Oleanolic acid (OA), which is a natural pentacyclic terpenoid, has been identified for hepato-protective, nephron-protective and cardio-tonic properties. In contrast, doxorubicin (DOX) is a famous anti-cancer drug but its efficacy is a question mark because of its known cardio-toxicity. We developed a combined nanoliposomal formulation of DOX with OA, as adjuvant, to overwhelm toxic effects of DOX without compromising anticancer activity. The entrapment efficiency and the particle size were brought in limit by the reengineered ethanolic injection method (REIM), without further extrusion. The developed formulations were stable over the study period of two months. A modified HPLC method was employed for the analysis of OA (drug retention time, Tr = 12 ± 1 min). The recovery of OA against spiked plasma samples was more than 90%. MTT assay showed anti-apoptotic synergism against HepG2 cells at non-fixed ratio (combination index, CI < 1). A sustained in vivo drug release of experimental drugs was depicted over 24 h. Histopathological examination and laboratory findings indicated no visible sign of toxicity in the treated mice group against combined delivery. Hence, this combined nanoliposomal formulation was tagged as a safer therapy for the DOX based cancer treatments.

Respiratory diseases are leading causes of death and disability around the globe, with a diverse range of health problems. Treatment of respiratory diseases and infections has been verified to be thought-provoking because of the increasing incidence and mortality rate. Hydrogen sulfide (H₂S) is one of the recognized gaseous transmitters involved in an extensive range of cellular functions, and physiological and pathological processes in a variety of diseases, including respiratory diseases. Recently, the therapeutic potential of H₂S for respiratory diseases has been widely investigated. H₂S plays a vital therapeutic role in obstructive respiratory disease, pulmonary fibrosis, emphysema, pancreatic inflammatory/respiratory lung injury, pulmonary inflammation, bronchial asthma and bronchiectasis. Although the therapeutic role of H₂S has been extensively studied in various respiratory diseases, a concrete literature review will have an extraordinary impact on future therapeutics. This review provides a comprehensive overview of the effective role of H₂S in respiratory diseases. Besides, we also summarized H₂S production in the lung and its metabolism processes in respiratory diseases.

Hydrogen sulfide (H₂S), a gaseous signaling molecule, is associated with the development of various malignancies via modulating various cellular signaling cascades. Published research has established the fact that inhibition of endogenous H₂S production or exposure of H₂S donors is an effective approach against cancer progression. However, the effect of pharmacological inhibition of endogenous H₂S-producing enzymes (cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MPST)) on the growth of breast cancer (BC) remains unknown. In the present study, DL-propargylglycine (PAG, inhibitor of CSE), aminooxyacetic acid (AOAA, inhibitor of CBS), and L-aspartic acid (L-Asp, inhibitor of 3-MPST) were used to determine the role of endogenous H₂S in the growth of BC by in vitro and in vivo experiments. An in silico study was also performed to confirm the results. Corresponding to each enzyme in separate groups, we treated BC cells (MCF-7 and MDA-MB-231) with 10 mM of PAG, AOAA, and L-Asp for 24 h. Findings reveal that the combined dose (PAG + AOAA + L-Asp) group showed exclusive inhibitory effects on BC cells’ viability, proliferation, migration, and invasion compared to the control group. Further, treated cells exhibited increased apoptosis and a reduced level of phospho (p)-extracellular signal-regulated protein kinases such as p-AKT, p-PI3K, and p-mTOR. Moreover, the combined group exhibited potent inhibitory effects on the growth of BC xenograft tumors in nude mice, without obvious toxicity. The molecular docking results were consistent with the wet lab experiments and enhanced the reliability of the drugs. In conclusion, our results demonstrate that the inhibition of endogenous H₂S production can significantly inhibit the growth of human breast cancer cells via the AKT/PI3K/mTOR pathway and suggest that endogenous H₂S may act as a promising therapeutic target in human BC cells. Our study also empowers the rationale to design novel H₂S-based anti-tumor drugs to cure BC.

Conventional eye drops show low bioavailability (below 20%) due to the eye's inherent tissue barriers and unique microenvironment. Recent advancements in pharmaceutical nanotechnology have explored various nanoparticle systems, such as micelles, liposomes, and nanoemulsions, to enhance corneal permeation and prolong drug retention. In this study, we propose a twin nanoparticulate system, combining the advantages of two nanoparticles to improve drug targeting and therapeutic efficacy. A dexamethasone-loaded liposome–microemulsion (LME) twin nanoparticulate system was developed using high-pressure homogenization and successfully scaled up. Both liposomes and microemulsions were of similar size (∼60 nm) and displayed uniform distribution (polydispersity index < 0.2) upon combination. The final formulation was hypo-osmolar (osmolality < 100 mOsm per Kg), making it ideal for dry eye relief. Drug release was extended for up to 8 h, following a non-Fickian diffusion pattern. The LME formulation, tested under different conditions (2–8 °C and 25 °C with 60% relative humidity), was found to be stable for 6 months. It showed no cytotoxicity in human corneal epithelial cells up to 10 μM drug concentration. Fluorescence microscopy revealed rapid nanoparticle uptake by cells within 5 minutes. Human corneal epithelial cells showed a marked reduction in inflammatory biomarkers (IL-6, IL-8, and TNF-α) after drug-loaded LME treatments, compared to the control. Corneal tissue imaging confirmed prolonged retention of nanoparticles within the tissue. A whole eye ex vivo permeation study demonstrated higher drug concentrations in the aqueous humour of LME drug-treated rabbit eyes compared to a reference product. This twin nanoparticulate system, loaded with dexamethasone, offers a promising next-generation treatment for dry eye disease (DED).