Enhancing the therapeutic landscape of cutaneous leishmaniasis: pegylated liposomal delivery of miltefosine for controlled release and improved efficacy

This study develops and evaluates two oral delivery systems, including miltefosine-loaded polyethylene glycol (PEG)ylated and non-PEGylated liposomal formulations (MT-Lip and MT-PEG-Lip, respectively), for cutaneous leishmaniasis (CL). MT-PEG-Lip nanoparticles displayed nanoscale sizes, negative zeta potentials, and homogenous populations (259 +/- 13.6 and 248 +/- 13.8 nm; -28 +/- 1.6 and -13 +/- 0.8 mV; polydispersity index (PDI) of 0.272 +/- 0.014 and 0.279 +/- 0.013 for MT-Lip and MT-PEG-Lip, respectively). Morphological evaluations confirmed uniform, spherical particles with smooth surfaces. PEGylation enhanced sustained drug release, vital for prolonged therapeutic effects. MT-Lip released 92.7 % and 70.5 % of the drug at pHs 1.2 and 6.8 after 72 h, while MT-PEG-Lip exhibited 69.8 % and 57.3 %, respectively. Stability tests over three months showed slight changes, affirming resilience. In vitro, MT-PEG-Lip demonstrated superior antileishmanial effects (half-maximal inhibitory concentration (IC50) for MT, MT-Lip, MT-PEG-Lip: 73.6, 23.7, and 9 mu M against promastigote, and 86.1, 46.6, and 26.8 mu M against amastigote, respectively). In vivo, MT-PEG-Lip significantly reduced lesion size (7.8- and 2.1-fold compared to MT and MT-Lip, respectively) and parasite burden (2.8- and 1.8-fold compared to MT and MT-Lip, respectively) in Leishmania major (L. major)-infected BALB/c mice. Histopathological assessments confirmed the safety of liposomal formulations, establishing MT-PEG-Lip as an efficient drug delivery platform for targeted CL treatment, addressing challenges in drug delivery and efficacy.