Novel nano-insulin formulation modulates cytokine secretion and remodeling to accelerate diabetic wound healing

• Published in: Nanomedicine 2019-01, Vol.15 (1), p.47-57
• Main Authors: Kaur, Pawandeep, Sharma, Arun Kumar, Nag, Debasish, Das, Amlan, Datta, Satabdi, Ganguli, Arnab, Goel, Vanshita, Rajput, Satyendra, Chakrabarti, Gopal, Basu, Biswarup, Choudhury, Diptiman
• Format: Article
• Language: English
• Subjects: Animals; Cell Movement; Cytokines - metabolism; Diabetes; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Drug Compounding; Drug Delivery Systems; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Inflammation; Inflammation Mediators - metabolism; Insulin; Insulin - administration & dosage; Insulin - chemistry; Insulin - pharmacology; Male; Metal Nanoparticles - administration & dosage; Metal Nanoparticles - chemistry; Protein-nanoparticles interactions; Rats; Rats, Wistar; Silver - chemistry; Silver nanoparticles; Wound Healing
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2018.08.013

Little is known about insulin's wound healing capability in normal as well as diabetic conditions. We here report specific interaction of silver nanoparticles (AgNPs) with insulin by making a ~2 nm thick coat around the AgNPs and its potent wound healing efficacy. Characterization of the interaction of human insulin with silver nanoparticles showed confirmed alteration of amide-I in insulin whereas amide-II and III remained unaltered. Further, nanoparticles protein interaction kinetics showed spontaneous interaction at physiological temperature with ΔG, ΔS, Ea and Ka values −7.48, 0.076, 3.84 kcal mol−1 and 6 × 105 s−1 respectively. Insulin loaded AgNPs (IAgNPs) showed significant improvement in healing activity in vitro (HEKa cells) and in vivo (Wister Rats) in comparison with the control in both normal and diabetic conditions. The underlying mechanism was attributed to a regulation of the balance between pro (IL-6, TNFα) and anti-inflammatory cytokines (IL-10) at the wound site to promote faster wound remodeling. Graphical abstract shows the mechanism of wound healing by nano-insulin formulation (IAgNPs). IAgNPs accelerated the wound healing in diabetic conditions by inhibiting pro-inflammatory cytokines and activating anti inflammatory cytokines. [Display omitted]