  • Ueno, H., H. Yamada, I. Tanaka, N. Kaba, M. Matsuura, M. Okumura, T. Kadosawa, and T. Fujinaga. 1999. Accelerating effects of chitosan for healing at early phase of experimental open wound in dogs. Biomaterials 20: 1407–1414.

    Article  CAS  PubMed  Google Scholar 

  • Valenta, C., and B.G. Auner. 2004. The use of polymers for dermal and transdermal delivery. European Journal of Pharmaceutics and Biopharmaceutics 58: 279–289.

    Article  CAS  PubMed  Google Scholar 

  • Van Tomme, S.R., M.J. Van Steenbergen, S.C. De Smedt, C.F. Van Nostrum, and W.E. Hennink. 2005. Self-gelling hydrogels based on oppositely charged dextran microsphere. Biomaterials 26: 2129–2135.

    Article  PubMed  Google Scholar 

  • Vick, J.A., B. Mehlman, R. Brooks, S.J. Phillips, and W. Shipman. 1972. Effect of the bee venom and melittin on plasma cortisol in the unanesthetized monkey. Toxicon 10: 581–586.

    Article  CAS  PubMed  Google Scholar 

  • Vincent, A.M., J.W. Russell, P. Low, and E.L. Feldman. 2004. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocrine Reviews 25: 612–628.

    Article  CAS  PubMed  Google Scholar 

  • Wittaya-Areekul, S., C. Prahsarn, and S. Sungthongjeen. 2006. Development and in vitro evaluation of Chitosan-Eudragit RS 30D composite wound dressings. AAPS PharmSciTech. 24: E30–E36.

    Google Scholar 

  • Woessner, J.F. 1961. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Archives of Biochemistry and Biophysics 93: 440–447.

    Article  CAS  PubMed  Google Scholar 

  • Woo, K., E.A. Ayello, and R.G. Sibbald. 2007. The edge effect: current therapeutic options to advance the wound edge. Advances in Skin & Wound Care 20: 99–117.

    Article  Google Scholar 

  • Yeo, J.H., K.G. Lee, H.C. Kim, Y.L. Oh, A.J. Kim, and S.Y. Kim. 2000. The effects of Pva/chitosan/fibroin (PCF)-mixed spongy sheets on wound healing in rats. Biological and Pharmaceutical Bulletin 23: 1220–1223.

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama, F., I. Masada, K. Shimamura, T. Ikawa, and K. Monobe. 1986. Morphology and structure of highly elastic poly vinyl alcohol) hydrogel prepared by repeated freezing-and melting. Colloid and Polymer Science 264: 595–601.

    Article  CAS  Google Scholar 

  • Zhang, S., Y. Zhai, and Z. Zhang. 2011. Preparation and Properties of Polyvinyl Alcohol (PVA)/Polyvinyl Pyrrolidone (PVP) Hydrogel. Applied Mechanics and Materials 84–85: 485–489.

    Article  Google Scholar 

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  1. Department of Pharmaceutics, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt

    Mohamed A. Amin

  2. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt

    Ihab T. Abdel-Raheem

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Amin, M.A., Abdel-Raheem, I.T. Accelerated wound healing and anti-inflammatory effects of physically cross linked polyvinyl alcohol–chitosan hydrogel containing honey bee venom in diabetic rats. Arch. Pharm. Res. 37, 1016–1031 (2014). https://doi.org/10.1007/s12272-013-0308-y

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