Novel Nanosized Chitosan-Betulinic Acid Against Resistant Leishmania Major and First Clinical Observation of Such Parasite in Kidney

Overview

Journal Sci Rep

Specialty Science

Date 2018 Aug 8

PMID 30082741

Citations 19

Authors

Tahereh Zadeh Mehrizi

Mehdi Shafiee Ardestani

Mostafa Haji Molla Hoseini

Ali Khamesipour

Nariman Mosaffa

Amitis Ramezani

Affiliations

Soon will be listed here.

Abstract

Regarding the antiparasitic effects of Betulinic acid (B) against Leishmaniasis, it was loaded into nanochitosan (K) for the first time in order to improve its therapeutic effects and decrease its side effects for the treatment of Leishmania major-infected Balb/c mice. Improvement the therapeutic efficacy of Bas an anti-leishmania agent through increasing the effective dose was achieved by using a novel solvent and phase separation method for K synthesis. The synthesized K with the size of 102 nm and Betulinic acid-nanochitosan (BK) with the size of 124 nm and drug loading efficiency of 93%, cellular uptake of 97.5% with the slow drug release pattern was prepared. To increase the therapeutic dose, a modified 10% acetic acid solvent was used. The in vitro and in vivo results showed that the nanodrug of BK was non toxic by 100% and BK20 mg/kg could completely performed the wound healing and inhibit the parasite in a large extent (P ˂ 0.001) compared to other groups. Therefore, BK could be considered as an alternative regimen for treatment of L. major.

Citing Articles

Zinc nanoparticles coated with peppermint () essential oil: a nanoformulated compound with anti-leishmanial activity.

Zangiyani M, Livani F, Faridnia R, Kalani H J Parasit Dis. 2025; 49(1):103-110.

PMID: 39975615 PMC: 11832969. DOI: 10.1007/s12639-024-01741-8.

Immunotherapeutic Strategies as Potential Treatment Options for Cutaneous Leishmaniasis.

Lafleur A, Daffis S, Mowbray C, Arana B Vaccines (Basel). 2024; 12(10).

PMID: 39460345 PMC: 11511131. DOI: 10.3390/vaccines12101179.

Chemical Characterization and Leishmanicidal Activity In Vitro and In Silico of Natural Products Obtained from Leaves of (L.) H. Rob (Asteraceae).

Froes Y, Araujo J, Goncalves J, Oliveira M, Everton G, Mouchrek Filho V Metabolites. 2023; 13(2).

PMID: 36837904 PMC: 9967733. DOI: 10.3390/metabo13020285.

Plant Bioactive Ingredients in Delivery Systems and Nanocarriers for the Treatment of Leishmaniasis: An Evidence-Based Review.

Alanazi A, Said M Iran J Parasitol. 2023; 17(4):458-472.

PMID: 36694570 PMC: 9825702. DOI: 10.18502/ijpa.v17i4.11272.

Vaccination with Formulation of Nanoparticles Loaded with Leishmania amazonensis Antigens Confers Protection against Experimental Visceral Leishmaniasis in Hamster.

Gonzalez M, Goncalves A, Ottino J, Leite J, Resende L, Melo-Junior O Vaccines (Basel). 2023; 11(1).

PMID: 36679956 PMC: 9863486. DOI: 10.3390/vaccines11010111.

References

Ahmed T, Aljaeid B . Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery. Drug Des Devel Ther. 2016; 10:483-507. PMC: 4734734. DOI: 10.2147/DDDT.S99651. View

Yogeeswari P, Sriram D . Betulinic acid and its derivatives: a review on their biological properties. Curr Med Chem. 2005; 12(6):657-66. DOI: 10.2174/0929867053202214. View

Saneja A, Kumar R, Singh A, Dubey R, Mintoo M, Singh G . Development and evaluation of long-circulating nanoparticles loaded with betulinic acid for improved anti-tumor efficacy. Int J Pharm. 2017; 531(1):153-166. DOI: 10.1016/j.ijpharm.2017.08.076. View

Jain A, Thakur K, Sharma G, Kush P, Jain U . Fabrication, characterization and cytotoxicity studies of ionically cross-linked docetaxel loaded chitosan nanoparticles. Carbohydr Polym. 2015; 137:65-74. DOI: 10.1016/j.carbpol.2015.10.012. View

Abamor E . Antileishmanial activities of caffeic acid phenethyl ester loaded PLGA nanoparticles against Leishmania infantum promastigotes and amastigotes in vitro. Asian Pac J Trop Med. 2017; 10(1):25-34. DOI: 10.1016/j.apjtm.2016.12.006. View

