title: Synthesis and in vitro evaluation of a pH-sensitive PLA-PEG-folate based polymeric micelle for controlled delivery of docetaxel.
abstract: pH-responsive docetaxel-conjugated poly (lactic acid) (PLA)-polyethyleneglycol (PEG) micellar formulation was synthesized via acid labile hydrazone linkage. Levulinic acid (LEV) was used as a linker between docetaxel (DTX) and hydrazine. Targeted delivery of DTX was achieved by conjugation of folate to PEG segment. The DTX conjugated polymeric micelles were about 181 nm in diameter and their critical micelle concentration was 5.18 μg/ml. DTX was released from micelles in a pH-dependent manner. The results showed a significant difference in DTX release from polymeric micelles at pH 5.0 and pH 7.4. Cytotoxicity assays using methyl tetrazolium (MTT), neutral red (NR) and lactate dehydrogenase (LDH) demonstrated a decreased cytotoxic activity of the drug containing nanoconjugate compared with free DTX that appears to be contributed to the sustained release of drug from micelles. Based on these results, it is expected that this pH-responsive nanoconjugate is promising as a useful carrier for targeted delivery of anticancer agents.
authors: Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Zahra
authors: Z
authors: Hami
authors: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mohsen
authors: M
authors: Amini
authors: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mahmoud
authors: M
authors: Ghazi-Khansari
authors: Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology & Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.
authors: Seyed Mehdi
authors: SM
authors: Rezayat
authors: Aerosol Research Laboratory, Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: gilani@tums.ac.ir.
authors: Kambiz
authors: K
authors: Gilani
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry*; D008823:Micelles; D015394:Molecular Structure; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D005492:Folic Acid
keywords: Docetaxel; PLA–PEG di-block copolymer; Targeted drug delivery; pH-sensitive polymeric micelles