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Current Molecular Pharmacology

Author(s): Paramjot Mehan, Ashish Garg, Kumar Ajay and Neeraj Mishra*

DOI: 10.2174/1874467213999201125220729

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Ligand Decorated Primaquine Loaded Nanocarriers for Liver Targeting for Triggered Anti-Malarial Activity

Page: [412 - 427] Pages: 16

  • * (Excluding Mailing and Handling)

Abstract

Objective: The aim of the current research is to formulate a nano delivery system for effective delivery of primaquine for liver targeting to achieve the potential anti-malarial activity. Another objective of current development is to formulate a lactobionic acid conjugated polyphosphazene based nano delivery of primaquine for liver targeting to distinguish anti-malarial activity.

Method: The particle size, entrapment efficiency, in-vitro drug release pattern, hepatotoxicity, MTT assay, erythrocyte toxicity assay, histopathology study, HepG2 cell uptake study, anti-- malarial study, and organ-distribution was also carried out to estimate the activity and potential features of a nanoparticle system.

Results: The results obtained from the above analysis justify the efficiency and effectiveness of the system. The NMR studies confirm the conjugation pattern and the TEM represents the spherical morphological features of nanoparticles. The controlled release pattern from the in-vitro release study was observed and found to be 73.25% of drug release in 20 hrs and in the nano-size range (61.6± 1.56 nm) by particle size analysis.SGOT level, SGPT, ALP, and Parasitemia level of optimized drug-loaded PEGylated lactobionic acid conjugated polyphosphazene derivatized nanoparticles (FF) was found to lie in the safe range, showing that the formulation is non-toxic to the liver. Primaquine drug-loaded PEGylated lactobionic acid conjugated polyphosphazene polymeric nanoparticles showed higher cell uptake on HepG2 cell lines as compared to the drug-loaded in PEGylated polyphosphazene polymeric nanoparticles and plain drug.Percentage cell viability of drugloaded PEGylated lactobionic acid conjugated polyphosphazene derivatized nanoparticles was decreased by enhancing the concentration of prepared nanoparticle system accessed by MTT assay.

Conclusion: From the studies, it can be concluded that the optimized formulation of drug-loaded PEGylated lactobionic acid conjugated polyphosphazene derivatized nanoparticles showed high liver targeting, least toxicity to the liver, controlled release of the drug, higher anti-malarial activity against hepatocytes at a low dose, more effectiveness, and can be treated as a potential candidate for anti-malarial therapy.

Keywords: Nanoparticles, malaria, hepatotoxicity, organ distribution, primaquine, lactobionic acid, histopathology.

Graphical Abstract

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