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In silico ADMET profiling of Docetaxel and development of camel milk derived liposomes nanocarriers for sustained release of Docetaxel in triple negative breast cancer.
Kousar, Kousain; Shafiq, Shaheer; Sherazi, Syeda Tahira; Iqbal, Fareeha; Shareef, Usman; Kakar, Salik; Ahmad, Tahir.
Afiliación
  • Kousar K; Industrial Biotechnology, Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan. kousain777@outlook.com.
  • Shafiq S; Industrial Biotechnology, Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
  • Sherazi ST; Department of Gynecology, Unit 4, Sir Ganga Ram Hospital, Lahore, Pakistan.
  • Iqbal F; Industrial Biotechnology, Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
  • Shareef U; Shifa College of Pharmaceutical Sciences, Shifa Tameer E Millat University, Islamabad, Pakistan.
  • Kakar S; Industrial Biotechnology, Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
  • Ahmad T; Pak-Austria Fachhochschule: Institute of Applied Sciences and Technology, Khanpur Road, Mang Haripur, Khyber Pakhtunkhwa, Pakistan.
Sci Rep ; 14(1): 912, 2024 01 09.
Article en En | MEDLINE | ID: mdl-38195628
ABSTRACT
This study aimed at encapsulation of commonly administered, highly cytotoxic anticancer drug Docetaxel (DTX) in camel milk fat globule-derived liposomes for delivery in triple negative breast cancer cells. Prior to liposomal encapsulation of drug, in silico analysis of Docetaxel was done to predict off target binding associated toxicities in different organs. For this purpose, the ADMET Predictor (TM) Cloud version 10.4.0.5, 64-bit, was utilized to simulate Docetaxel's pharmacokinetic and physicochemical parameters. Freshly milked camel milk was bought from local market, from two breeds Brella and Marecha, in suburbs of Islamabad. After extraction of MFGM-derived liposomes from camel milk, docetaxel was loaded into liposomes by thin film hydration method. The physiochemical properties of liposomes were analyzed by SEM, FTIR and Zeta analysis. The results from SEM showed that empty liposomes (Lp-CM-ChT80) had spherical morphology while DTX loaded liposomes (Lp-CM-ChT80-DTX) exhibited rectangular shape, FTIR revealed the presence of characteristic functional groups which confirmed the successful encapsulation of DTX. Zeta analysis showed that Lp-CM-ChT80-DTX had size of 836.6 nm with PDI of 0.088 and zeta potential of - 18.7 mV. The encapsulation efficiency of Lp-CM-ChT80 turned out to be 25% while in vitro release assay showed slow release of DTX from liposomes as compared to pure DTX using dialysis membrane. The in vitro anticancer activity was analyzed by cell morphology analysis and MTT cytotoxicity assay using different concentrations 80 µg/ml, 120 µg/ml and 180 µg/ml of Lp-CM-ChT80-DTX on MDA-MB-231 cells. The results showed cytotoxic effects increased in time and dose dependent manner, marked by rounding, shrinkage and aggregation of cells. MTT cytotoxicity assay showed that empty liposomes Lp-CM-ChT80 did not have cytotoxic effect while Lp-CM-ChT80-DTX showed highest cytotoxic potential of 60.2% at 180 µg/ml. Stability analysis showed that liposomes were stable till 24 h in solution form at 4 °C.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antimitóticos / Neoplasias de la Mama Triple Negativas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Pakistán Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antimitóticos / Neoplasias de la Mama Triple Negativas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Pakistán Pais de publicación: Reino Unido