Self Assembled Ionically Sodium Alginate Cross-Linked Amphotericin B Encapsulated Glycol Chitosan Stearate Nanoparticles: Applicability in Better Chemotherapy and Non-Toxic Delivery in Visceral Leishmaniasis

• Published in: Pharmaceutical research 2015-05, Vol.32 (5), p.1727-1740
• Main Authors: Gupta, Pramod K., Jaiswal, Anil K., Asthana, Shalini, Verma, Ashwni, Kumar, Vivek, Shukla, Prashant, Dwivedi, Pankaj, Dube, Anuradha, Mishra, Prabhat R.
• Format: Article
• Language: English
• Subjects: Alginates - chemistry; Amphotericin B - administration & dosage; Amphotericin B - pharmacokinetics; Amphotericin B - therapeutic use; Animals; Antiprotozoal Agents - administration & dosage; Antiprotozoal Agents - pharmacokinetics; Antiprotozoal Agents - therapeutic use; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cell Line; Chemotherapy; Chitinase; Chitosan - chemistry; Drug Carriers - chemistry; Drug delivery systems; Glucuronic Acid - chemistry; Hexuronic Acids - chemistry; Ions; Leishmania; Leishmania donovani - drug effects; Leishmaniasis, Visceral - drug therapy; Macrophages - parasitology; Male; Medical Law; Mesocricetus; Nanoparticles; Nanoparticles - chemistry; Pharmacology/Toxicology; Pharmacy; Rats, Wistar; Research Paper; Sodium; Stearates - chemistry
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-014-1571-4

Objectives To investigate the applicability, localization, biodistribution and toxicity of self assembled ionically sodium alginate cross-linked AmB loaded glycol chitosan stearate nanoparticles for effective management of visceral leishmaniasis. Methods Here, we fabricated Amphotericin B (AmB) encapsulated sodium alginate-glycol chitosan stearate nanoparticles (AmB-SA-GCS-NP) using strong electrostatic interaction between oppositely charged polymer and copolymer by ionotropic complexation method. The tagged FAmB-SA-GCS-NP was compared with tagged FAmB for in vitro macrophagic uptake in J774A macrophages and in vivo localization in liver, spleen, lung and kidney tissues. The AmB-SA-GCS-NP and plain AmB were compared for in vitro and in vivo antileishmanial activity, pharmacokinetics, organ distribution and toxicity profiling. Results The morphology of SA-GCS-NP revealed as nanocrystal (size, 196.3 ± 17.2 nm; PDI, 0.216 ± 0.078; zeta potential, (−) 32.4 ± 5.1 mV) by field emission scanning electron microscopy and high resolution transmission electron microscopy. The macrophage uptake and in vivo tissue localization studies shows tagged FAmB-SA-GCS-NP has significantly higher (~1.7) uptake compared to tagged FAmB. The biodistribution study of AmB-SA-GCS-NP showed more localized distribution towards Leishmania infected organs i.e. spleen and liver while lesser towards kidney. The in vitro (IC 50 , 0.128 ± 0.024 μg AmB/ml) and in vivo (parasite inhibition, 70.21 ± 3.46%) results of AmB-SA-GCS-NP illustrated significantly higher ( P