Human plasma derived exosomes: Impact of active and passive drug loading approaches on drug delivery.

The aim of the current study was to explore the potential of human plasma-derived exosomes as versatile carriers for drug delivery by employing various active and passive loading methods. Exosomes were isolated from human plasma using differential centrifugation and ultrafiltration method. Drug loading was achieved by employing sonication and freeze thaw methods, facilitating effective drug encapsulation within exosomes for delivery. Each approach was examined for its effectiveness, loading efficiency and ability to preserve membrane stability. Methotrexate (MTX), a weak acid model drug was loaded at a concentration of 2.2 µM to exosomes underwent characterization using various techniques such as particle size analysis, transmission electron microscopy and drug loading capacity. Human plasma derived exosomes showed a mean size of 162.15 ± 28.21 nm and zeta potential of -30.6 ± 0.71 mV. These exosomes were successfully loaded with MTX demonstrated a better drug encapsulation of 64.538 ± 1.54 % by freeze thaw method in comparison 55.515 ± 1.907 % by sonication. In-vitro drug release displayed 60 % loaded drug released within 72 h by freeze thaw method that was significantly different from that by sonication method i.e., 99 % within 72 h (p value 0.0045). Moreover, cell viability of exosomes loaded by freeze thaw method was significantly higher than that by sonication method (p value 0.0091) suggested that there was membrane disruption by sonication method. In conclusion, this study offers valuable insights into the potential of human plasma-derived exosomes loaded by freeze thaw method suggest as a promising carrier for improved drug loading and maintenance of exosomal membrane integrity.

Countenance and implication of Β-sitosterol, Β-amyrin and epiafzelechin in nickel exposed Rat: in-silico and in-vivo approach.

The detrimental impact of reactive oxygen species on D.N.A. repair processes is one of the contributing factors to colon cancer. The idea that oxidative stress may be a significant etiological element for carcinogenesis is currently receiving more and more support. The goal of the current study is to evaluate the anti-inflammatory and anticancer activity of three powerful phytocompounds-sitosterol, amyrin, and epiafzelechin-alone and in various therapeutic combinations against colon cancer to identify the critical mechanisms that mitigate nickel's carcinogenic effect. To evaluate the ligand-protein interaction of four selected components against Vascular endothelial growth factor (VEGF), Matrix metalloproteinase-9 (MMP9) inhibitor and Interleukin-10 (IL-10) molecular docking approach was applied using PyRx bioinformatics tool. For in vivo analysis, hundred albino rats were included, divided into ten groups, each containing ten rats of weight 160-200 g. All the groups were injected with 1 ml/kg nickel intraperitoneally per week for three months, excluding the negative control group. Three of the ten groups were treated with ß-sitosterol (100 mg/kg b wt), ß-amyrin (100 mg/kg b wt), and epiafzelechin (200 mg/kg b wt), respectively, for one month. The later four groups were fed with combinatorial treatments of the three phyto compounds for one month. The last group was administered with commercial drug Nalgin (500 mg/kg b wt). The biochemical parameters Creatinine, Protein carbonyl, 8-hydroxydeoxyguanosine (8-OHdG), VEGF, MMP-9 Inhibitor, and IL-10 were estimated using ELISA kits and Glutathione (G.S.H.), Superoxide dismutase (S.O.D.), Catalase (C.A.T.) and Nitric Oxide (NO) were analyzed manually. The correlation was analyzed through Pearson's correlation matrix. All the parameters were significantly raised in the positive control group, indicating significant inflammation. At the same time, the levels of the foresaid biomarkers were decreased in the serum in all the other groups treated with the three phytocompounds in different dose patterns. However, the best recovery was observed in the group where the three active compounds were administered concomitantly. The correlation matrix indicated a significant positive correlation of IL-10 vs VEGF (r = 0.749**, p = 0.009), MMP-9 inhibitor vs SOD (r = 0.748**, p = 0.0 21). The study concluded that the three phytocompounds ß-sitosterol, ß-amyrin, and epiafzelechin are important anticancer agents which can target the cancerous biomarkers and might be used as a better therapeutic approach against colon cancer soon.

Patient Perspectives and Side-Effects Experience on Chemotherapy of Non-Small Cell Lung Cancer: A Qualitative Study.

