Plants and their derived molecules have been traditionally used to manage numerous pathological complications, including male erectile dysfunction (ED). Mimosa pudica Linn. commonly referred to as the touch-me-not plant, and its extract are important sources of new lead molecules in drug discovery research. The main goal of this study was to predict highly effective molecules from M. pudica Linn. for reaching and maintaining penile erection before and during sexual intercourse through in silico molecular docking and dynamics simulation tools. A total of 28 bioactive molecules were identified from this target plant through public repositories, and their chemical structures were drawn using Chemsketch software. Graph theoretical network principles were applied to identify the ideal target (phosphodiesterase type 5) and rebuild the network to visualize the responsible signaling genes, proteins, and enzymes. The 28 identified bioactive molecules were docked against the phosphodiesterase type 5 (PDE5) enzyme and compared with the standard PDE5 inhibitor (sildenafil). Pharmacokinetics (ADME), toxicity, and several physicochemical properties of bioactive molecules were assessed to confirm their drug-likeness property. Molecular dynamics (MD) simulation modeling was performed to investigate the stability of PDE5–ligand complexes. Four bioactive molecules (Bufadienolide (−12.30 kcal mol⁻¹), Stigmasterol (−11.40 kcal mol⁻¹), Isovitexin (−11.20 kcal mol⁻¹), and Apigetrin (−11.20 kcal mol⁻¹)) showed the top binding affinities with the PDE5 enzyme, much more powerful than the standard PDE5 inhibitor (−9.80 kcal mol⁻¹). The four top binding bioactive molecules were further validated for a stable binding affinity with the PDE5 enzyme and conformation during the MD simulation period as compared to the apoprotein and standard PDE5 inhibitor complexes. Further, the four top binding bioactive molecules demonstrated significant drug-likeness characteristics with lower toxicity profiles. According to the findings, the four top binding molecules may be used as potent and safe PDE5 inhibitors and could potentially be used in the treatment of ED.

Lower doses of capsaicin (8-methyl- N -vanillyl-6-nonenamide) have the potential to serve as an anticancer drug, however, due to its pungency, irritant effect, poor water solubility and high distribution volume often linked to various off-target effects, its therapeutic use is limited. This study aimed to determine the biodistribution and anticancer efficacy of capsaicin loaded solid lipid nanoparticles (SLNs) in human hepatocellular carcinoma in vitro . In this study, SLNs of stearic acid loaded with capsaicin was formulated by the solvent evaporation-emulsification technique and were instantly characterized for their encapsulation efficiency, morphology, loading capacity, stability, particle size, charge and in vitro drug release profile. Synthesized SLNs were predominantly spherical, 80 nm diameter particles that proved to be biocompatible with good stability in aqueous conditions. In vivo biodistribution studies of the formulated SLNs showed that 48 h after injection in the lateral tail vein, up to 15% of the cells in the liver, 1.04% of the cells in the spleen, 3.05% of the cells in the kidneys, 3.76% of the cells in the heart, 1.31% of the cells in the lungs and 0% of the cells in the brain of rats were determined. Molecular docking studies against the identified targets in HepG2 cells showed that the capsaicin is able to bind Abelson tyrosine-protein kinase, c-Src kinase, p38 MAP kinase and VEGF-receptor. Molecular dynamic simulation showed that capsaicin-VEGF receptor complex is highly stable at 50 nano seconds. The IC ₅₀ of capsaicin loaded SLNs in HepG2 cells in vitro was 21.36 μ g × ml ⁻¹ . These findings suggest that capsaicin loaded SLNs are stable in circulation for a period up to 3 d, providing a controlled release of loaded capsaicin and enhanced anticancer activity.

Cancer immunotherapy is an innovative way of treating cancer by stimulating individual cells to overcome cancer. Widespread biomedical studies were carried out with the aim of exploring immunotherapy cancer therapeutics, and this review spotlights some mechanisms in which it was developed, namely immune checkpoint inhibitors (E.G PD-1/PD-L1, CTLA-4), adoptive cell therapy (e.g., CAR T-cell therapy), and cancer vaccines. Although it has shown clinical benefit in a number of cancer types, including melanoma and non-small-cell lung cancer, several challenges have dampened enthusiasm for this approach, from the differing patient response rates to toxicities. Nanotechnology in drug delivery systems must play a role in overcoming the same. Nanotechnology enables increased specificity and controlled drug release, improved solubility and bioavailability, can treat the tumor specifically, and localized drug delivery at the disease site decreases systemic toxicity. The review also features advances in the construction of lipid-based, polymeric, and inorganic nanoparticles that improve drug stability and allow the delivery of cotherapeutic agents. Nanotechnology-based delivery systems can be used alone or in combination with immunotherapy to assist in improving the immune response, gaining access to the tumor microenvironment, and overcoming biological barriers. Thus, the nano-DDS were both safe and effective in preclinical studies, and ongoing clinical trials have shown that they are capable of increasing the therapeutic index of anticancer drugs. Lastly, the review also discusses current challenges and regulatory issues in advancing these technologies and highlights the importance of further research to devise appropriate methodology for efficient functionalization of nanotechnology for individualized cancer solutions in cancer treatment.

Targeted drug delivery systems are a promising field of research. Nano-engineered material-mediated drug delivery possesses remarkable potential for the treatment of various malignancies. Here, folic acid (FA)-conjugated bovine serum albumin (BSA) nanoparticles (NPs) were used to encapsulate myricetin (Myr). Subsequently, the delivery of Myr via naturally overexpressed folate receptor (FR) to FR-positive breast cancer cells was studied. Myr-loaded BSA NPs were assembled by modified desolvation cross-linking technique. An FA-conjugated carrier, N-hydroxysuccinimide (NHS)-FA ester, was successfully synthesized. Its functional and structural characteristics were confirmed by ultraviolet, Fourier-transform infrared, and proton nuclear magnetic resonance spectroscopy. Biocompatible FA-conjugated, Myr-loaded BSA NPs (FA-Myr-BSA NPs) were successfully formulated using a carbonate/bicarbonate buffer. Their morphology, size, shape, physiological stability, and drug release kinetics were studied. Molecular docking studies revealed that FA-Myr-BSA NPs readily bound non-covalently to folate receptors and facilitated active drug endocytosis. FA-Myr-BSA NPs could trigger fast release of Myr in an acidic medium (pH 5.4), and showed high biocompatibility in a physiological medium. FA-Myr-BSA NPs effectively decreased the viability of MCF-7 cells after 24 h with 72.45 μ g ml ⁻¹ IC ₅₀ value. In addition, FA-Myr-BSA NPs enhanced the uptake of Myr in MCF-7 cells. After incubation, a typical apoptotic morphology of condensed nuclei and distorted membrane bodies was observed. The NPs also targeted mitochondria of MCF-7 cells, significantly increasing reactive oxygen species release and contributing to the loss of mitochondrial membrane integrity. The observed results confirm that the newly developed FA-Myr-BSA NPs can serve as a potential carrier for Myr to increase the anticancer activity of this chemotherapeutic.