1. Enhanced oral bioavailability and in vitro evaluation of cannabidiol camel milk-derived exosome formulation in resistant MDA-MB-231 and MDA-MB-468 breast cancer cells.
- Author
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Aare M, Bagde A, Nathani A, Rishi AK, and Singh M
- Subjects
- Animals, Humans, Cell Line, Tumor, Female, Dogs, Madin Darby Canine Kidney Cells, Administration, Oral, Doxorubicin pharmacokinetics, Doxorubicin administration & dosage, Doxorubicin pharmacology, Doxorubicin chemistry, Drug Liberation, Cell Survival drug effects, Rats, Sprague-Dawley, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents administration & dosage, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Exosomes, Biological Availability, Milk chemistry, Cannabidiol pharmacokinetics, Cannabidiol chemistry, Cannabidiol administration & dosage, Cannabidiol pharmacology, Breast Neoplasms drug therapy, Drug Resistance, Neoplasm drug effects, Camelus
- Abstract
The potential of camel milk-derived exosomes (CMDE) to enhance the bioavailability of Cannabidiol (CBD) was investigated. CBD-CMDE formulation was prepared using an established procedure and its particle size was 138.4 ± 4.37 nm, and CBD entrapment efficiency of 56.56 ± 4.26 %. In-vitro release studies showed release of 78.27 ± 5.37 % and 46.42 ± 4.75 % CBD from CMDE and control CBD formulation respectively in pH 6.8 at 24 hr. The apparent permeability (Papp) of CBD-CMDE was found to be enhanced by 3.95-fold with Papp of 22.9*10
-6 ± 0.34 cm/sec as compared to control CBD formulation with Papp of 5.8*10-6 ± 0.65 cm/sec in MDCK cells. CBD-CMDE was found to be more potent than CBD in 2D cytotoxicity assay with IC50 values of 3.6 ± 0.54 µM, 3.88 ± 0.54 µM and 7.53 ± 0.59 µM, 7.53 ± 0.59 µM against Doxorubicin (DOX) resistant MDA-MB-231 and Rapamycin (RM) resistant MDA-MB-468 breast cancer cells respectively. Moreover, 3D spheroids assay results demonstrated CBD-CMDE with IC50 values of 14 ± 0.85 µM, 15 ± 0.07 µM as compared to CBD alone with IC50 values of 25 ± 0.93 µM, 34.7 ± 0.08 µM in MDA-MB-231 DOX RT cells and MDA-MB-468 RM RT cells respectively. In-vivo PK studies showed enhanced bioavailability of CBD from CBD-exosomes with AUC(0-24h) of 1350.56 ± 187.50 h.ng/mL as compared to CBD control formulation with AUC(0-24h) of 351.95 ± 39.10 h.ng/mL with a single oral dose of 12 mg/kg. The data indicate that CMDE significantly improved the oral bioavailability of CBD. Overall, CMDE can be used to enhance the oral absorption of poorly bioavailable APIs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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