QbD-based design and characterization of mucoadhesive microspheres of quetiapine fumarate with improved oral bioavailability and brain biodistribution potential

The present work aims to discuss on Quality by Design based development and characterization of the sustained release mucoadhesive microspheres of quetiapine fumarate. The microspheres were prepared by non-aqueous solvent evaporation process. Factor screening study was carried out using fractional factorial design for identifying the influential factors. Systematic optimization of microspheres was accomplished by Box-Behnken design and characterized for particle size, entrapment efficiency, in vitro drug release and ex vivo mucoadhesion strength, which indicated that microspheres were consequence to be spherical and free flowing in nature. The microspheres exhibited high drug entrapment efficiency and in vitro drug release in a sustained manner, which was considered to be dependent on the concentration of rate controlling polymers. Ex vivo wash-off test on microspheres indicated good mucoadhesive property on excised goat intestinal mucosa. Out of all the accepted formulation, F6 was preferred as the optimized formulation. In vivo pharmacokinetic and brain biodistribution study revealed significant increase in the levels of drug in blood plasma and brain homogenates from the optimized formulation vis-à-vis the pure drug suspension. Overall, current study corroborated significant improvement in the biopharmaceutical attributes of quetiapine fumarate from mucoadhesive microspheres, which can be effectively used for management of depression and schizophrenia. Keywords: Quality by Design, DoE, Sustained release, Mucoadhesion, Depressio

ABHD11-AS1: An Emerging Long Non-Coding RNA (lncRNA) with Clinical Significance in Human Malignancies

The aberrant expression of lncRNAs has been linked to the development and progression of different cancers. One such lncRNA is ABHD11 antisense RNA 1 (ABHD11-AS1), which has recently gained attention for its significant role in human malignancies. ABHD11-AS1 is highly expressed in gastric, lung, breast, colorectal, thyroid, pancreas, ovary, endometrium, cervix, and bladder cancers. Several reports highlighted the clinical significance of ABHD11-AS1 in prognosis, diagnosis, prediction of cancer progression stage, and treatment response. Significantly, the levels of ABHD11-AS1 in gastric juice had been exhibited as a clinical biomarker for the assessment of gastric cancer, while its serum levels have prognostic potential in thyroid cancers. The ABHD11-AS1 has been reported to exert oncogenic effects by sponging different microRNAs (miRNAs), altering signaling pathways such as PI3K/Akt, epigenetic mechanisms, and N6-methyladenosine (m6A) RNA modification. In contrast, the mouse homolog of AHD11-AS1 (Abhd11os) overexpression had exhibited neuroprotective effects against mutant huntingtin-induced toxicity. Considering the emerging research reports, the authors attempted in this first review on ABHD11-AS1 to summarize and highlight its oncogenic potential and clinical significance in different human cancers. Lastly, we underlined the necessity for future mechanistic studies to unravel the role of ABHD11-AS1 in tumor development, prognosis, progression, and targeted therapeutic approaches