title: Curcumin loaded chitosan nanoparticles impregnated into collagen-alginate scaffolds for diabetic wound healing.
abstract: Diabetic wounds are a common complication in patients with diabetes that often lead to amputation. Although the pathophysiology of diabetic wound is multifactorial, chronic inflammation and lack of tissue regeneration leads to impair wound healing in diabetes. Application of curcumin (CUR) which is a well-known anti-inflammatory and antioxidant agent could be better strategy in diabetic wound healing. However, low bioavailability and poor stability of CUR hinders its application. Hence, in present study a novel nanohybrid scaffold has been prepared by incorporating CUR in chitosan nanoparticles (CSNPs) to improve stability and solubility followed by impregnation of prepared CUR-CSNPs into collagen scaffold (nanohybrid scaffold) for better tissue regeneration application. The prepared CUR-CSNPs were evaluated for particle size, zeta potential, SEM, differential scanning calorimetry and X-ray powder diffraction studies and the novel nanohybrid is evaluated for morphology, biodegradability, biocompatibility, in vitro drug release and in vivo wound healing studies. The results of NPs evaluation suggest the better stability and solubility of CUR. The nanohybrid scaffold showed good in vitro characteristics in terms of better water uptake, biocompatibility and sustained drug availability. The results of in vivo wound closure analysis revealed that nanohybrid scaffold treated wounds contracted significantly (p<0.001) faster than the wounds from the control and placebo scaffold groups. Further, the obtained results suggest that complete epithelialization with thick granulation tissue formation occur in nanohybrid scaffold group, whereas lack of compact collagen deposition in placebo scaffold group and presence of inflammatory cells in control group was observed. Hence, the present study suggests that the synergistic combination of CUR (anti-inflammatory and anti-oxidant), chitosan (sustain drug carrier, wound healing) and collagen (established wound healer as scaffold) is a promising strategy to address various pathological manifestations of diabetic wounds and have better wound healing capability.
authors.affiliation: Department of Pharmaceutics, JSS College of Pharmacy, JSS University, Ootacamund, Mysuru, India. Electronic address: ksnreddy87@gmail.com.
authors.forename: Veera Venkata Satyanarayana Reddy
authors.initials: VV
authors.lastname: Karri
authors.affiliation: Department of Pharmaceutics, JSS College of Pharmacy, JSS University, Ootacamund, Mysuru, India. Electronic address: gowthamsang@gmail.com.
authors.forename: Gowthamarajan
authors.initials: G
authors.lastname: Kuppusamy
authors.affiliation: Department of Pharmaceutics, JSS College of Pharmacy, JSS University, Ootacamund, Mysuru, India.
authors.forename: Siddhartha Venkata
authors.initials: SV
authors.lastname: Talluri
authors.affiliation: Department of Pharmacy, Annamalai University, Annamalai Nagar, Tamil Nadu, India.
authors.forename: Sai Sandeep
authors.initials: SS
authors.lastname: Mannemala
authors.affiliation: Department of Pharmaceutics, JSS College of Pharmacy, JSS University, Ootacamund, Mysuru, India.
authors.forename: Radhakrishna
authors.initials: R
authors.lastname: Kollipara
authors.affiliation: Department of Pharmaceutical Biotechnology, JSS College of Pharmacy, JSS University, Ootacamund, Mysuru, India.
authors.forename: Ashish Devidas
authors.initials: AD
authors.lastname: Wadhwani
authors.affiliation: Department of Pharmacology, JSS College of Pharmacy, JSS University, Ootacamund, Mysuru, India.
authors.forename: Shashank
authors.initials: S
authors.lastname: Mulukutla
authors.affiliation: Department of Pharmacology, JSS College of Pharmacy, JSS University, Ootacamund, Mysuru, India.
authors.forename: Kalidhindi Rama Satyanarayana
authors.initials: KR
authors.lastname: Raju
authors.affiliation: Pharmacokinetic Research and Development, Sun Pharmaceutical Industries Ltd., Part Survey No. 27 C.S No. 1050, Village Tandalja, Baroda, India.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Malayandi
mesh_terms: D041721:3T3-L1 Cells; D000464:Alginates / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials; D048271:Chitosan / Q000737:chemistry; D003094:Collagen / Q000737:chemistry; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D020100:Hydrogels; D008297:Male; D008422:Materials Testing; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017208:Rats, Wistar; D054457:Tissue Scaffolds / Q000737:chemistry; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000464:Alginates; D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D020100:Hydrogels; D003094:Collagen; D048271:Chitosan; D003474:Curcumin
keywords: Chitosan; Collagen; Curcumin; Diabetic wound; Nanoparticles; Scaffold