title: Chemico-physical investigation of tenofovir loaded polymeric nanoparticles.
abstract: Tenofovir (PMPA), an acyclic nucleoside phosphonate analog, is one of the most important drugs used for the HIV treatment. Unfortunately, several adverse reactions are related to its i.v. administration owing to the saturation of an anionic renal transporter. In order to improve the drug administration, the PMPA was embedded into a new type of nanocarriers based on poly-(D,L-lactide-co-glycolide) (PLGA) and/or chitosan (CH). The strategies for the preparation of nanoparticles (Nps) with a more efficient drug loading respect to the one reported in the literature for PMPA nanoencapsulation were investigated. CH was added in the first inner emulsion or in the external phase during the second emulsion of water/oil/water (W/O/W) Nps. The addition of CH in the first inner emulsion was the most promising technique. The Nps have a Z-average of 230 nm, a Z-potential of -3 mV and an EE% of 15 that was 2.5-3 times higher than that obtained with PLGA Nps or CH Nps. In vitro release studies showed a limited control on drug release in phosphate buffer (pH 7.4) while an initial burst effect followed by a slow drug release was observed in acidic receiving phase (pH 4.6). These results suggest the PLGA/CH Nps should be an effective and attractive anti-HIV drug carrier to study the cellular uptake and drug delivery on target cells such as macrophages.
authors.affiliation: TE.FAR.T.I. Group, Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, Via Campi 183, 41100 Modena, Italy. daniela.belletti@unimore.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Belletti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tosi
authors.forename: Flavio
authors.initials: F
authors.lastname: Forni
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Gamberini
authors.forename: Cecilia
authors.initials: C
authors.lastname: Baraldi
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Vandelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruozi
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D019380:Anti-HIV Agents / Q000737:chemistry*; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry; D063065:Organophosphonates / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D004337:Drug Carriers; D063065:Organophosphonates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan; D000068698:Tenofovir; D000225:Adenine