Design, development, and evaluation of CDK-4/6 inhibitor loaded 4-carboxy phenyl boronic acid conjugated pH-sensitive chitosan lecithin nanoparticles in the management of breast cancer.

Our main aim to design and develop a novel 4-carboxy phenyl boronic acid (4-CPBA) conjugated Palbociclib (PALB) loaded pH-sensitive chitosan lipid nanoparticles (PPCL) to enhance the anti-cancer efficacy of the PALB in in-vitro cell line studies by loading into 4-CPBA conjugated chitosan lipid nanoparticles. 4-CPBA was conjugated to chitosan by carbodiimide chemistry and formation of conjugate was confirmed by 1HNMR, ATR-FTIR spectroscopic techniques. Ionic-gelation method was used for the fabrication of PPCL and particles size, PDI, zeta potential were found to be 226.5 ± 4.3 nm, 0.271 ± 0.014 and 5.03 ± 0.42 mV. Presence of pH-sensitive biological macromolecule i.e. chitosan in the carrier system provides pH-sensitivity to PPCL and sustainedly released the drug upto 144 h. The PPCL exhibited approximately 7.2, 6.6, and 5-fold reduction in IC50 values than PALB in MCF-7, MDA-MB-231 and 4T1 cells. Receptor blocking assay concluded that the fabricated nanoparticles were internalized into MCF-7 cells might be through sialic acid-mediated endocytosis. PPCL caused extensive mitochondrial depolarization, enhanced ROS generation, apoptosis (DAPI nuclear staining, acridine orange/ ethidium bromide dual staining), and reduced % cell migration than pure PALB. It was concluded that the hybrid lipid-polymer nanoparticles provides an optimistic approach for the treatment of breast cancer.

Thymoquinone-Loaded Essential Oil-Based Emulgel as an Armament for Anti-psoriatic Activity.

Essential oils consist of oxygenated structures of secondary metabolites of aromatic plants with anti-psoriatic activities. Tea tree oil (TTO) is an essential oil with good anti-microbial and anti-inflammatory properties, exhibiting reduced levels of IL-1, IL-8, and PGE 2. Thymoquinone (TMQ) is popular herb in traditional medicine with known therapeutic benefits in several diseases and ailments. The ternary phase diagram was prepared with the weight ratio of Smix (Tween® 80:Labrasol®): oil:water ratio for o/w emulsion preparation. The globule size was 16.54 ± 0.13 nm, and PDI around 0.22 ± 0.01 of the TTO-TMQ emulsion and found thermodynamically stable. The percentage drug content was found in the range of 98.97 ± 0.62 to 99.45 ± 0.17% with uniformity of the ThymoGel using Carbopol®. The extensive physicochemical properties were studied using different analytical techniques, and in vitro drug release was performed using Franz-diffusion apparatus. Anti-psoriatic activity of the formulations was studied using Imiquimod-induced psoriasis-like inflammation model in male Balb/c mice and parameters like PASI score, ear thickness, and spleen to body weight index were determined as well as histological staining, ELISA, skin compliance, and safety evaluation of TTO were performed. The combination of essential oils with TMQ shows synergistic activity and efficiently reduces the psoriasis disease condition.