title: Assessing the physical-chemical properties and stability of dapivirine-loaded polymeric nanoparticles.
abstract: Nanocarriers may provide interesting delivery platforms for microbicide drugs and their characterization should be addressed early in development. Differently surface-engineered dapivirine-loaded, poly(epsilon-caprolactone) (PCL)-based nanoparticles (NPs) were obtained by nanoprecipitation using polyethylene oxide (PEO), sodium lauryl sulfate (SLS), or cetyltrimethylammonium bromide (CTAB) as surface modifiers. Physical-chemical properties of NP aqueous dispersions were evaluated upon storage at -20-40 °C for one year. NPs presented 170-200 nm in diameter, roundish-shape, low polydispersity index (≤0.18), and high drug association efficiency (≥97%) and loading (≥12.7%). NPs differed in zeta potential, depending on surface modifier (PEO: -27.9 mV; SLS: -54.7 mV; CTAB: +42.4 mV). No interactions among formulation components were detected by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), except for SLS-PCL NPs. Colloidal properties of NPs were lost at -20 °C storage. Negatively charged NPs were stable up to one year at 5-40°C; as for CTAB-PCL NPs, particle aggregation was observed from 30 to 90 days of storage depending on temperature. Colloidal instability affected the in vitro drug release of CTAB-PCL NPs after 360 days. In any case, no degradation of dapivirine was apparent. Overall, PEO-PCL and SLS-PCL NPs presented suitable properties as nanocarriers for dapivirine. Conversely, CTAB-PCL NPs require additional strategies in order to increase stability.
authors.affiliation: CICS - Centro de Investigação em Ciências da Saúde, Department of Pharmaceutical Sciences, Instituto Superior de Ciências da Saúde-Norte, CESPU, Rua Central de Gandra 1317, 4585-116 Gandra, Portugal; Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal. Electronic address: j.dasneves@gmail.com.
authors.forename: José
authors.initials: J
authors.lastname: das Neves
authors.forename: Mansoor
authors.initials: M
authors.lastname: Amiji
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Bahia
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
mesh_terms: D055598:Chemical Phenomena; D004337:Drug Carriers / Q000737:chemistry / Q000592:standards; D004355:Drug Stability; D053758:Nanoparticles / Q000737:chemistry* / Q000592:standards; D011108:Polymers / Q000737:chemistry* / Q000592:standards; D011743:Pyrimidines / Q000737:chemistry* / Q000592:standards
chemical_list: D004337:Drug Carriers; D011108:Polymers; D011743:Pyrimidines; C481671:Dapivirine
keywords: Colloidal stability; Drug release; HIV/AIDS; Microbicides; Poly(epsilon-caprolactone)