title: Enhanced apoptotic and anticancer potential of paclitaxel loaded biodegradable nanoparticles based on chitosan.
abstract: Taxanes have established and proven effectivity against different types of cancers; in particular breast cancers. However, the high hemolytic toxicity and hydrophobic nature of paclitaxel and docetaxel have always posed challenges to achieve safe and effective delivery. Use of bio-degradable materials with an added advantage of nanotechnology could possibly improve the condition so as to achieve better and safe delivery. In the present study paclitaxel loaded chitosan nanoparticles were formulated and optimized using simple w/o nanoemulsion technique. The observed average size, pdi, zeta potential, entrapment efficiency and drug loading for the optimized paclitaxel loaded chitosan nanoparticle formulation (PTX-CS-NP-10) was 226.7±0.70nm, 0.345±0.039, 37.4±0.77mV, 79.24±2.95% and 11.57±0.81%; respectively. Nanoparticles were characterized further for size by Transmission Electron Microscopy (TEM). In vitro release studies exhibited sustained release pattern and more than 60% release was observed within 24h. Enhanced in vitro anticancer activity was observed as a result of MTT assay against triple negative MDA-MB-231 breast cancer cell lines. The observed IC50values obtained for PTX-CS-NP-10 was 9.36±1.13μM and was almost 1.6 folds (p<0.05) less than the pure drug. Similarly, PTX-CS-NP-10 were extremely biocompatible and safe as observed for haemolytic toxicity which was almost 4 folds less (p<0.05) than the naïve drug. Anticancer activity was further evaluated using flow cytometry for apoptosis. Cell apoptosis study revealed that PTX-CS-NP-10 treatment resulted into enhanced (almost double) late cell apoptosis than naïve paclitaxel. Hence the developed nanoparticulate formulation not only reduced the overall toxicity but also resulted into improved anticancer efficacy of paclitaxel. It can be concluded that a robust, stable and comparatively safe nanoformulation of paclitaxel was developed, characterized and evaluated.
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Ajmer, Rajasthan, 305817, India. Electronic address: umeshgupta175@gmail.com.
authors.forename: Umesh
authors.initials: U
authors.lastname: Gupta
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Ajmer, Rajasthan, 305817, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, 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, Bandar Sindri, 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, Bandar Sindri, Ajmer, Rajasthan, 305817, India.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Sharma
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP, 226031 India.
authors.forename: Yuvraj
authors.initials: Y
authors.lastname: Singh
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP, 226031 India.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Chourasia
authors.affiliation: Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Ajmer, Rajasthan, 305817, India.
authors.forename: Vipin
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D011092:Polyethylene Glycols; D048271:Chitosan; D017239:Paclitaxel
keywords: Biodegradable polymers; Chitosan; Nano-emulsion; Nanoparticles; Paclitaxel