Tailoring the properties of mPEG-PLLA nanoparticles for better encapsulation and tuned release of the hydrophilic anticancer drug.
Gemcitabine is used as a first-line drug for treating many solid tumours. However, it suffers from a major drawback of strong side effects and short plasma half-life because of degradation by enzyme when administered intravenously. Polyesters and copolyesters are the most widely used and preferred class of biodegradable polymer. In the present work, efforts have been made to prepare poly(ethylene glycol) monomethoxy ether-poly(L-lactide) (mPEG-PLLA), a biodegradable amphiphilic copolymer with a view to improve the entrapment and tuned release of hydrophilic drug gemcitabine. The different mPEG-PLLA copolymers were synthesized with the varying ratios of mPEG and characterized by different techniques namely FTIR and1H NMR spectroscopy, solution viscosity, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC). Gemcitabine-loaded nanoparticles were prepared using mPEG-PLLA copolymers by two methods i.e. nanoprecipitation and double emulsion solvent evaporation. The nanoprecipitation method showed very less entrapment and polymer solubility in the acetone-water mixture leading to uncontrolled polymer precipitation. The difficulties encountered in the nanoprecipitation method were overcome with the help of the double emulsion (w/o/w) solvent evaporation technique. It has been observed from the results that biodegradable copolymer nanoparticles protect the drug from degradation and also help in controlling the release of encapsulated drug. The properties of nanoparticles can be tailored by varying the composition of mPEG in order to get improved entrapment efficiency and desired drug release. The nanoparticles were assessed for their in vitro cytotoxicity (MTT and FACS) and cellular uptake (fluorescence microscopy) study which showed very promising results. Nanoparticles were also studied for their in vivo release after intravenous administration to Wistar albino rats, which successfully showed controlled drug release for more than 14 days.
Polymer Science and Engineering Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411 008, India.
Sachin S
SS
Surwase
Department of Pharmaceutics, STES, SKN College of Pharmacy, Kondhwa, Pune, 411 038, India.
Neha M
NM
Munot
Polymer Science and Engineering Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411 008, India.
Bhaskar B
BB
Idage
Polymer Science and Engineering Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411 008, India. sb.idage@ncl.res.in.
Susheela B
SB
Idage
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D061986:MCF-7 Cells; D008297:Male; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D017208:Rats, Wistar; D012235:Rhodamines / Q000008:administration & dosage / Q000737:chemistry; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D005456:Fluorescent Dyes; D011091:Polyesters; D012235:Rhodamines; C492425:methoxy poly(ethylene glycol)-poly(lactide); D003841:Deoxycytidine; D011092:Polyethylene Glycols; C029773:rhodamine B; D000093542:Gemcitabine
Biodegradable polymer; Controlled release; Double emulsion; Gemcitabine; Nanoprecipitation; Tuned degradation