title: Surface-coated PLA nanoparticles loaded with temozolomide for improved brain deposition and potential treatment of gliomas: development, characterization and in vivo studies.
abstract: Hydrophobicity of PLA nanoparticles makes them a good substrate for macrophageal and reticulo-endothelial system uptake. Long-circulating properties can be imparted to these particles by coating them with hydrophilic stabilizers. Surface-modified PLA nanoparticles loaded with anti-cancer agent temozolomide were fabricated by solvent evaporation method and coated with surface modifiers. Selection of the surface modifier was based upon uptake of nanoparticles by K9 cells (liver cells). The particles were prepared and characterized for various physicochemical properties using transmission electron microscopy, differential scanning calorimetry, powder X-ray diffraction and in vitro dissolution studies. In vitro BBB permeation studies were performed using the co-culture model developed by using Madin-Darby canine kidney and C6 glioma cells as endothelial and glial cells, respectively. In vitro C6 glioma cell cytotoxicity, cellular proliferation, cellular migration and cellular uptake studies due to developed nanoparticles was assessed. In vivo studies such as pharmacokinetics, qualitative and quantitative biodistribution studies were performed for the developed nanoparticles. Drug-loaded nanoparticles with entrapment efficiency of 50% were developed. PEG-1000 and polysorbate-80 coated nanoparticles were least taken up by the liver cells. Characterization of the nanoparticles revealed formation of spherical shape nanoparticles, with no drug and excipient interaction. In vivo pharmacokinetics of developed nanoparticles depicted enhancement of half-life, area under the curve and mean residence time of the drug. Qualitative and quantitative biodistribution studies confirmed enhanced permeation of the drug into the brain upon loading into nanoparticles with less deposition in the highly perfused organs like lung, liver, spleen, heart and kidney.
authors.affiliation: a Department of Pharmaceutics , CU Shah College of Pharmacy , Mumbai , Maharashtra , India .
authors.forename: Darshana
authors.initials: D
authors.lastname: Jain
authors.affiliation: b SVKM's Dr. Bhanuben Nanavati College of Pharmacy , Mumbai , Maharashtra , India .
authors.forename: Amrita
authors.initials: A
authors.lastname: Bajaj
authors.affiliation: a Department of Pharmaceutics , CU Shah College of Pharmacy , Mumbai , Maharashtra , India .
authors.forename: Rajani
authors.initials: R
authors.lastname: Athawale
authors.affiliation: a Department of Pharmaceutics , CU Shah College of Pharmacy , Mumbai , Maharashtra , India .
authors.forename: Shruti
authors.initials: S
authors.lastname: Shrikhande
authors.affiliation: c ACTREC, Tata Memorial Cancer Centre , Mumbai , Maharashtra , India , and.
authors.forename: Peeyush N
authors.initials: PN
authors.lastname: Goel
authors.affiliation: c ACTREC, Tata Memorial Cancer Centre , Mumbai , Maharashtra , India , and.
authors.forename: Yuvraj
authors.initials: Y
authors.lastname: Nikam
authors.affiliation: c ACTREC, Tata Memorial Cancer Centre , Mumbai , Maharashtra , India , and.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Gude
authors.affiliation: d Cipla Pvt. Ltd , Mumbai , Maharashtra , India.
authors.forename: Satish
authors.initials: S
authors.lastname: Patil
authors.affiliation: d Cipla Pvt. Ltd , Mumbai , Maharashtra , India.
authors.forename: Preeti
authors.initials: P
authors.lastname: Prashant Raut
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005910:Glioma / Q000188:drug therapy*; D006207:Half-Life; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011136:Polysorbates / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D000077204:Temozolomide; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D011136:Polysorbates; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D003606:Dacarbazine; D000077204:Temozolomide
keywords: Brain tumor; PEG-1000; PLA; polymeric nanoparticles; temozolomide