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Myeloid Cell Isolation from Mouse Skin and Draining Lymph Node Following Intradermal Immunization with Live Attenuated Plasmodium Sporozoites

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Functionally engineered 'hepato-liposomes': Combating liver-stage malaria in a single prophylactic dose.

Megha Marwah¹, Pratik Narain Srivastava², Satish Mishra²

¹Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (East), Mumbai, India.

International Journal of Pharmaceutics

|August 3, 2020

Summary

This study repurposed Decoquinate (DQN) as a safer alternative to primaquine for liver-stage malaria treatment. Targeted delivery using hepatotropic ligands in liposomes demonstrated superior antimalarial efficacy, highlighting improved drug delivery strategies.

Keywords:

ASGPR Decoquinate Glycyrrhetinic acid receptors Infectious diseases Liposomes Liver stage malaria

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Area of Science:

Malariology
Drug Delivery
Hepatocyte Targeting

Background:

Primaquine is the standard for radical malaria treatment but has toxicity concerns.
Experimental drugs show promise but face targeted delivery challenges.
Decoquinate (DQN) is identified as a safer, repurposed drug candidate for liver-stage malaria.

Purpose of the Study:

To develop and evaluate a targeted liposomal delivery system for Decoquinate (DQN).
To assess the efficacy of DQN-loaded hepato-liposomes using two distinct hepatotropic ligands.
To compare the in vitro and in vivo antimalarial performance of the engineered liposomes.

Main Methods:

Synthesis of DQN-loaded liposomes functionalized with two different hepatotropic ligands.
Characterization of liposome properties including loading capacity, morphology, particle size, and freeze-drying stability.
In vitro and in vivo evaluation of antimalarial efficacy in liver-stage malaria models.

Main Results:

Hepato-liposomes showed varied DQN loading capacities without significant changes in physical characteristics.
Both ligand-functionalized liposomes demonstrated superior antimalarial efficacy compared to controls.
Significant antimalarial activity was observed at a low DQN dose of 0.5 mg/kg.
In vivo studies confirmed the functional efficiency and importance of carrier design in liposomal drug delivery.

Conclusions:

Repurposed Decoquinate (DQN) delivered via engineered hepato-liposomes offers a promising, safer alternative for liver-stage malaria treatment.
The choice of hepatotropic ligand significantly influences the in vivo drug delivery efficiency.
Liposomal drug delivery design is crucial for effective antimalarial prophylaxis.