title: PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery.
abstract: Current approaches to encapsulate and deliver therapeutic compounds have focused on developing liposomal and biodegradable polymeric nanoparticles (NPs), resulting in clinically approved therapeutics such as Doxil/Caelyx and Genexol-PM, respectively. Our group recently reported the development of biodegradable core-shell NP systems that combined the beneficial properties of liposomal and polymeric NPs for controlled drug delivery. Herein we report the parameters that alter the biological and physicochemical characteristics, stability, drug release properties and cytotoxicity of these core-shell NPs. We further define scalable processes for the formulation of these NPs in a reproducible manner. These core-shell NPs consist of (i) a poly(D,L-lactide-co-glycolide) hydrophobic core, (ii) a soybean lecithin monolayer, and (iii) a poly(ethylene glycol) shell, and were synthesized by a modified nanoprecipitation method combined with self-assembly. Preparation of the NPs showed that various formulation parameters such as the lipid/polymer mass ratio and lipid/lipid-PEG molar ratio controlled NP physical stability and size. We encapsulated a model chemotherapy drug, docetaxel, in the NPs and showed that the amount of lipid coverage affected its drug release kinetics. Next, we demonstrated a potentially scalable process for the formulation, purification, and storage of NPs. Finally, we tested the cytotoxicity using MTT assays on two model human cell lines, HeLa and HepG2, and demonstrated the biocompatibility of these particles in vitro. Our data suggest that the PLGA-lecithin-PEG core-shell NPs may be a useful new controlled release drug delivery system.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Juliana M
authors.initials: JM
authors.lastname: Chan
authors.forename: Liangfang
authors.initials: L
authors.lastname: Zhang
authors.forename: Kai P
authors.initials: KP
authors.lastname: Yuet
authors.forename: Grace
authors.initials: G
authors.lastname: Liao
authors.forename: June-Wha
authors.initials: JW
authors.lastname: Rhee
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Omid C
authors.initials: OC
authors.lastname: Farokhzad
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000494:pharmacology; D000077143:Docetaxel; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054709:Lecithins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D043823:Taxoids / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; D054709:Lecithins; D008055:Lipids; D043823:Taxoids; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols