Research Article
Novel nano-sized chitosan amphotericin B formulation with considerable improvement against Leishmania major
Published Online:22 Nov 2018https://doi.org/10.2217/nnm-2018-0063
Abstract
Aim: Improvement in the treatment of Leishmania major's pathological effects through increasing the dose of amphotericin B loaded into nanochitosan. Materials & methods: The phase separation method was used for nanochitosan synthesis and amphotericin loading. Also a novel solvent was designed and the nanodrug efficacy was evaluated in vitro and in vivo (pathology) environments. Results: The drug loading efficiency of 90%, along with slow drug-release with cellular uptake of 98.6% was achieved. The novel solvent was composed of 10% acetic acid, and it was succeeded to dissolve AK10 mg/kg. Also, AK10 mg/kg had no side effects in in vitro and in vivo environments. In addition, the complete wound healing and parasite inhibition were achieved by using AK10 mg/kg in terms of improvement the treatment indicators. Conclusion: Increasing the therapeutic dose of AK to 10 mg/kg caused the successful treatment of L. major's pathological effects in in vitro and in vivo environments.
Keywords:
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1 An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis. Int. J. Nanomedicine 9, 5341–5353 (2014). •• In this study nano amphotericin chitosan (AK) 1 mg/kg was used for leishmaniasis treatment (Leishmania amazonensis) in vivo environment and its in vivo toxicity was evaluated by pathological studies. Also, the functional mechanism of nanochitosan was thoroughly explained.
- 2 . Hexadecylphosphocholine (Miltefosine) stabilized chitosan modified Ampholipospheres as prototype co-delivery vehicle for enhanced killing of L. donovani. Int. J. Biol. Macromolecules 105, 625–637 (2017). •• In this study, AK1 mg/kg was used for leishmaniasis treatment (Leishmania donovani) in vivo environment in hamster model. The nanodrug size was 332 nm, and synthesized by polyelectrolyte complex. Also, the functional mechanism of nanochitosan was thoroughly explained.
- 3 Chitosan-assisted immunotherapy for intervention of experimental leishmaniasis via amphotericin B-loaded solid lipid nanoparticles. Appl. Biochem. Biotechnol. 174(4), 1309–1330 (2014). • In this study, AK efficacy was evaluated only in vitro environment against L. donovani. However, its toxicity was evaluated in vivo environment by using pathological studies and AK1 mg/kg.
- 4 Development of 4-sulfated N-acetyl galactosamine anchored chitosan nanoparticles: a dual strategy for effective management of leishmaniasis. Colloids Surf. B Biointerfaces 136, 150–159 (2015). •• In this study, AK1 mg/kg was used for leishmaniasis treatment (L. donovani) in vivo environment. The nanodrug size was 332 nm and it was synthesized by polyelectrolyte complex method. Drug loading efficiency of 63% was achieved.
- 5 . Iranpharma: A Comprehensive Textbook of Drug information. Teimourzadeh Press, Tehran, Iran (2002).
- 6 Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis. Nanomedicine 12(2), 99–115 (2017). • In this study, AK1 mg/kg was used for leishmaniasis (L. donovani) treatment in vivo environment. The nanodrug size was 362 nm with the drug loading efficiency of 47%.
- 7 . Fabrication, characterization and cytotoxicity studies of ionically cross-linked docetaxel loaded chitosan nanoparticles. Carbohydr. Polym. 137, 65–74 (2016).
- 8 . Chitosan – a versatile semi-synthetic polymer in biomedical applications. Prog. Polym. Sci. 36(8), 981–1014 (2011).
- 9 . Nanostructured delivery systems with improved leishmanicidal activity: a critical review. Int. J. Nanomedicine 12, 5289 (2017).
- 10 Chitosan coated PluronicF127 micelles for effective delivery of Amphotericin B in experimental visceral leishmaniasis. Int. J. Biol. Macromolecules 105, 1220–1231 (2017). • In this study AK1 mg/kg was used for leishmaniasis treatment (L. donovani) in vivo environment and its in vivo toxicity was evaluated by pathological studies and blood tests. Also, the drug loading efficiency was equal to 63%.
- 11 . Synthesis of nano-niosomal deferoxamine and evaluation of its functional characteristics to apply as an iron-chelating agent. Can. J. Chem. Eng. 96(1), 107–112 (2018).
- 12 Smart bomb AS1411 aptamer-functionalized/PAMAM dendrimer nanocarriers for targeted drug delivery in the treatment of gastric cancer. Clin. Exp. Pharmacol. Physiol. 44(1), 41–51 (2017).
- 13 Coadminstration of L. major amastigote class I nuclease (rLmaCIN) with LPD nanoparticles delays the progression of skin lesion and the L. major dissemination to the spleen in BALB/c mice-based experimental setting. Acta Tropica 159, 211–218 (2016).
- 14 . Effect of amphotericin B nanodisks on Leishmania major infected mice. Pharmaceutica. Analytica. Acta 5, 1–13 (2014).
- 15 . Administration of monoclonal anti-IFN-γ antibodies in vivo abrogates natural resistance of C3H/HeN mice to infection with Leishmania major. J. Immunol. 143(1), 266–274 (1989).
- 16 . Stomach-specific anti-H. pylori therapy. I: preparation and characterization of tetracyline-loaded chitosan microspheres. Int. J. Pharmaceutics 235(1–2), 87–94 (2002).
- 17 . Immunoadjuvant chemotherapy of visceral leishmaniasis in hamsters using amphotericin B-encapsulated nanoemulsion template-based chitosan nanocapsules. Antimicrob. Agents Chemother. 57(4), 1714–1722 (2013). • In this study, AK1 mg/kg was used for leishmaniasis treatment in vivo environment (Hamster). Drug loading efficiency of 50% was achieved. They used the strain of L. donovani in their study.
- 18 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. Pharm. Res. 32(5), 1727–1740 (2015). • In this study, AK1mg/kg was used for leishmaniasis treatment in vivo environment (Hamster). The in vivo toxicity was evaluated in vivo environment by using pathological studies. They used L. donovani.
- 19 . Controlled release. In: Encyclopedia of Polymeric Nanomaterials. S Kobayashi, K Müllen. Springer-Verlag Berlin Heidelberg, Berlin Heidelberg, 439–449 (2015).
- 20 Novel targeting using nanoparticles: an approach to the development of an effective anti-leishmanial drug-delivery system. Int. J. Nanomed. 9, 877–890 (2014).
