Quality by Design Approach in Liposomal Formulations: Robust Product Development.

Nanomedicine is an emerging field with continuous growth and differentiation. Liposomal formulations are a major platform in nanomedicine, with more than fifteen FDA-approved liposomal products in the market. However, as is the case for other types of nanoparticle-based delivery systems, liposomal formulations and manufacturing is intrinsically complex and associated with a set of dependent and independent variables, rendering experiential optimization a tedious process in general. Quality by design (QbD) is a powerful approach that can be applied in such complex systems to facilitate product development and ensure reproducible manufacturing processes, which are an essential pre-requisite for efficient and safe therapeutics. Input variables (related to materials, processes and experiment design) and the quality attributes for the final liposomal product should follow a systematic and planned experimental design to identify critical variables and optimal formulations/processes, where these elements are subjected to risk assessment. This review discusses the current practices that employ QbD in developing liposomal-based nano-pharmaceuticals.

Synthesis, Characterization, and Assessment of Anti-Cancer Potential of ZnO Nanoparticles in an In Vitro Model of Breast Cancer.

Advanced innovations for combating variants of aggressive breast cancer and overcoming drug resistance are desired. In cancer treatment, ZnO nanoparticles (NPs) have the capacity to specifically and compellingly activate apoptosis of cancer cells. There is also a pressing need to develop innovative anti-cancer therapeutics, and recent research suggests that ZnO nanoparticles hold great potential. Here, the in vitro chemical effectiveness of ZnO NPs has been tested. Zinc oxide (ZnO) nanoparticles were synthesized using Citrullus colocynthis (L.) Schrad by green methods approach. The generated ZnO was observed to have a hexagonal wurtzite crystal arrangement. The generated nanomaterials were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), UV-visible spectroscopy. The crystallinity of ZnO was reported to be in the range 50-60 nm. The NPs morphology showed a strong absorbance at 374 nm with an estimated gap band of 3.20 eV to 3.32 eV. Microscopy analysis proved the morphology and distribution of the generated nanoparticles to be around 50 nm, with the elemental studies showing the elemental composition of ZnO and further confirming the purity of ZnO NPs. The cytotoxic effect of ZnO NPs was evaluated against wild-type and doxorubicin-resistant MCF-7 and MDA-MB-231 breast cancer cell lines. The results showed the ability of ZnO NPs to inhibit the prefoliation of MCF-7 and MDA-MB-231 prefoliation through the induction of apoptosis without significant differences in both wild-type and resistance to doxorubicin.

Enhancing chemosensitivity of PANC1 pancreatic cancer cells to gemcitabine using ANGTPL4, Notch1 and NF-κß1 siRNAs.

Aim: siRNA can silence targeted genes with lesser toxicity than therapeutic drugs. Therefore, this study aims to investigate new approaches to treat pancreatic cancer (PC) using combinations of siRNA and gemcitabine. Methods: Three genes, ANGTPL4, Notch1 and NF-κß1, were silenced using siRNA, and their anti-proliferative effects were studied in combination with gemcitabine on pancreatic cancer cell line (PANC-1) using MTT viability assay. Results: Our results showed a significant reduction in PANC-1 cells growth upon treating cells with gemcitabine and single and combinations of siRNA sequences specific for ANGTPL4, Notch1 and NF-κß1 genes. Conclusion: Co-transfection of gemcitabine-treated PANC-1 cells with ANGPTL4, Notch1 and NF-κßsiRNAs enhances the chemosensitivity of PANC-1 cells to gemcitabine can be a promising therapeutic approach.

Pancreatic cancer (PC) is prominent with its aggressive behavior and metastatic properties, making it one of the leading causes of cancer-related deaths worldwide. PC is associated with poor prognosis and low survival rate, with 5 years survival rate of less than 9%. Moreover, only 20% of PC patients could undergo surgery, which makes investigating new therapeutic approaches to treat PC necessary. In the current study, the chemosensitivity of pancreatic cancer cells to gemcitabine has been enhanced using a single and combination of ANGTPL4, Notch1 and NF-κß1 siRNA.

Cinnamaldehyde-cucurbituril complex: investigation of loading efficiency and its role in enhancing cinnamaldehyde in vitro anti-tumor activity.

This study aimed to clarify the physico-chemical properties of cucurbit[7]uril (CB[7]) and cinnamaldehyde (Cinn) inclusion complexes (CB[7]-Cinn) and their resulting antitumor activity. CB[7]-Cinn inclusion complexes were prepared by a simple experimental approach and fully characterized for their stoichiometry, formation constant, particle size and morphology. Quantum chemical calculations were performed to elucidate the stable molecular structures of the inclusion complexes and their precursors and to investigate the probable stoichiometry and direction of interaction using three different DFT functionals at the 6-31G(d,p) basis set. The UV-vis spectrophotometric titrations as well as the Job plot, based on 1H NMR spectroscopy, suggested 1 : 1 and 1 : 2 stoichiometries of CB[7] : Cinn. The formation constants of the complexes were calculated using Benesi-Hildebrand equations and non-linear fittings. Moreover, the theoretical calculations confirmed the potential formation of 1 : 1 and 1 : 2 stoichiometries and clarify the orientation of binding from the Cinn phenyl moiety. The nanoparticles' TEM images showed a crystal-like spherical shape, smooth surface, with a small tendency to agglomerate. CB[7]-Cinn inclusion complexes were analyzed for their antitumor activity against MDA-MB-231 breast cancer and U-87 glioblastoma cell lines. The IC50 values were calculated after 72 hours of incubation with different concentrations of CB[7]-Cinn inclusion complexes and compared to free Cinn and free CB[7]. The IC50 values for free Cinn and CB[7]-Cinn inclusion complexes were 240.17 ± 32.46 µM and 260.47 ± 20.83 µM against U-87 cells and 85.93 ± 3.35 µM and 176.3 ± 7.79 µM against MDA-MB-231 cells, respectively, despite the enhanced aqueous solubility. No significant cytotoxicity was noticed for the free CB[7].

siRNA: Mechanism of action, challenges, and therapeutic approaches.

Owing to specific and compelling gene silencing, RNA interference (RNAi) is expected to become an essential approach in treating a variety of infectious, hemato-oncological, cardiovascular, and neurodegenerative conditions. The mechanism of action of small interfering RNA (siRNA) is based on post-transcriptional gene silencing. siRNA molecules are usually specific and efficient in the knockdown of disease-related genes. However, they are characterized by low cellular uptake and are susceptible to nuclease-mediated degradation. Therefore, siRNAs require a carrier for their protection and efficient delivery into target cells. The current review highlights the siRNA-based mechanism of action, challanges, and recent advances in clinical applications.