title: Biodegradable nano-architectural PEGylated approach for the improved stability and anticancer efficacy of bendamustine.
abstract: Bendamustine is a drug of choice for the treatment of several cancers including non- Hodgkin lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL). The unstable nature of the drug, however, offers a major obstacle in its effective formulation development. The present study was aimed to achieve improved stability and efficacy of bendamustine via co-polymeric PEG-PLGA nanoparticulate approach. PEG-PLGA co-polymeric conjugate was synthesized and characterized by FT-IR and1H NMR spectroscopy. Bendamustine loaded nanoparticles (PLGA and PEG-PLGA) were prepared, optimized and characterized for size, zeta and electron microscopy (SEM and TEM). The average size, pdi (polydispersity index), zeta potential and entrapment efficiency for bendamustine loaded PEG-PLGA nanoparticles (PPBNP 15) was 297.3±2.055nm, 0.256±0.012, -6.62±0.081mV and 52.30±3.66%, respectively. The in vitro release studies displayed sustained release nature of bendamustine. The Krosmeyer-Peppas model was the best fit model as a result of kinetic modelling for in vitro release. The ex vivo hemolytic toxicity of the PPBNP 15 was significantly less (approx. 11%; 4 folds) compared to pure drug (p<0.05). The cytotoxicity study showed significantly higher anticancer activity against MCF-7, T47D and PC-3 cells (p<0.05) compared to naïve bendamustine. The developed biodegradable nanoparticles improved the stability of bendamustine and were equally stable, less toxic and highly effective against different cancerous cells.
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan-305817, India.
authors.forename: Iliyas
authors.initials: I
authors.lastname: Khan
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan-305817, India.
authors.forename: Avinash
authors.initials: A
authors.lastname: Gothwal
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan-305817, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Sharma
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu-180001, India.
authors.forename: Arem
authors.initials: A
authors.lastname: Qayum
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu-180001, India.
authors.forename: Shashank K
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan-305817, India. Electronic address: umeshgupta175@gmail.com.
authors.forename: Umesh
authors.initials: U
authors.lastname: Gupta
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry / Q000494:pharmacology*; D000069461:Bendamustine Hydrochloride / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D061986:MCF-7 Cells; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004337:Drug Carriers; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D000069461:Bendamustine Hydrochloride
keywords: Bendamustine; Nanoparticles; PEG-PLGA conjugate; PLGA nanoparticles