QbD Enabled Azacitidine Loaded Liposomal Nanoformulation and Its In Vitro Evaluation

Abstract

Azacitidine (AZA), an inhibitor of DNA methyltransferase, is a commonly recognized drug used in clinical treatment for myelodysplastic syndrome and breast cancer. Due to higher aqueous solubility and negative log P of AZA causes poor cancer cell permeation and controlled release. The objective of the present study was to formulate and optimize AZA-loaded liposome (AZA-LIPO) for breast cancer chemotherapy by using Box Behnken design (BBD) and in vitro evaluation using MCF-7 cells. AZA-LIPO were prepared using a thin film hydration technique and characterization study was performed by using FTIR and DSC. The prepared formulations were optimized using BBD and the optimized formulation was further subjected for particle size, surface charges, polydispersity index (PDI), drug loading, entrapment efficiency, TEM, XRD, in-vitro drug release and hemolytic toxicity. The mean particle size of optimized AZA-LIPO was 127 nm. Entrapment efficiency and drug loading of AZA-LIPO was found to be 85.2% ± 0.5 and 6.82 ± 1.6%, respectively. Further, in vitro drug release study showed preliminary burst release in 2 h followed by a sustained release for 36 h in phosphate buffer at different pH (4.0, 5.5, and 7.4) as compared to free drug. Drug release was found to be pH dependent, as the pH was increased, the drug release rate was found to be low. Time-dependent cell viability assay exhibited significant higher cell viability and higher internalization than free AZA in MCF-7 cells. AZA-LIPO were more effective than the free AZA in reducing Bcl2 expression, while increasing pro-apoptotic Bax and caspase-3 activity. The result showed that the formulated biocompatible AZA-LIPO nano-formulations may be used as an efficient anti-cancer drug delivery system for the treatment of breast cancer after establishing preclinical and clinical studies.

Enhanced Codelivery of Gefitinib and Azacitidine for Treatment of Metastatic-Resistant Lung Cancer Using Biodegradable Lipid Nanoparticles

“…The PXRD spectrum of GEF displayed two predominant peaks at 38.1 and 44.3 • C, in addition to moderate peaks at 19.4 and 77.5 • C, which is consistent with the reported spectrum by Alshehri et al [41]. The spectrum shows that AZT had multiple peaks between 12.2 and 29.3 • C, with an additional peak at 38.0 • C, in agreement with previously reported studies by Kesharwani et al [29].…”

“…The dialysis bag method was utilized to evaluate GEF and AZT release from the prepared formulations [23,29]. About 0.5 mL from each formulation was diluted (1:4) and placed within a dialysis membrane bag (molecular-weight cut-off: 12-14 kDa).…”

The effect of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) Addition on the physical characteristics of β-ionone liposomes

“…Several identical peaks in DOTAP and β-ionone were not visible in the spectra of the liposomes loaded β-ionone with DOTAP addition, indicating that there could be physical interaction 39 . Meanwhile, the spectra shown for each liposome formula did not indicate a significant difference in the intensity of the absorption bands.…”

Optical Imaging of Epigenetic Modifications in Cancer: A Systematic Review

“…Using single-molecule fluorescence, the vast majority of these nano-micelles could be detected in cancer cells. Moreover, experimental data clearly demonstrated the great potential of these nano-micelles in clinical cancer practice (Kesharwani et al 2021). Thus, the optical molecular imaging of epigenetics modification strategy may help develop structure-based drugs for cancer precision treatment.…”