Amphotericin B Loaded Polymeric Nanoparticles for Treatment of Leishmania Infections
Mudassara Saqib1, A Shabbir Ali Bhatti2, Nasir M Ahmad3
1Department of Pharmacology and Therapeutics, Shaikh Zayed Postgraduate Medical Institute and Shaikh Zayed Medical Complex, Lahore 54000, Pakistan.
Abstract:
Fungal infections in immune-compromised patients are an important cause of mortality and morbidity. Amphotericin B (Amp B) is considered a powerful fungicidal drug but its clinical usage has certain limitations when administered intravenously due to its toxicity and poor solubility. In consideration of such challenges, in cutaneous leishmaniasis, the topical application of Amp B can be a safer option in many aspects. Thus, herein, biopolymer of polycaprolactone (PCL) nanoparticles (NPs) were developed with the loading of Amp B by nanoprecipitation for the treatment of topical leishmanial infections. Various parameters, such as concentration of PCL and surfactant Poloxamer 407, were varied in order to optimize the formation of nanoparticles for the loading of Amp B. The optimized formulation exhibited a mean hydrodynamic particle size of 183 nm with a spherical morphology and an encapsulation efficiency of 85%. The applications of various kinetic models reveal that drug release from nanoformulation follows Korsmeyer-Peppas kinetics and has a high diffusion exponent at a physiological pH of 7.4 as well a skin relevant pH = 5.5. The activity of the prepared nanoparticles was also demonstrated in Leishmania infected macrophages. The measured IC50 of the prepared nanoparticle formulation was observed to be significantly lower when compared to control free Amp B and AmBisome® for both L. tropica KWH23 and L. donovani amastigotes in order to demonstrate maximum parasite inhibition. The prepared topical nanoformulations are capable of providing novel options for the treatment of leishmaniasis, which can be possible after in vivo assays as well as the establishment of safety profiles.
Insights
Polycaprolactone nanoparticles loaded with Amphotericin B offer a safer topical treatment for leishmaniasis. These nanoparticles show enhanced efficacy against Leishmania parasites compared to conventional Amphotericin B formulations.
Area of Science:
- Pharmaceutical Nanotechnology
- Infectious Diseases
- Drug Delivery Systems
Background:
- Fungal infections pose significant mortality risks, especially in immunocompromised individuals.
- Amphotericin B (Amp B) is a potent antifungal but has limitations like toxicity and poor solubility for intravenous use.
- Topical Amp B offers a safer alternative for cutaneous leishmaniasis, necessitating improved delivery systems.
Purpose of the Study:
- To develop polycaprolactone (PCL) nanoparticles loaded with Amphotericin B (Amp B) for topical leishmaniasis treatment.
- To optimize nanoparticle formulation for enhanced drug loading and controlled release.
- To evaluate the efficacy of the developed nanoformulation against Leishmania parasites.
Main Methods:
- Nanoprecipitation was used to formulate Amp B-loaded PCL nanoparticles, with optimization of PCL and Poloxamer 407 concentrations.
- Particle size, morphology, and encapsulation efficiency were characterized.
- Drug release kinetics were studied at physiological and skin-relevant pH values.
- Antiparasitic activity was assessed in Leishmania-infected macrophages.
Main Results:
- Optimized nanoparticles showed a mean size of 183 nm, spherical morphology, and 85% encapsulation efficiency.
- Drug release followed Korsmeyer-Peppas kinetics with a high diffusion exponent at pH 7.4 and 5.5.
- The Amp B nanoparticles demonstrated significantly lower IC50 values against Leishmania tropica and Leishmania donovani amastigotes compared to free Amp B and AmBisome®.
- The nanoformulation achieved maximum parasite inhibition.
Conclusions:
- Polycaprolactone nanoparticles effectively encapsulate Amphotericin B for topical delivery.
- The developed nanoformulation shows promising enhanced efficacy for treating leishmaniasis.
- Further in vivo studies and safety profiling are required to establish these topical nanoformulations as a viable treatment option.
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