Abstract The remarkable ability of the human immunodeficiency virus (HIV) to evade the host's immune system and conventional antiretroviral therapy, has posed significant challenges in achieving complete eradication of the virus in people living with HIV (PLWHIV). However, nanotechnology has emerged as promising avenue for addressing some of the obstacles associated with the use of antiretroviral drugs by modifying drug molecules in nanoscale dimensions. Hence, the present study explores the utilization of poly(epsilon‐caprolactone) (PCL) as a carrier for encapsulating tenofovir disoproxil fumarate (TDF), offering an alternative treatment approach for HIV infection. TDF‐loaded polymeric nanoparticles were successfully prepared using double emulsion solvent evaporation technique and characterized. The characterization of TDF‐loaded polymeric nanoparticles at varied drug to polymer ratios showed that TDF was loaded in PCL with an encapsulation efficiency and drug loading capacity in the range of 23–46% and 4.8–19.9%, respectively. Of note, the neutralization efficacy of TDF‐loaded polymeric nanoparticles was more improved compared to free TDF. Encapsulation of TDF with PCL did not hinder the antiviral activity of TDF against HIV‐1 infection but rather enhanced its potency.
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