Freeze-thaw‐induced cross-linked PVA/chitosan for oxytetracycline-loaded wound dressing: the experimental design and optimization

Farzaneh Lotfipour, Mitra Alami-Milani, Sara Salatin, Aylin Hadavi, Mitra Jelvehgari

Abstract


Oxytetracycline is an antibiotic for the treatment of the infections caused by Gram-positive and Gram-negative microorganisms. Among novel formulations applied for damaged skin, hydrogels have shown to be superior as they can provide a moist environment for the wound. The purpose of this study was to prepare and evaluate the hydrogels of oxytetracycline consisted of polyvinyl alcohol (PVA) and chitosan polymers. A study design based on 4 factors and 3 levels was used for the preparation and evaluation of hydrogels formed by freeze-thaw (F-T) cycle using PVA and chitosan as a matrix-based wound dressing system. Furthermore, an experimental design was employed in order to study the effect of independent variables, namely drug amount (X1, 500-1000 mg), the amount of PVA (X2, 3.33-7.5%), the amount of chitosan                  (X3, 0.5-1%), and F-T cycle (X4, 3-7 cycles) on the dependent variables, including encapsulation efficiency, swelling index, adsorption of protein onto hydrogel surface, and skin permeation. The interaction of formulation variables had a significant effect on both physicochemical properties and permeation. Hydrogel microbial tests with sequential dilution method in Muller-Hinton broth medium were also carried out. The selected hydrogel (F6) containing 5% PVA, 0.75% chitosan, 1000 mg drug, and 3 F-T cycles was found to have increased encapsulation efficiency, gel strength, and higher skin permeation suitable for faster healing of wounds. Results showed the biological stability of oxytetracycline HCl in the hydrogel formulation with a lower dilution of the pure drug. Thus, oxytetracycline-loaded hydrogel could be a potential candidate to be used as a wound dressing system.


Keywords


Chitosan; Hydrogel; Oxytetracycline; Polyvinyl alcohol; Skin.

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References


Park H, Park K, Shalaby WSW. Biodegradable Hydrogels for Drug Delivery. CRC Press; 1993. pp. 59-84.

Fernandez JG, Ingber DE. Bioinspired chitinous material solutions for environmental sustainability and medicine. Adv Func Mat. 2013;23(36):4454-4466.

Tokarev I, Minko S. Stimuli Jorgensen JH, Turnidge JD. Susceptibility test methods: dilution and disk diffusion methods. Manual Clin Microbiol, Eleventh Edition: American Society of Microbiology; 2015. p. 1253-73.responsive porous hydrogels at interfaces for molecular filtration, separation, controlled release, and gating in capsules and membranes. Adv Mater. 2010;22(31):3446-3462.

Welzel PB, Grimmer M, Renneberg C, Naujox L, Zschoche S, Freudenberg U, et al. Macroporous starPEG-heparin cryogels. Biomacromolecules. 2012;13(8):2349-2358.

Hoare TR, Kohane DS. Hydrogels in drug delivery: progress and challenges. Polymer. 2008;49(8): 1993-2007.

Bhattarai N, Gunn J, Zhang M. Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Deliv Rev. 2010;62(1):83-99.

Anumolu SS, Menjoge AR, Deshmukh M, Gerecke D, Stein S, Laskin J, et al. Doxycycline hydrogels with reversible disulfide crosslinks for dermal wound healing of mustard injuries. Biomaterials. 2011;32(4):1204-1217.

Boateng JS, Matthews KH, Stevens HN, Eccleston GM. Wound healing dressings and drug delivery systems: a review. J Pharm Sci. 2008;97(8):2892-2923.

Leaper DJ. Silver dressings: their role in wound management. Int Wound J. 2006;3(4):282-294.

Hassan CM, Peppas NA. Structure, and morphology of freeze/thawed PVA hydrogels. Macromolecules. 2000;33(7):2472-2479.

Wan W, Bannerman AD, Yang L, Mak H. Poly (Vinyl Alcohol) Cryogels for Biomedical Applications. Springer; 2014. pp. 283-321.

Ricciardi R, D'Errico G, Auriemma F, Ducouret G, Tedeschi AM, De Rosa C, et al. Short-time dynamics of solvent molecules and supramolecular organization of poly (vinyl alcohol) hydrogels obtained by freeze/thaw techniques. Macromolecules. 2005;38(15):6629-6639.

Amin MA, Abdel-Raheem IT. 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. 2014;37(8):1016-1031.

Kathuria N, Tripathi A, Kar KK, Kumar A. Synthesis and characterization of elastic and macroporous chitosan–gelatin cryogels for tissue engineering. Acta Biomater. 2009;5(1):406-418.