Asthana S, Jaiswal A, Gupta P, Pawar V, Dube A, Chourasia M . Immunoadjuvant chemotherapy of visceral leishmaniasis in hamsters using amphotericin B-encapsulated nanoemulsion template-based chitosan nanocapsules. Antimicrob Agents Chemother. 2013; 57(4):1714-22. PMC: 3623311. DOI: 10.1128/AAC.01984-12. View

Ribeiro T, Franca J, Fuscaldi L, Santos M, Duarte M, Lage P . 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. 2014; 9:5341-53. PMC: 4242406. DOI: 10.2147/IJN.S68966. View

Sreeprasad T, Maliyekkal S, Lisha K, Pradeep T . Reduced graphene oxide-metal/metal oxide composites: facile synthesis and application in water purification. J Hazard Mater. 2010; 186(1):921-31. DOI: 10.1016/j.jhazmat.2010.11.100. View

Van Bocxlaer K, Yardley V, Murdan S, Croft S . Drug permeation and barrier damage in Leishmania-infected mouse skin. J Antimicrob Chemother. 2016; 71(6):1578-85. DOI: 10.1093/jac/dkw012. View

10.

Morakul B, Suksiriworapong J, Chomnawang M, Langguth P, Junyaprasert V . Dissolution enhancement and in vitro performance of clarithromycin nanocrystals produced by precipitation-lyophilization-homogenization method. Eur J Pharm Biopharm. 2014; 88(3):886-96. DOI: 10.1016/j.ejpb.2014.08.013. View

11.

Ribeiro T, Chavez-Fumagalli M, Valadares D, Franca J, Rodrigues L, Duarte M . Novel targeting using nanoparticles: an approach to the development of an effective anti-leishmanial drug-delivery system. Int J Nanomedicine. 2014; 9:877-90. PMC: 3931713. DOI: 10.2147/IJN.S55678. View

12.

Tripathi P, Jaiswal A, Dube A, Mishra P . Hexadecylphosphocholine (Miltefosine) stabilized chitosan modified Ampholipospheres as prototype co-delivery vehicle for enhanced killing of L. donovani. Int J Biol Macromol. 2017; 105(Pt 1):625-637. DOI: 10.1016/j.ijbiomac.2017.07.076. View

13.

Corware K, Harris D, Teo I, Rogers M, Naresh K, Muller I . Accelerated healing of cutaneous leishmaniasis in non-healing BALB/c mice using water soluble amphotericin B-polymethacrylic acid. Biomaterials. 2011; 32(31):8029-39. PMC: 3168736. DOI: 10.1016/j.biomaterials.2011.07.021. View

14.

Irby D, Du C, Li F . Lipid-Drug Conjugate for Enhancing Drug Delivery. Mol Pharm. 2017; 14(5):1325-1338. PMC: 5477224. DOI: 10.1021/acs.molpharmaceut.6b01027. View

15.

Tenzer S, Docter D, Kuharev J, Musyanovych A, Fetz V, Hecht R . Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat Nanotechnol. 2013; 8(10):772-81. DOI: 10.1038/nnano.2013.181. View

16.

Tripathi P, Dwivedi P, Khatik R, Jaiswal A, Dube A, Shukla P . Development of 4-sulfated N-acetyl galactosamine anchored chitosan nanoparticles: A dual strategy for effective management of Leishmaniasis. Colloids Surf B Biointerfaces. 2015; 136:150-9. DOI: 10.1016/j.colsurfb.2015.08.037. View

17.

Mohammadzadeh P, Cohan R, Ghoreishi S, Bitarafan-Rajabi A, Shafiee Ardestani M . AS1411 Aptamer-Anionic Linear Globular Dendrimer G2-Iohexol Selective Nano-Theranostics. Sci Rep. 2017; 7(1):11832. PMC: 5605695. DOI: 10.1038/s41598-017-12150-8. View

18.

Chowdhury A, Mandal S, Goswami A, Ghosh M, Mandal L, Chakraborty D . Dihydrobetulinic acid induces apoptosis in Leishmania donovani by targeting DNA topoisomerase I and II: implications in antileishmanial therapy. Mol Med. 2003; 9(1-2):26-36. PMC: 1430381. View

19.

Belosevic M, Finbloom D, van der Meide P, Slayter M, Nacy C . Administration of monoclonal anti-IFN-gamma antibodies in vivo abrogates natural resistance of C3H/HeN mice to infection with Leishmania major. J Immunol. 1989; 143(1):266-74. View

20.

Meira C, Barbosa-Filho J, Lanfredi-Rangel A, Guimaraes E, Moreira D, Soares M . Antiparasitic evaluation of betulinic acid derivatives reveals effective and selective anti-Trypanosoma cruzi inhibitors. Exp Parasitol. 2016; 166:108-15. DOI: 10.1016/j.exppara.2016.04.007. View