FORMULATION, CHARACTERIZATION AND OPTIMIZATION OF PLGA-CHITOSAN-LOADED FATTY ACID SCAFFOLDS FOR THE TREATMENT OF DIABETIC WOUNDS
DOI:
https://doi.org/10.22159/ijap.2024v16i6.51509Keywords:
PUFAs, Chitosan, Scaffolds, PLGA, Diabetes, Wounds, In vitro drug release, In vitro studiesAbstract
Objective: The objective of the current research to formulate Eicosapentanoic Acid/Decosahexanoic Acid (EPA/DHA)incorporated into Chitosan (CS)and Poly-Lactic-Glycolic Acid (PLGA), nanoparticles composite scaffolds to the accelerated diabetic wound healing. The main focus of this present research is to evaluate and develop the chitosan–PLGA biodegradable polymer scaffolds loaded with long-chain omega-3 Polyunsaturated Fatty Acids (PUFA’s) (EPA/DHA).
Methods: Nano scaffolds were prepared by solvent evaporation method loaded with CS-PLGA, EPA and DHA to treat diabetic wounds at targeted site as pharmacotherapeutically. Upon investigation, the developed biodegradable crosslinked scaffold possesses matrix degradation, optimal porosity, prolonged drug release action than the non-cross linked scaffold. The prepared formulation containing CS-PLGA loaded with EPA/DHA were formulated as nanoscaffold for wound topical applications was carried out by using freeze drying process.
Results: The prepared CS-PLGA nano scaffolds were optimized and evaluated for physicochemical properties, dynamic light scattering with a particle size of 248 nm and zeta of-24mVand Scanning Electron Microscopy (SEM) were found to be spherical. In addition, the optical properties of EPA/DHA and PLGA, along with CS, can be compared by examining their absorption and wavelength (nm) using UV-visible spectroscopy. The structural and functional groups of the prepared end products were characterized by Fourier-Transformed Infrared Spectroscopy (FT-IR) has shown good compatibility with excipients and nanoformulaton, in vitro drug release studies done by using dialysis bag membrane results find that first-order Higuchi model was followed showing 20% release in first 0.2 h. MTT(3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide) assay was carried out and it showed that both crosslinked and non-crosslinked scaffolds(110 and 120%) improved cell growth when compared to control (100%).
Conclusion: Finally, the results showed that the PLGA, CS nanoscaffolds containing 98% of PUFA’s (EPA/DHA) have increased in proinflammatory cytokines production at the particular wound site and thus accelerated healing activity, depending on the pre-clinical studies have trespassed, the therapeutic potential to penetrating at wound site. The optimized nanoformulation could be a better formulation for targeting and treatment of diabetic wounds at an optimal ratio.
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Williams R, Karuranga S, Malanda B, Saeedi P, Basit A, Besancon S. Global and regional estimates and projections of diabetes-related health expenditure: results from the international diabetes federation diabetes atlas 9th edition. Diabetes Res Clin Pract. 9th Ed. 2020 Apr 1;162:108072. doi: 10.1016/j.diabres.2020.108072, PMID 32061820.
Siersma V, Thorsen H, Holstein PE, Kars M, Apelqvist J, Jude EB. Health-related quality of life predicts major amputation and death but not healing in people with diabetes presenting with foot ulcers: the eurodiale study. Diabetes Care. 2014;37(3):694-700. doi: 10.2337/dc13-1212, PMID 24170755.
Morimoto M, Lee EY, Zhang X, Inaba Y, Inoue H, Ogawa M. Eicosapentaenoic acid ameliorates hyperglycemia in high-fat diet sensitive diabetes mice in conjunction with restoration of hypoadiponectinemia. Nutr Diabetes. 2016;6(6):e213. doi: 10.1038/nutd.2016.21, PMID 27348201.
Qin L, Mei Y, An C, Ning R, Zhang H. Docosahexaenoic acid administration improves diabetes-induced cardiac fibrosis through enhancing fatty acid oxidation in cardiac fibroblast. J Nutr Biochem. 2023;113:109244. doi: 10.1016/j.jnutbio.2022.109244, PMID 36470335.
Panda BP, Krishnamoorthy R, Bhattamisra SK, Shivashekaregowda NK, Seng LB, Patnaik S. Fabrication of second generation smarter PLGA based nanocrystal carriers for improvement of drug delivery and therapeutic efficacy of gliclazide in type-2 diabetes rat model. Sci Rep. 2019;9(1):17331. doi: 10.1038/s41598-019-53996-4, PMID 31758056.
Panda BP, Krishnamoorthy R, Shivashekaregowda NK, Patnaik S. Influence of poloxamer 188 on design and development of second-generation PLGA nanocrystals of metformin hydrochloride. Nano Biomed Eng. 2018;10(4):334-43. doi: 10.5101/nbe.v10i4.p334-343.
Sanapalli BK, Yele V, Singh MK, Thumbooru SN, Parvathaneni M, Karri VV. Human beta defensin-2 loaded PLGA nanoparticles impregnated in collagen chitosan composite scaffold for the management of diabetic wounds. Biomed Pharmacother. 2023;161:114540. doi: 10.1016/j.biopha.2023.114540, PMID 36934557.
