Chemico-physical investigation of tenofovir loaded polymeric nanoparticles

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.