Utilization of Gelling Polymer to Formulate Nanoparticles Loaded with Epalrestat-Cyclodextrin Inclusion Complex: Formulation, Characterization, In-Silico Modelling and In-Vivo Toxicity Evaluation

Polymers

Imran Nazir¹  Amal M. Sindi²  Khaled M. Hosny³  Zunaira Alvi⁴  Muhammad Akhtar⁴  Hadia Sadaquat⁴  Nisar U. Rahman⁵  Barkat A. Khan⁶ 

[1] Bahawal Victoria Hospital, Bahawalpur 63100, Punjab, Pakistan;Department of Oral Diagnostic Sciences, Faculty of Dentistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia;Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia;Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Punjab, Pakistan;Department of Pharmacy, Royal Institute of Medical Sciences (RIMS), Multan 60000, Punjab, Pakistan;Drug Design and Cosmetics Lab (DDCL), Gomal Center of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Khyber Pakhtoonkhwa, Pakistan;

关键词: epalrestat;    inclusion complex;    solubility;    chitosan nanoparticles;    in-silico modeling;    in-vivo toxicity evaluation;   

DOI  :  10.3390/polym13244350

来源: DOAJ

【 摘 要 】

Epalrestat (EPL) is an aldose reductase inhibitor with poor aqueous solubility that affects its therapeutic efficacy. The research study was designed to prepare epalrestat-cyclodextrins (EPL-CDs) inclusion complexes to enhance the aqueous solubility by using beta-cyclodextrin (β-CD) and sulfobutyl ether₇ β-CD (SBE₇ β-CD). Furthermore, polymeric nanoparticles (PNPs) of EPL-CDs were developed using chitosan (CS) and sodium tripolyphosphate (sTPP). The EPL-CDs complexed formulations were then loaded into chitosan nanoparticles (CS NPs) and further characterized for different physico-chemical properties, thermal stability, drug-excipient compatibility and acute oral toxicity studies. In-silico molecular docking of cross-linker with SBE₇ β-CD was also carried out to determine the binding site of the CDs with the cross-linker. The sizes of the prepared NPs were laid in the range of 241.5–348.4 nm, with polydispersity index (PDI) ranging from 0.302–0.578. The surface morphology of the NPs was found to be non-porous, smooth, and spherical. The cumulative percentage of drug release from EPL-CDs loaded CS NPs was found to be higher (75–88%) than that of the pure drug (25%). Acute oral toxicity on animal models showed a biochemical, histological profile with no harmful impact at the cellular level. It is concluded that epalrestat-cyclodextrin chitosan nanoparticles (EPL-CDs-CS NPs) with improved solubility are safe for oral administration since no toxicity was reported on vital organs in rabbits.

【 授权许可】

Unknown