In silico ADMET profiling of Docetaxel and development of camel milk derived liposomes nanocarriers for sustained release of Docetaxel in triple negative breast cancer.

This study aimed at encapsulation of commonly administered, highly cytotoxic anticancer drug Docetaxel (DTX) in camel milk fat globule-derived liposomes for delivery in triple negative breast cancer cells. Prior to liposomal encapsulation of drug, in silico analysis of Docetaxel was done to predict off target binding associated toxicities in different organs. For this purpose, the ADMET Predictor (TM) Cloud version 10.4.0.5, 64-bit, was utilized to simulate Docetaxel's pharmacokinetic and physicochemical parameters. Freshly milked camel milk was bought from local market, from two breeds Brella and Marecha, in suburbs of Islamabad. After extraction of MFGM-derived liposomes from camel milk, docetaxel was loaded into liposomes by thin film hydration method. The physiochemical properties of liposomes were analyzed by SEM, FTIR and Zeta analysis. The results from SEM showed that empty liposomes (Lp-CM-ChT80) had spherical morphology while DTX loaded liposomes (Lp-CM-ChT80-DTX) exhibited rectangular shape, FTIR revealed the presence of characteristic functional groups which confirmed the successful encapsulation of DTX. Zeta analysis showed that Lp-CM-ChT80-DTX had size of 836.6 nm with PDI of 0.088 and zeta potential of - 18.7 mV. The encapsulation efficiency of Lp-CM-ChT80 turned out to be 25% while in vitro release assay showed slow release of DTX from liposomes as compared to pure DTX using dialysis membrane. The in vitro anticancer activity was analyzed by cell morphology analysis and MTT cytotoxicity assay using different concentrations 80 µg/ml, 120 µg/ml and 180 µg/ml of Lp-CM-ChT80-DTX on MDA-MB-231 cells. The results showed cytotoxic effects increased in time and dose dependent manner, marked by rounding, shrinkage and aggregation of cells. MTT cytotoxicity assay showed that empty liposomes Lp-CM-ChT80 did not have cytotoxic effect while Lp-CM-ChT80-DTX showed highest cytotoxic potential of 60.2% at 180 µg/ml. Stability analysis showed that liposomes were stable till 24 h in solution form at 4 °C.

A comprehensive review of discovery and development of drugs discovered from 2020-2022.

To fully evaluate and define the new drug molecule for its pharmacological characteristics and toxicity profile, pre-clinical and clinical studies are conducted as part of the drug research and development process. The average time required for all drug development processes to finish various regulatory evaluations ranges from 11.4 to 13.5 years, and the expense of drug development is rising quickly. The development in the discovery of newer novel treatments is, however, largely due to the growing need for new medications. Methods to identify Hits and discovery of lead compounds along with pre-clinical studies have advanced, and one example is the introduction of computer-aided drug design (CADD), which has greatly shortened the time needed for the drug to go through the drug discovery phases. The pharmaceutical industry will hopefully be able to address the present and future issues and will continue to produce novel molecular entities (NMEs) to satisfy the expanding unmet medical requirements of the patients as the success rate of the drug development processes is increasing. Several heterocyclic moieties have been developed and tested against many targets and proved to be very effective. In-depth discussion of the drug design approaches of newly found drugs from 2020 to 2022, including their pharmacokinetic and pharmacodynamic profiles and in-vitro and in-vivo assessments, is the main goal of this review. Considering the many stages these drugs are going through in their clinical trials, this investigation is especially pertinent. It should be noted that synthetic strategies are not discussed in this review; instead, they will be in a future publication.

Formulation for the Targeted Delivery of a Vaccine Strain of Oncolytic Measles Virus (OMV) in Hyaluronic Acid Coated Thiolated Chitosan as a Green Nanoformulation for the Treatment of Prostate Cancer: A Viro-Immunotherapeutic Approach.

Background: Oncolytic viruses are reported as dynamite against cancer treatment nowadays. Methodology: In the present work, a live attenuated oral measles vaccine (OMV) strain was used to formulate a polymeric surface-functionalized ligand-based nanoformulation (NF). OMV (half dose: not less than 500 TCID units; 0.25 mL) was encapsulated in thiolated chitosan and outermost coating with hyaluronic acid by ionic gelation method characterizing parameters was performed. Results and Discussion: CD44 high expression was confirmed in prostatic adenocarcinoma (PRAD) by GEPIA which extracted data of normal and cancer tissue from GTEx and TCGA. Bioinformatics tools confirmed the viral hemagglutinin capsid protein interaction with human Caspase-I, NLRP3, and TNF-α and viral fusion protein interaction with COX-II and Caspase-I after successful delivery of MV encapsulated in NFs due to high affinity of hyaluronic acid with CD44 on the surface of prostate cancer cells. Particle size = 275.6 mm, PDI = 0.372, and ±11.5 zeta potential were shown by zeta analysis, while the thiolated group in NFs was confirmed by FTIR and Raman analysis. SEM and XRD showed a spherical smooth surface and crystalline nature, respectively, while TEM confirmed virus encapsulation within nanoparticles, which makes it very useful in targeted virus delivery systems. The virus was released from NFs in a sustained but continuous release pattern till 48 h. The encapsulated virus titer was calculated as 2.34×107 TCID50/mL units, which showed syncytia formation on post-day infection 7. Multiplicities of infection 0.1, 0.5, 1, 3, 5, 10, 15, and 20 of HA-coated OMV-loaded NFs as compared to MV vaccine on PC3 was inoculated with IC50 of 5.1 and 3.52, respectively, and growth inhibition was seen after 72 h via MTT assay which showed apoptotic cancer cell death. Conclusion: Active targeted, efficacious, and sustained delivery of formulated oncolytic MV is a potent moiety in cancer treatment at lower doses with safe potential for normal prostate cells.

A Review on Therapeutic Potential of Natural Phytocompounds for Stroke.

Stroke is a serious condition that results from an occlusion of blood vessels that leads to brain damage. Globally, it is the second highest cause of death, and deaths from strokes are higher in older people than in the young. There is a higher rate of cases in urban areas compared to rural due to lifestyle, food, and pollution. There is no effective single medicine for the treatment of stroke due to the multiple causes of strokes. Thrombolytic agents, such as alteplase, are the main treatment for thrombolysis, while multiple types of surgeries, such ascraniotomy, thrombectomy, carotid endarterectomy, and hydrocephalus, can be performed for various forms of stroke. In this review, we discuss some promising phytocompounds, such as flavone C-glycoside (apigenin-8-C-ß-D-glucopyranoside), eriodictyol, rosamirinic acid, 6″-O-succinylapigenin, and allicin, that show effectiveness against stroke. Future study paths are given, as well as suggestions for expanding the use of medicinal plants and their formulations for stroke prevention.