Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations

Abstract

Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and -20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1.

Figure 1

TEM image of PLGA-CS-NVP-LMV NPs. NPs following fabrication (a, b); after 1 year, stored at room temperature (c); after 1 year, stored at −70°C (d); lyophilized with 10% sucrose, stored at 4°C (e); and stored at −20°C in 10% sucrose but nonlyophilized (f).

Figure 2

Log-normal distribution for PLGA-CS-NVP-LMV NPs (Sample 3.4). MSD histogram in red.

Figure 3

Size and PDI stability of NPs at different storage conditions; (a), (b), (c), and (f) were stable while (d) and (e) were unstable. Size is maintained after lyophilization (g and h). (a) PLGA-CS-NVP-LMV NPs stored at room temperature; (b) PLGA-CS-NVP NPs stored at room temperature; (c) PLGA-CS-LMV NPs lyophilized with 10% sucrose and stored at 4°C; (d) PLGA-CS-NVP-LMV NPs lyophilized without sucrose and stored at 4°C; (e) PLGA-CS-LMV NPs lyophilized without sucrose and stored at 4°C; (f) PLGA-CS-NVP NPs in 10% sucrose stored at −20°C; (g) PLGA-CS-NVP-LMV NPs lyophilized in 10% sucrose; (h) PLGA-CS-NVP NPs lyophilized in 10% sucrose.

Figure 4

Release of LMV and NVP from PLGA-CS-NVP-LMV NPs at 37°C in PBS pH 7.2 (mean n = 3).

Figure 5

Release of LMV and NVP from PLGA-CS-NVP-LMV NPs at 4°C in PBS pH 7.2 (mean n = 3).

Figure 6

Release kinetics of PLGA-CS-LMV NPs in pH 5 at 37°C. Data are fit using the zero-order model.

Figure 7

Release kinetics of PLGA-CS-NVP NPs in pH 7.2 at 37°C. Data are fit using the first-order model.