Ahmed SS, Baqi MA, Baba MZ, Jawahar N. Formulation characterization and optimization of folic acid tailored daidzein solid lipid nanoparticles for the improved cytotoxicity against colon cancer cells. Int J App Pharm. 2024 Mar;16(2):320-8. doi: 10.22159/ijap.2024v16i2.49879.
Natarajan J, Sanapalli BK, Bano M, Singh SK, Gulati M, Karri VV. Nanostructured lipid carriers of pioglitazone loaded collagen/chitosan composite scaffold for diabetic wound healing. Adv Wound Care. 2019 Oct 1;8(10):499-513. doi: 10.1089/wound.2018.0831, PMID 31737408.
Mat Saad AZ, Khoo TL, Halim AS. Wound bed preparation for chronic diabetic foot ulcers. ISRN Endocrinol. 2013;2013(1):608313. doi: 10.1155/2013/608313, PMID 23476800.
Ahmed SS, Sriramcharan P, Arivuselam R, Raman R, Venkatachalam S, Natarajan J. Green synthesis of bovine serum albumin tailored silver nanoparticles from aspergillus fumigatus: statistical optimization characterization antioxidant and cytotoxicity evaluation on colon cancer cells. Applied Organom Chemis. 2024 Apr;38(4):e7386. doi: 10.1002/aoc.7386.
Hu X, He J, Qiao L, Wang C, Wang Y, Yu R. Multifunctional dual network hydrogel loaded with novel tea polyphenol magnesium nanoparticles accelerates wound repair of MRSA infected diabetes. Adv Funct Materials. 2024 Feb 6;34(22):2312140. doi: 10.1002/adfm.202312140.
Sharma A, Mehta V, Parashar A, Patrwal R, Malairaman U. Solid lipid nanoparticle: fabricated through nanoprecipitation and their physicochemical characterization. Int J Pharm Pharm Sci. 2016 Aug 12;8(10):144. doi: 10.22159/ijpps.2016v8i10.13207.
Varma R, Vasudevan S. Extraction characterization and antimicrobial activity of chitosan from horse mussel modiolus Modiolus. ACS Omega. 2020 Aug 18;5(32):20224-30. doi: 10.1021/acsomega.0c01903, PMID 32832775.
Mahalingam M, Krishnamoorthy K. Camptothecin loaded poly (meth acyclic acid-co-methyl-methyacrylate) nanoparticles: fabrication characterization and cytotoxicity studies. Int J Pharm Pharm Sci. 2015;7(10):135-40.
Chen Y, Zhao W, Dai H. Porous PLGA-PEG nerve conduit decorated with oriented electrospun chitosan RGD nanofibre. J Mater Res Technol. 2021 Nov 1;15:86-98. doi: 10.1016/j.jmrt.2021.07.117.
Montanheiro TL, Montagna LS, Patrulea V, Jordan O, Borchard G, Ribas RG. Enhanced water uptake of PHBV scaffolds with functionalized cellulose nanocrystals. Polym Test. 2019;79:106079. doi: 10.1016/j.polymertesting.2019.106079.
Rajput IB, Tareen FK, Khan AU, Ahmed N, Khan MF, Shah KU. Fabrication and in vitro evaluation of chitosan gelatin-based aceclofenac loaded scaffold. Int J Biol Macromol. 2023 Jan 1;224:223-32. doi: 10.1016/j.ijbiomac.2022.10.118, PMID 36265543.
Intini C, Elviri L, Cabral J, Mros S, Bergonzi C, Bianchera A. 3D-printed chitosan-based scaffolds: an in vitro study of human skin cell growth and an in vivo wound healing evaluation in experimental diabetes in rats. Carbohydr Polym. 2018 Nov 1;199:593-602. doi: 10.1016/j.carbpol.2018.07.057, PMID 30143167.
Jahangir MA, Khan R, Sarim Imam S. Formulation of sitagliptin loaded oral polymeric nano scaffold: process parameters evaluation and enhanced antidiabetic performance. Artif Cells Nanomed Biotechnol. 2018 Oct 31;46 Suppl 1:66-78. doi: 10.1080/21691401.2017.1411933, PMID 29226729.
Khazaeli P, Alaei M, Khaksarihadad M, Ranjbar M. Preparation of PLA/chitosan nanoscaffolds containing cod liver oil and experimental diabetic wound healing in male rats study. J Nanobiotechnology. 2020 Dec;18(1):176. doi: 10.1186/s12951-020-00737-9, PMID 33256764.
Bhardwaj A, Modi KP. Antidiabetic and antihyperlipidaemic activity of nelumbo nucifera gaertn ethanol seed extract in streptozotocin-induced diabetic rats. Int J Pharm Pharm Sci. 2017;9(10):197. doi: 10.22159/ijpps.2017v9i10.21455.
Anitha R, Vaikkath D, Shenoy SJ, Nair PD. Tissue-engineered islet like cell clusters generated from adipose tissue-derived stem cells on three-dimensional electrospun scaffolds can reverse diabetes in an experimental rat model and the role of porosity of scaffolds on cluster differentiation. J Biomed Mater Res A. 2020 Mar;108(3):749-59. doi: 10.1002/jbm.a.36854, PMID 31788956.
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Copyright (c) 2024 SHILPA.N. THUMBOORU, SYED SUHAIB AHMED, BALAJI HARI, GOWRAV MP, KARRI VVS NARAYANA REDDY
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