title: Formulation and dosage of therapeutic nanosuspension for active targeting of docetaxel (WO 2014210485A1).
abstract: Non-specificity and drug resistance are two major limitations of all chemotherapeutic agents. Ligand-conjugated nanomedicine is the most versatile approach for targeted cancer therapy. Attaching a targeting ligand to the nanoparticle surface increases drug concentration at the desired sites, decreases the dose needed and lessens side effects. The subject of this patent evaluation describes the preparation of a therapeutic nanosuspension of an anticancer drug, docetaxel (DTX). The nanoparticle matrix comprised a polylactic acid-polyethylene glycol block copolymer (PLA-PEG). The nanoparticles were actively directed towards prostate-specific membrane antigen (PSMA) over-expressing cancer cells using a targeting ligand S,S-2-{3-[1-carboxy-5-amino-pentyl-]ureido}-pantanedioic acid (GL2). The dose-limiting toxicity and maximum tolerated dose were determined for GL2-conjugated and DTX-loaded polymeric nanosuspensions. The efficacy of nanosuspensions was evaluated in people with various cancer types. The investigators claim the method of preparation of therapeutic nanosuspension, optimized composition of the formulation and dosage regimen for the clinical studies to effectively treat gastroesophageal and breast cancers.
authors.affiliation: a Medicinal Chemistry & Pharmacology Division , CSIR-Indian Institute of Chemical Technology , Hyderabad , India.
authors.forename: Deep
authors.initials: D
authors.lastname: Pooja
authors.affiliation: a Medicinal Chemistry & Pharmacology Division , CSIR-Indian Institute of Chemical Technology , Hyderabad , India.|b Health Innovations Research Institute , RMIT University , Melbourne , Australia.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Kulhari
authors.affiliation: b Health Innovations Research Institute , RMIT University , Melbourne , Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.affiliation: a Medicinal Chemistry & Pharmacology Division , CSIR-Indian Institute of Chemical Technology , Hyderabad , India.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D000077143:Docetaxel; D016503:Drug Delivery Systems; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism; D006801:Humans; D053758:Nanoparticles; D010330:Patents as Topic; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013535:Suspensions; D043823:Taxoids / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000954:Antigens, Surface; D000970:Antineoplastic Agents; D011108:Polymers; D013535:Suspensions; D043823:Taxoids; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D000077143:Docetaxel; D011092:Polyethylene Glycols; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: Docetaxel; PSMA; dosage regimen; formulation; polymeric nanosuspension