Petković H, Cullum J, Hranueli D, Hunter IS, Perić-Concha N, Pigac J, et al. Genetics of Streptomyces rimosus, the oxytetracycline producer. Microbiol Mol Biol Rev. 2006;70(3):704-728.

Delf Loveymi B, Jelvehgari M, Zakeri-Milani P, Valizadeh H. Statistical optimization of oral vancomycin-eudragit rs nanoparticles using response surface methodology. Iran J Pharm Res. 2012;11(4):1001-1012.

Părpăriţă E, Cheaburu CN, Pațachia SF, Vasile C. Polyvinyl alcohol/chitosan/montmorillonite nanocomposites preparation by freeze/thaw cycles and characterization. Acta Chemica Iasi. 2014;22(2):75-96.

Tabatabaei Yazdi F, Alizadeh Behbahani B, Mortazavi A. Investigating the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the Lavandula stoechas L. and Rosmarinus officinalis L. extracts on pathogen bacterias “in vitro”. J Paramed Sci. 2014;5(2):91-101.

Jorgensen JH, Turnidge JD. Susceptibility test methods: dilution and disk diffusion methods. Manual Clin Microbiol, Eleventh Edition: American Society of Microbiology; 2015. pp. 1253-73.

Hemmila MR, BAKER JJ, Dolgachev VA, Ciotti SM, Wang S. Topical nanoemulsion therapy for wounds. Google Patents; 2015.

Pendekal MS, Tegginamat PK. Formulation and evaluation of a bioadhesive patch for buccal delivery of tizanidine. Acta Pharm Sin B. 2012;2(3):318-324.

Doulabi AH, Mirzadeh H, Imani M, Samadi N. Chitosan/polyethylene glycol fumarate blend film: physical and antibacterial properties. Carbohydr Polym. 2013;92(1):48-56.

Mehdinavaz Aghdam R, Shakhesi S, Najarian S, Malek Mohammadi M, Ahmadi Tafti SH, Mirzadeh H. Fabrication of a nanofibrous scaffold for the in vitro culture of cardiac progenitor cells for myocardial regeneration. Int J Polym Mater Polym Biomaterials. 2014;63(5):229-239.

Sharma N, Jain S, Sardana S. Muccoadhesive drug delivery system: A Review. J Adv Pharm Edu Res. 2013;3(1):9-12.

Sintov AC, Botner S. Transdermal drug delivery using microemulsion and aqueous systems: influence of skin storage conditions on the in vitro permeability of diclofenac from aqueous vehicle systems. Int J Pharm. 2006;311(1-2):55-62.

Sung JH, Hwang MR, Kim JO, Lee JH, Kim YI, Kim JH, et al. Gel characterization and in vivo evaluation of minocycline-loaded wound dressing with enhanced wound healing using polyvinyl alcohol and chitosan. Int J Pharm. 2010;392(1-2):232-240.

Chen MC, Ling MH, Lai KY, Pramudityo E. Chitosan microneedle patches for sustained transdermal delivery of macromolecules. Biomacromolecules. 2012;13(12):4022-4031.

Sakai T, Matsunaga T, Yamamoto Y, Ito C, Yoshida R, Suzuki S, et al. Design and fabrication of a high-strength hydrogel with ideally homogeneous network structure from tetrahedron-like macromonomers. Macromolecules. 2008;41(14):5379-5384.

Van Kampen E. Controlling Protein Permeability in Hydrogels for Drug Delivery Applications. USA: University of Kansas; 2016. A dissertation.

Chapman RG, Ostuni E, Liang MN, Meluleni G, Kim E, Yan L, et al. Polymeric thin films that resist the adsorption of proteins and the adhesion of bacteria. Langmuir. 2001;17(4):1225-1233.

Tran NQ, Joung YK, Lih E, Park KD. In situ forming and rutin-releasing chitosan hydrogels as injectable dressings for dermal wound healing. Biomacromolecules. 2011;12(8):2872-2880.

Yaa A. Development of a chitosan-based glucose responsive nanoparticulate insulin delivery system: University of Nottingham; 2014.

Kong M, Chen XG, Xing K, Park HJ. Antimicrobial properties of chitosan and mode of action: a state of the art review. Int J Food Microbiol. 2010;144(1):51-63.

Salatin S, Barar J, Barzegar-Jalali M, Adibkia Kh, Kiafar F, Jelvehgari M. Development of a nanoprecipitation method for the entrapment of a very water soluble drug into Eudragit RL nanoparticles. Res Pharm Sci. 2017;12(1):1-14.

Hasanpouri A, Lotfipour F, Ghanbarzadeh S, Hamishehkar H. Improvement of dermal delivery of tetracycline using vesicular Nanostructures. Res Pharm Sci. 2018;13(5):385-393.


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