Molecular inclusion complex with gama-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) is a semi-synthetic derivative of 10-deacetyl-baccatin III, a non-cytotoxic compound extracted from yew leaves (Taxus baccata L). DTX use for the
treatment of anthracycline-refractory metastatic breast cancer (1996) was then
expanded for skin, lung, prostate, gastric, head/neck and other neoplasias. However,
as a class IV BCS drug, the clinical application of docetaxel is limited by its low water
solubility (5 mg/L or 6 µM), intestinal permeability and fast elimination. Also, the use
of commercially available DTX formulations is associated to adverse effects such as
neutropenia, hypersensitivity reactions, peripheral neuropathy, musculoskeletal
toxicity and nasolacrimal duct stenosis. To overcome such adverse effects and
increase DTX anticancer potential we investigated the inclusion complexation of DTX
with cyclodextrins (CD). CD are known to accommodate molecules of proper size and
polarity into their macrocyclic ring, forming host-guest inclusion complexes.
Complexation in CD may improve the aqueous solubility, increase the stability and
prolong the release kinetics of the guest molecule. In here we report results on the
characterization of a DTX:gama-cyclodextrin complex. The DTX:gCD inclusion
complex was prepared by the co-solubilization method, lyophilized, and characterized
regarding the equilibrium time (5 h) and stoichiometry of complexation (1:2). As
expected, complexation significantly increased (20-fold) the aqueous solubility of DTX
and biophysical techniques (DSC and X-ray) provided evidence of DTX:gCD complex
formation. In vitro release kinetics tests were conducted to compare the release of
DTX from the complex with that of the commercial DTX formulation (Taxotere®).
Finally, cytotoxic effects against breast cancer cells (4T1) and normal fibroblasts (NIH-3T3) had been evaluated. Both DTX:g-CD and Taxotere® caused significant reduction
in the cell viability of breast cancer cells, even at the lowest concentration tested (5x10-
11M). Interestingly, DTX:g-CD complex was found to be less toxic to NIH-3T3 non-tumor cells than Taxotere® (cell viability was reduced to 48.5 ± 2.4% with DTX:g-CD
and to 20.2 ± 0.8% with Taxotere® at the concentration of 5mM). These preliminary
results suggest that DTX:gCD may represent a new drug delivery system, capable of
reducing the toxicity and enhancing the effectiveness of DTX in cancer treatment.
Como referenciar
SAMPAIO, THIAGO S.; MENDONCA, NATALIA S.; CARVALHO, FABIOLA V.; YOKAICHIYA, FABIANO; FRANCO, MARGARETH K.K.D.; PAULA, ENEIDA de. Molecular inclusion complex with gama-cyclodextrin: an alternative pharmaceutical form to deliver docetaxel. 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/123456789/49145. 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.