Poly(ε-caprolactone), Eudragit® RS 100 and poly(ε-caprolactone)/Eudragit® RS 100 blend submicron particles for the sustained release of the antiretroviral efavirenz.

The design of simple and scalable drug delivery systems to target the central nervous system (CNS) could represent a breakthrough in the addressment of the HIV-associated neuropathogenesis. The intranasal (i.n.) route represents a minimally invasive strategy to surpass the blood-brain barrier, though it demands the use of appropriate nanocarriers bearing high drug payloads and displaying sufficiently long residence time. The present work explored the development of submicron particles made of poly(ε-caprolactone) (PCL), Eudragit(®) RS 100 (RS a copolymer of ethylacrylate, methylmethacrylate and methacrylic acid esterified with quaternary ammonium groups) and their blends, loaded with the first-choice antiretroviral efavirenz (EFV) as an approach to fine tune the particle size and the release kinetics. Particles displaying hydrodynamic diameters between 90 and 530 nm were obtained by two methods: nanoprecipitation and emulsion/solvent diffusion/evaporation. In general, the former resulted in smaller particles and narrower size distributions. The encapsulation efficiency was greater than 94%, the drug weight content approximately 10% and the yield in the 72.5-90.0% range. The highly positive surface (>+30 mV) rendered the suspensions physically stable for more than one month. In vitro release assays indicated that the incorporation of the poly(methacrylate) into the composition reduced the burst effect and slowed the release rate down with respect to pure poly(ε-caprolactone) particles. The analysis of the release profile indicated that, in all cases, the kinetics adjusted well to the Higuchi model with R(adj)(2) values >0.9779. These findings suggested that the release was mainly controlled by diffusion. In addition, when data were analyzed by the Korsmeyer-Peppas model, n values were in the 0.520-0.587 range, indicating that the drug release was accomplished by the combination of two phenomena: diffusion and polymer chain relaxation. Based on ATR/FT-IR analysis that investigated drug/polymer matrix interactions, the potential role of the hydrophobic interactions of C-F groups of EFV with carbonyl groups in the backbone of PCL and poly(methacrylate) could be ruled out. The developed EFV-loaded particles appear as a useful platform to investigate the intranasal administration to increase the bioavailability in the CNS.