Development of dextrin-amphotericin B formulations for the treatment of Leishmaniasis

Silva-Carvalho, Ricardo; Fidalgo, J.; Melo, Karoline Rachel Teodosio; Queiroz, Moacir Fernandes; Leal, S.; Rocha, H.A.; Cruz, Tânia; Parpot, Píer; Tomás, Ana M.; Gama, Miguel

doi:10.1016/j.ijbiomac.2020.03.019

Cited by 18 publications

(22 citation statements)

References 72 publications

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“…Hemolysis test assesses the percentage of erythrocyte rupture. Both the protocol and the animal's blood were derived from Silva-Carvalho et al (2020) 5 . We used ordinary blood samples (dog) from a blood bank.…”

Section: Hemolysis Testmentioning

confidence: 99%

“…This system has advantages such as nano scale, high stability, good dispersion in water, low toxicity, with excellent cost-bene t and does not use solvents. In the literature, there are several works using different types of polymers, such as dextrin 5 , gum arabic 6 , albumin 7 and alginate 8 . Alginate (Alg) is a polymer extracted from natural sources, widely used in the pharmaceutical area and in tissue engineering.…”

Section: Introductionmentioning

confidence: 99%

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Alginate-Amphothericin B Nanocomplexes Covered By Nanocrystals From Bacterial Cellulose: Physico-Chemical Characterization And In Vitro Toxicity

Soeiro

Silva-Carvalho

Martins

et al. 2021

Preprint

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Amphotericin B (AmB) is a drug with anti-leishmanial and anti-fungal ability, but it has low water solubility and permeability, limiting its therapeutic use. Therefore, the incorporation of AmB into nanostructured systems could be profit. Nanostructured systems without surfactants have pharmacotechnical advantages such as amplify the water solubility and decrease the toxicity. For this reason, the present study aimed to produce a nanocomplex of alginate (Alg) with AmB covered by NCC in order to decrease the toxicity of AmB. This straightforward process allowed to obtain water soluble particles Furthermore, the ionic adsorption of the NCC into the Alg-AmB nanocomplex surface was confirmed by an increase in the particle size and a small surface charge decrease. The amorphous inclusion of AmB complex into the polysaccharide chain network in both formulations. AmB in the nanocomplexes was in supper-aggregated form and showed good biocompatibility, being significantly less cytotoxic in vitro against kidney cells and significantly less hemolytic compared to the free-drug. The results indicated the Alg-AmB nanocomplex can be considered a non-toxic alternative to improve the AmB therapeutic effect. Furthermore, NCC coating of the nanocomplexes brought additional protection to the system without compromised the advantages attributed to the developed formulation.

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Section: Hemolysis Testmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alginate-Amphothericin B Nanocomplexes Covered By Nanocrystals From Bacterial Cellulose: Physico-Chemical Characterization And In Vitro Toxicity

Soeiro

Silva-Carvalho

Martins

et al. 2021

Preprint

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“…The hemolysis test assesses the percentage of erythrocyte rupture. Both the protocol and the animal's blood were derived from the work of Silva-Carvalho et al (2020) (5). Blood was collected from a healthy dog with the owners' consent on everything with EDTA.…”

Section: Hemolysis Testmentioning

confidence: 99%

“…This system has advantages such as nano scale, high stability, good dispersion in water, low toxicity, with excellent cost-bene t and does not use solvents. In the literature, there are several works that use different types of polymers, such as dextrin (5), gum arabic (6), albumin (7) and alginate (8). For this research, we chose to work with alginate.…”

Section: Introductionmentioning

confidence: 99%

Alginate-amphothericin B Nanocomplexes Covered by Nanocrystals From Bacterial Cellulose: Physico-chemical Characterization and in Vitro Toxicity

