PMID- 31524015 OWN - NLM STAT- MEDLINE DCOM- 20200131 LR - 20211204 IS - 1521-0464 (Electronic) IS - 1071-7544 (Print) IS - 1071-7544 (Linking) VI - 26 IP - 1 DP - 2019 Dec TI - Design and optimization of crocetin loaded PLGA nanoparticles against diabetic nephropathy via suppression of inflammatory biomarkers: a formulation approach to preclinical study. PG - 849-859 LID - 10.1080/10717544.2019.1642417 [doi] AB - Diabetic nephropathy (DN) is a serious complication of diabetes mellitus whose expand process is linked with the fibrosis, renal hypertrophy and inflammation. The current study was to formulate and optimize the nano-formulation of crocetin (CT-PLGA-NPs) against Streptozotocin-induced renal nephropathy in rats. Double emulsion evaporation technique was used for the preparation of CT-PLGA-NPs. CT-PLGA-NPs were scrutinized for polydispersity index, size, gastric stability, entrapment, drug-loading capacity and in-vitro drug release and in vivo preclinical study. Single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg) and rats were divided into different group. Renal function and metabolic parameters of urine and serum were estimated. Fibrotic protein, renal pro-inflammatory cytokines and degree of renal damage expression were also determined. We also estimated the fibronectin, type IV collagen and transforming growth factor-beta1 for a possible mechanism of action. Crocetin supplement (10 mg/kg) and CT-PLGA-NPs exhibited the accumulation of the drug in kidney and liver of diabetic rats. Crocetin reduced the BGL and enhanced plasma insulin and body weight. Dose dependent treatment of crocetin significantly (p < .001) down-regulated the expression of renal tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin (IL)-1beta (IL-1beta) and Monocyte Chemoattractant Protein-1 (MCP-1). Crocetin significantly (p < .001) altered the expression of fibronectin, type IV collagen, and transforming growth factor-beta1 (TGF-1beta). Crocetin significantly (p < .001) down-regulated the protein kinase C activity and the expression of nuclear factor kappaB (NF-kappaB) p65 activity and protein production in renal tissue. On the basis of the available result, we can conclude that nano-formulation of crocetin could attenuate the diabetic nephropathy via antifibrotic and anti-inflammatory effect. FAU - Yang, Xiaodong AU - Yang X AD - Department of General Medicine, Zhumadian Central Hospital , Zhumadian , China. LA - eng PT - Journal Article PL - England TA - Drug Deliv JT - Drug delivery JID - 9417471 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (trans-sodium crocetinate) RN - 11103-57-4 (Vitamin A) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 36-88-4 (Carotenoids) RN - 5W494URQ81 (Streptozocin) SB - IM MH - Animals MH - Anti-Inflammatory Agents/chemistry/pharmacology MH - Biomarkers/*metabolism MH - Carotenoids/*administration & dosage/*chemistry MH - Cytokines/metabolism MH - Diabetes Mellitus, Experimental/chemically induced/drug therapy/metabolism MH - Diabetic Nephropathies/*drug therapy/metabolism MH - Down-Regulation/drug effects MH - Drug Evaluation, Preclinical MH - Inflammation/*drug therapy/metabolism MH - Inflammation Mediators/metabolism MH - Kidney/drug effects/metabolism MH - Nanoparticles/*chemistry MH - Polylactic Acid-Polyglycolic Acid Copolymer/*chemistry MH - Rats MH - Rats, Wistar MH - Signal Transduction/drug effects MH - Streptozocin/pharmacology MH - Vitamin A/analogs & derivatives PMC - PMC6761602 OTO - NOTNLM OT - Crocetin OT - NF-kB OT - PLGA loaded nanoparticles OT - antidiabetic OT - antifibrotic OT - protein kinase C OT - streptozotocin EDAT- 2019/09/17 06:00 MHDA- 2020/02/01 06:00 PMCR- 2019/09/14 CRDT- 2019/09/17 06:00 PHST- 2019/09/17 06:00 [entrez] PHST- 2019/09/17 06:00 [pubmed] PHST- 2020/02/01 06:00 [medline] PHST- 2019/09/14 00:00 [pmc-release] AID - 1642417 [pii] AID - 10.1080/10717544.2019.1642417 [doi] PST - ppublish SO - Drug Deliv. 2019 Dec;26(1):849-859. doi: 10.1080/10717544.2019.1642417.