Complexation of the chemotherapeutic docetaxel with hydroxypropyl-γ-cyclodextrin
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2024
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ANNUAL MEETING OF THE BRAZILIAN BIOPHYSICAL SOCIETY, 48th
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Resumo
Docetaxel (DTX) a chemotherapy drug of the taxane class is recognized as an
essential medicine by the World Health Organization (WHO) for treating various
cancers, including breast cancer. Classified under class IV of the biopharmaceutical
classification system, DTX has low water solubility (6 μM) and limited bioavailability.
Commercial DTX formulations employ a non-ionic surfactant (polysorbate 80) and
ethanol to enhance solubility which exacerbates the side effects of chemotherapy.
Forming inclusion complexes with cyclodextrins (CDs) presents a promising strategy
to improve drug solubility. CDs are cyclic oligosaccharides derived from starch
degradation by the bacterial enzyme cyclodextrin glucosyltransferase. α-, β- and γ-cyclodextrins are the most abundant natural CDs, but their applications are limited due
to poor drug-binding capacity and toxicity concerns, especially in parenteral
administration. To address these issues, chemically modified CDs such as
hydroxypropyl-γ-CD (HP-γ-CD) have been developed. In this study, a DTX:HP-γ-CD
inclusion complex was prepared by the co-solubilization method followed by freeze-drying, in a 1:2 stoichiometric ratio and an equilibration time of 6 hours.
Characterization techniques such as scanning electron microscopy (SEM) and X-ray
diffraction were employed. The complexation markedly increased the aqueous
solubility of DTX by up to 25 times (150 μM). SEM micrographs indicated that DTX
loses its crystalline structure upon complexation, resulting in an amorphous
arrangement similar to HP-γ-CD. X-ray diffraction confirmed the loss of DTX's
crystalline pattern in the inclusion complex, a phenomenon not observed in the physical
mixture of excipients. The dimensions of the DTXHP-γ-CD complex (D=18.09, d= 10.13
and h= 8.07 angstroms) compared to pure HP-γ-CD (D=17.57, d= 10.56 and h= 8.96
angstroms) suggest that docetaxel slightly enlarges the size of the external ring and
internal cavities (D and d, respectively) of HP-γ-CD and decreases the height of its
cone (h); additionally, there was a decrease in peak intensity from the physical mixture to the complex. These results provide compelling evidence of the complexation
between DTX and modified γ-cyclodextrin. This complex holds the potential to become
a new formulation with reduced side effects and enhanced therapeutic efficacy against
cancer.
Como referenciar
MENDONCA, NATALIA S.; SAMPAIO, THIAGO S.; CARVALHO, FABIOLA V.; YOKAICHIYA, FABIANO; FRANCO, MARGARETH K.K.D.; PAULA, ENEIDA de; SOUZA, TATIANE P. de. Complexation of the chemotherapeutic docetaxel with hydroxypropyl-γ-cyclodextrin: a strategy to increase drug's solubility. In: ANNUAL MEETING OF THE BRAZILIAN BIOPHYSICAL SOCIETY, 48th, October, 2-5, 2024, São Paulo, SP. Abstract... Campinas, SP: Galoá, 2024. Disponível em: https://repositorio.ipen.br/handle/123456789/49143. Acesso em: 20 Jan 2026.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.