4.0 Article

Thermal responsive poly-N-isopropylacrylamide/galactomannan copolymer nanoparticles as a potential amphotericin delivery carrier

出版社

ELSEVIER
DOI: 10.1016/j.carpta.2021.100126

关键词

Galactomannan; Poly(N-isoproprylacrylamide); Anti-fungal; Amphotericin B; Nanoparticles

资金

  1. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (CAPES) [001 (PROEX 23038.000509/2020-82)]
  2. CNPq (Brazil) [408511/2016-8]
  3. INOMAT/CNPq [465452/2014-0]
  4. Central Analitica-UFC/CT-INFRA/MCTI-SISANO/Pro-Equipamentos CAPES

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Thermo-responsive copolymers were synthesized for loading galactomannan and antifungal drug amphotericin-B, showing good hemocompatibility and controlled release profile. The copolymer nanoparticles demonstrated effective antifungal activity with improved hemocompatibility compared to commercial amphotericin-B.
Thermo responsive copolymers were synthesized by radical polymerization of the N-isopropylacrylamide (NIPAm) onto galactomannan (GM) chain. All copolymers showed thermal responsiveness and a critical aggregation concentration (CAC) at 25 degrees C greater than at 50 degrees C. Below the lower critical solution temperature (LCST), copolymer nanoparticles presented sizes between 16 and 50 nm, whereas above LCST, they aggregate, presenting sizes in the range 145.8-194.0 nm, depending on NIPAm/GM molar ratio. Amphotericin-B (AmB) was encapsulated in the copolymer nanoparticles with encapsulation efficiency of 41.4 +/- 2.76% and 69.0 +/- 2.92% respectively for CP1 and CP2. In vitro AmB delivery from the CP1 nanoparticles was found to exhibit controlled release profile. Hemolysis assay was carried out using erythrocytes cells and samples of AmB loaded copolymer nanoparticles (CP1-AmB), unloaded copolymer nanoparticles (CP1) and commercial AmB were evaluated. Unloaded copolymer nanoparticles show hemocompatibility while the percentage of hemolysis of erythrocytes cells for CP1-AmB sample was 8.7 times lower than that observed for commercial AmB. CP1-AmB showed similar minimum inhibitory concentration (MIC) as commercial AmB, in four Candida albicans strains. As CP1-AmB nanoparticle show better hemocompatibility than commercial AmB, this thermo responsive copolymer shows potential as AmB nanocarrier device to be used in fungal infection.

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