Transdermal microneedle-mediated delivery of polymeric lamivudine-loaded nanoparticles

Background: The goal of this study was to develop a novel drug delivery system (NDDS) of lamivudine (LAM) to overcome some drawbacks associated with LAM short half-life. To fulfill this goal, polymeric LAM-loaded nanoparticles were prepared and their transdermal deliveries via passive and microneedles (MNs)-mediated transport were investigated. Methods: First, nanoparticles were prepared by double emulsion-solvent evaporation method using polylactic-co-glycolic acid (PLGA) and bovine serum albumin (BSA) as a polymer and a stabilizer respectively. Two different concentrations of LAM (10 and 20 mg/ml) were used for preparing LAM-loaded nanoparticles (NP10 and NP20 respectively). After that, the prepared nanoparticles were characterized with regard to their particle size (PZ), polydispersity index (PDI), zeta potential (ZP), percent yield (%Yield), morphology, drug loading capacity (%LC), and entrapment efficiency (%EE). Then, in vitro release of LAM from the LAM-loaded nanoparticles was studied and physical stability of the optimized LAM-loaded nanoparticles (NP20) was examined. Finally, permeation of NP20 and LAM solution across plain and MNs-treated excised rabbit skin was investigated. Results: The particle size of the prepared nanoparticles ranged from 152.87±1.27 nm to 196.67±1.74 nm, the PDI ranged from 0.089±0.01 to 0.145±0.03 and the ZP range was from -42.2±7.35 mV to -47.5±6.55 mV. All nanoparticles have distinct spherical shapes with smooth surface and thick shells of the BSA. The entrapment efficiencies of the LAM-loaded nanoparticles were 23.01±4.75% and 26.31±2.8%. A biphasic pattern of drug release was observed in the in vitro release studies with initially faster release profile followed by prolonged release for extended time. The physical stability assessment of NP20 suspension showed that no significant variation of PZ, PDI and ZP could be detected during the storage period of six months. The steady state flux values of the LAM-loaded NP20 across untreated skin and the MNs-treated skin were 7.49±1.46 μg.cm-2.hr-1 and 15.77±1.5 μg.cm-2.hr-1 respectively. Also, the permeation study showed the possibility of transdermal delivery of the LAM-loaded nanoparticles. In the same time, this delivery could be enhanced significantly by MNs-pretreatment of skin. The steady state flux of the LAM-loaded NP20 across the MNs-treated skin was significantly greater than that of passive transport across untreated skin. Conclusions: Polymeric LAM-loaded nanoparticles could serve as a potential NDDS for the sustained transdermal delivery. The steady state flux could be enhanced by more than two folds using the MNsmediated transport.