Quality by design approach-based fabrication and evaluation of self-nanoemulsifying drug delivery system for improved delivery of venetoclax.

Autor: Rajana, Naveen, Chary, Padakanti Sandeep, Pooja, Yeruva Sri, Bhavana, Valamla, Singh, Hoshiyar, Guru, Santosh Kumar, Singh, Shashi Bala, Mehra, Neelesh Kumar
Zdroj: Drug Delivery & Translational Research; May2024, Vol. 14 Issue 5, p1277-1300, 24p
Abstrakt: Breast cancer is reported as one of the most prevalent non-cutaneous malignancies in women. Venetoclax (VEN) is an approved BCl-2 inhibitor for the treatment of chronic myeloid leukemia with very limited oral bioavailability and exhibits an enormous impact on breast cancer. In the current investigation, venetoclax-loaded self-nanoemulsifying drug delivery systems (VEN-SNEDDS) were designed and fabricated to improve the aqueous solubility, permeability, and anticancer efficacy of VEN. Various surface-active parameters of the reconstituted SNEDDS were determined to scrutinize the performance of the selected surfactant mixture. Central composite design (CCD) was used to optimize the VEN-SNEDDS. The globule size of reconstituted VEN-SNEDDS was 71.3 ± 2.8 nm with a polydispersity index of 0.113 ± 0.01. VEN-SNEDDS displayed approximately 3–4 fold, 6–7 fold, and 5–6 fold reduced IC50 as compared to free VEN in MDA-MB-231, MCF-7, and T47 D cells, respectively. VEN-SNEDDS showed greater cellular uptake, apoptosis, reactive oxygen species generation, and higher BAX/BCL2 ratio with decreased caspase 3 and 8 and BCL-2 levels in the MDA-MB-231 cells compared to pure VEN. VEN-SNEDDS exhibited approximately fivefold enhancement in Cmax and an improved oral bioavailability compared to VEN suspension in in vivo pharmacokinetic studies. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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