Permeability and in vivo distribution of poly(Ɛ-caprolactone) nanoparticles loaded with zidovudine

Abstract

Zidovudine (AZT) is one of first choice drugs for the treatment of acquired immunodeficiency syndrome (AIDS). Despite its efficacy to control virus replication, the extent of adverse effects and the therapeutic regimen are directly related to patients’ non-compliance. In this work, we evaluated the permeability and in vivo distribution of AZT incorporated into poly(Ɛ-caprolactone), PCL, nanoparticles (AZT-NP) aiming to reduce the normally observed side effects and increase the drug bioavailability. AZT-NP were obtained by interfacial deposition of preformed polymer. The mean diameter of the nanoparticles was 283.4 nm ± 17.0 with a polydispersity index of 0.232 ± 0.073. The nanoparticles presented a zeta potential of − 32.4 mV ± 3.3, entrapment rate of 53.11% ± 9.25, and were stable for at least 7 days. The drug and the polymer showed no incompatibility in thermal analysis. The permeability of AZT across Caco-2 cells was 22-fold higher for AZT-NP compared to the drug solution. The nanoparticles were able to release AZT in vivo after oral administration in mice, and the plasma levels of labeled AZT-NP were higher and more constant when compared to free labeled AZT. Thus, AZT-NP demonstrated superior performance compared to the drug solution in vivo and in vitro, showing the potential of this system for the treatment of AIDS.