Antiretroviral Solid Drug Nanoparticles with Enhanced Oral Bioavailability: Production, Characterization, and In Vitro-In Vivo Correlation

Tom McDonald, Marco Giardiello, Philip Martin, Marco Siccardi, Neill Liptrott, Darren Smith, Phill Roberts, Paul Curley, Alessandro Schipani, Saye Khoo, James Long, Alison Foster, Steven Rannard, Andrew Owen

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

Abstract

Nanomedicine strategies have produced many commercial products. However, no orally dosed HIV nanomedicines are available clinically to patients. Although nanosuspensions of drug particles have demonstrated many benefits, experimentally achieving >25 wt% of drug relative to stabilizers is highly challenging. In this study, the emulsion-templated freeze-drying technique for nanoparticles formation is applied for the first time to optimize a nanodispersion of the leading non-nucleoside reverse transcriptase inhibitor efavirenz, using clinically acceptable polymers and surfactants. Dry monoliths containing solid drug nanoparticles with extremely high drug loading (70 wt% relative to polymer and surfactant stabilizers) are stable for several months and reconstitute in aqueous media to provide nanodispersions with z-average diameters of 300 nm. The solid drug nanoparticles exhibit reduced cytoxicity and increased in vitro transport through model gut epithelium. In vivo studies confirm bioavailability benefits with an approximately four-fold higher pharmacokinetic exposure after oral administration to rodents, and predictive modeling suggests dose reduction with the new formulation may be possible.
Original languageEnglish
Pages (from-to)400-411
JournalAdvanced healthcare materials
Volume3
Issue number3
DOIs
Publication statusPublished - Mar 2014

Fingerprint

Dive into the research topics of 'Antiretroviral Solid Drug Nanoparticles with Enhanced Oral Bioavailability: Production, Characterization, and In Vitro-In Vivo Correlation'. Together they form a unique fingerprint.

Cite this