Vs¹,

Silva-Carvalho²,

Martins³

et al. 2020

Preprint

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Background: Nanostructured systems free of surfactants have pharmacotechnical and biopharmaceutical advantages, in addition to being a green process. Amphotericin B (AmB) is a drug with anti-leishmanial and anti-fungal potential, but its low water solubility and permeability limit its therapeutic use. Therefore, it could profit from being incorporated into nanostructured systems. In the present study, a self-assembled nanocomplex of alginate (Alg), a polysaccharide extracted from natural sources that can be used in the pharmaceutical area, with AmB was produced in order to improve the limited therapeutic use of this drug (Alg-AmB). Further, as a reinforcing component, cellulose nanocrystals (NCC) were ionically adsorbed into the surface of the nanocomplex systems (Alg-AmB + NCC). Results: Despite some polydispersity (0.523 ± 0.073), this straightforward process allowed to obtain water soluble particles with a hydrodynamic size of 258.87 ± 10.41 nm and charge of -62.93 ± 2.02 mV. Furthermore, the ionic adsorption of the NCC into the Alg-AmB nanocomplex surface was confirmed by an increase in the particle size (466.3 ± 17.57 nm) and a small surface charge decrease (-55.75 ± 1.23 mV). The amorphous inclusion complex of AmB into the polysaccharide chain network in both formulations was confirmed by DSC and FTIR. AmB in the nanocomplexes was in supper-aggregated form and showed good biocompatibility, being significantly less cytotoxic in vitro against kidney cells and significantly less hemolytic comparatively to the free-drug. Conclusions: The results were indicated the Alg-AmB nanocomplex can be considered an economical, non-toxic alternative to improve the AmB therapeutic effect. Furthermore, NCC coating of the nanocomplexes brought additional protection to the system without compromised the advantages attributed to the developed formulation.

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“…AmB plays a crucial role in inhibiting the growth of fungi by affecting the permeability of cell membranes and thus was used to effectively treat invasive fungal infections. In order to reduce the toxic and side effects of AmB, some strategies have been developed, including water-soluble dextrin-AmB (Dex-AmB) formulations and AmB loaded pluronic F127 (PF 127) micelles which was then coated with chitosan (Cs-PF-AmB-M) [6,7]. As AmB is a complex compound, the synthesis of AmB by chemical way is extremely difficult.…”

Section: Introductionmentioning

confidence: 99%

Comparative metabolomics analysis of amphotericin B high-yield mechanism for metabolic engineering

et al. 2021

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Background The polyene macrocyclic compound amphotericin B (AmB) is an important antifungal antibiotic for the clinical treatment of invasive fungal infections. To rationally guide the improvement of AmB production in the main producing strain Streptomyces nodosus, comparative metabolomics analysis was performed to investigate the intracellular metabolic changes in wild-type S. nodosus ZJB20140315 with low-yield AmB production and mutant S. nodosus ZJB2016050 with high-yield AmB production, the latter of which reached industrial criteria on a pilot scale. Results To investigate the relationship of intracellular metabolites, 7758 metabolites were identified in mutant S. nodosus and wildtype S. nodosus via LC–MS. Through analysis of metabolism, the level of 26 key metabolites that involved in carbon metabolism, fatty acids metabolism, amino acids metabolism, purine metabolism, folate biosynthesis and one carbon pool by folate were much higher in mutant S. nodosus. The enrichment of relevant metabolic pathways by gene overexpression strategy confirmed that one carbon pool by folate was the key metabolic pathway. Meanwhile, a recombinant strain with gene metH (methionine synthase) overexpressed showed 5.03 g/L AmB production within 120 h fermentation, which is 26.4% higher than that of the mutant strain. Conclusions These results demonstrated that comparative metabolomics analysis was an effective approach for the improvement of AmB production and could be applied for other industrially or clinically important compounds as well.

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Development of dextrin-amphotericin B formulations for the treatment of Leishmaniasis

Cited by 18 publications

References 72 publications

Alginate-Amphothericin B Nanocomplexes Covered By Nanocrystals From Bacterial Cellulose: Physico-Chemical Characterization And In Vitro Toxicity

Alginate-Amphothericin B Nanocomplexes Covered By Nanocrystals From Bacterial Cellulose: Physico-Chemical Characterization And In Vitro Toxicity

Alginate-amphothericin B Nanocomplexes Covered by Nanocrystals From Bacterial Cellulose: Physico-chemical Characterization and in Vitro Toxicity

Comparative metabolomics analysis of amphotericin B high-yield mechanism for metabolic engineering

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