Purpose: This study aimed to explore patients' experiences of palliative chemotherapy for non-small cell lung cancer (NSCLC), how patients adapt to their new and challenging life after chemotherapy, their beliefs, and their quality of life. Patients and Methods: The study used an exploratory descriptive qualitative approach that was designed to explore the experiences and side effects of NSCLC patients on chemotherapy in Pakistan. The study was designed to obtain a deeper understanding of 22 NSCLC patients' experiences, using a face-to-face approach and interviews were conducted. Patients who have completed chemotherapy agreed to participate in semi-structured interviews. Results: The data were arranged into five themes: hospital facilities and environment, patient's beliefs in alternative treatments, presenting a positive/negative face, life is for living, and health insurance coverage. The major complaints related to bad experiences of chemotherapy-induced side effects, but these patients still managed to complete the full course of their respective chemotherapy. Additionally, the current study revealed the real experience of patients with NSCLC which had been less studied. The patient's experience was summarized into four themes and several subthemes. Conclusion: This study aid healthcare providers when deciding on treatment options that will improve shared decision-making between clinicians and treatment outcomes.

Identifying the reasons for delayed presentation of Pakistani breast cancer patients at a tertiary care hospital.

BACKGROUND: Delay in seeking health care by breast cancer patients is associated with advanced stage of disease at presentation and poor survival rates. This study aimed to identify the reasons for delayed presentation and their association with various sociodemographic variables. METHODS: A total of 200 female patients with abnormal clinical findings, ie, lump or palpable mass, were consecutively invited for this study. Diagnostic delay was defined as a consultation with a health care provider more than 3 months from the appearance of the first symptoms. Sociodemographic variables, presenting symptoms, knowledge about diseases and its symptoms, time between seeking medical attention after appearance of symptoms and causes of delayed presentation were investigated. Chi-squared and logistic regression tests for significance and associations were used. RESULTS: Among 125 women with breast cancer fulfilling the inclusion criteria, aged 24-75 years, 88.8% (n=111) presented late (≥3 months) and 59% presented with advanced stage of disease (stage III/IV). The majority (65.6%) were older than 40 years of age, 99.2% were married, 60.8% had <8 years of education, 67.2% had poor social status, and 64.8% had a negative family history of any cancer type. Almost all patients (96%) complained about the presence of a painless lump in their breast. Ignorance of disease or the presence of painless lumps in the breast and low financial resources for therapy (81.1%) were the main variables associated with delayed presentation. Educational factors (P<0.001, OR 4.682) and social status (P<0.001, OR 1.8) were also associated with delayed presentation. CONCLUSION: Our study highlighted the variables associated with delayed presentation in Pakistani breast cancer patients. A significant number of patients presented late owing to misconceptions and poor knowledge about the disease and its symptoms, while illiteracy and poor social status were the major contributing factors for delayed presentation, resulting in an advanced presentation of disease and ultimately a decreased survival rate.

Application of quasi-emulsification and modified double emulsification techniques for formulation of tacrolimus microsponges.

BACKGROUND: The present study was to develop a stable and sustained-release delivery system of tacrolimus (TCM). TCM is a macrolide antibiotic used as an immunosuppressant. It is formulated as a microsponge, which is a safe and effective delivery system with reduced side effects. MATERIALS AND METHODS: The method used to prepare ethyl cellulose (EC) and xanthan gum (XG)-facilitated EC-based microsponges employed emulsification and modified double emulsification techniques. TCM-containing microsponges were prepared using varying concentrations followed by evaluation of micromeritics, compatibility of drug and excipients, production yield, drug content and entrapment efficiency, zeta potential, size distribution and drug release. RESULTS: The results showed excellent flow properties with adequate entrapment efficiency of the system and satisfactory release of active pharmaceutical ingredient. In vitro dissolution studies, which were conducted to determine the amount of drug released, illustrated a pronounced sustained effect up to 8 h. Zeta size and zeta potential analysis of microsponges confirmed the existence of micro-sized (1.99-3.09 µm) and stable particles (-15.33 to -3.38 mV), respectively. CONCLUSION: Conclusively, the applied technique and selected combination of ingredients were found suitable for the preparation of TCM-containing sustained-release microsponges.

MPD3: a useful medicinal plants database for drug designing.

Medicinal plants are the main natural pools for the discovery and development of new drugs. In the modern era of computer-aided drug designing (CADD), there is need of prompt efforts to design and construct useful database management system that allows proper data storage, retrieval and management with user-friendly interface. An inclusive database having information about classification, activity and ready-to-dock library of medicinal plant's phytochemicals is therefore required to assist the researchers in the field of CADD. The present work was designed to merge activities of phytochemicals from medicinal plants, their targets and literature references into a single comprehensive database named as Medicinal Plants Database for Drug Designing (MPD3). The newly designed online and downloadable MPD3 contains information about more than 5000 phytochemicals from around 1000 medicinal plants with 80 different activities, more than 900 literature references and 200 plus targets. The designed database is deemed to be very useful for the researchers who are engaged in medicinal plants research, CADD and drug discovery/development with ease of operation and increased efficiency. The designed MPD3 is a comprehensive database which provides most of the information related to the medicinal plants at a single platform. MPD3 is freely available at: http://bioinform.info .