AIM OF THE STUDY: To develop a natural biodegradable macromolecule i.e. Chitosan (CS)-coated-DAUN-PLGA-poly(lactic-co-glycolic acid)-Nanoparticles (NPs) with an aim to improve oral-DAUN bioavailability and to develop as well as validate UHPLC-MS/MS (ESI/Q-TOF) method for plasma quantification and pharmacokinetic analysis (PK) of DAUN.
RESULTS: A particle size (198.3 ± 9.21 nm), drug content (47.06 ± 1.16 mg/mg) and zeta potential (11.3 ± 0.98 mV), consisting of smooth and spherical shape was observed for developed formulation. Cytotoxicity studies for CS-DAUN-PLGA-NPs revealed; a comparative superiority over free DAUN-S (i.v.) in human breast adenocarcinoma cell lines (MCF-7) and a higher permeability i.e. 3.89 folds across rat ileum, as compared to DAUN-PLGA-NPs (p oral administration of DAUN is reported in this study which is can be utilized as an alternate for intravenous therapy.
Materials and Methods: This was a retrospective cohort study that included all patients with AF who were treated with NOACs (dabigatran or rivaroxaban) in HKL and HSDG. Data were obtained from medical records and pharmacy databases. Adherence was assessed using proportion of days covered (PDC) over a 1-year duration. High adherence was defined as PDC ≥80%. A gap of >60 days between two consecutive refills was used to define non-persistence.
Result: There were 281 patients who met the inclusion criteria, with 54.1% (n = 152) male. There were 75.1% (n = 211) patients on dabigatran and others on rivaroxaban. Only 66.9% (n = 188) of patients achieved high adherence with PDC ≥80% and 69.8% (n = 196) were persistence with >60-day gap over 12 months. Adherence and persistence were both influenced by treatment center, whereas polypharmacy only influenced adherence.
Conclusion: Overall adherence and persistence to NOACs were suboptimal and varied between treatment centers, potentially due to institution-specific administrative and clinical practice differences. Clinical care and outcomes can potentially be optimized by identifying factors affecting adherence and persistence and by implementing interventions to improving them.
OBJECTIVES: The present study was aimed to fabricate the capecitabine as smart pH-responsive hydrogel network to efficiently facilitate its oral delivery while shielding its stability in the gastric media.
METHODS: The smart pH sensitive HP-β-CD/agarose-g-poly(MAA) hydrogel network was developed using an aqueous free radical polymerization technique. The developed hydrogels were characterized for drug-loading efficiency, structural and compositional features, thermal stability, swelling behaviour, morphology, physical form, and release kinetics. The pH-responsive behaviour of developed hydrogels was established by conducting the swelling and release behaviour at different pH values (1.2 and 7.4), demonstrating significantly higher swelling and release at pH 7.4 as compared with pH 1.2. The capecitabine-loaded hydrogels were also screened for acute oral toxicity in animals by analysing the body weight, water and food intake, dermal toxicity, ocular toxicity, biochemical analysis, and histological examination.
RESULTS: The characteristic evaluations revealed that capecitabine (anticancer agent) was successfully loaded into the hydrogel network. Capecitabine loading was ranged from 71.22% to 90.12%. An interesting feature of hydrogel was its pH-responsive behaviour which triggers release at basic pH (94.25%). Optimum swelling (95%) was seen at pH 7.4. Based upon regression coefficient R2 (0.96 - 0.99) best fit model was zero order. The extensive toxicity evaluations evidenced good safety profile with no signs of oral, dermal or ocular toxicities, as well as no variations in blood parameters and histology of vital organs.
CONCLUSION: Our findings conclusively evinced that the developed hydrogel exhibited excellent pharmaceutical and therapeutic potential and thus can be employed as pH-responsive system for controlled delivery of anticancer agents.
METHODOLOGY: The trial is reported according to the Preferred Reporting Items for RAndomized Trials in Endodontics (PRIRATE) 2020 guidelines. The protocol was registered at the clinical trial registry (India) (CTRI/2019/06/019818). In total, 160 patients, assigned to four groups, received orally either 20 mg piroxicam, 20 mg prednisolone, 4 mg dexamethasone or a placebo 60 min before root canal treatment. Patients recorded their postoperative pain intensity at 6, 12, 24, 48 and 72 h using a 10-cm visual analogue scale. Intergroup comparison was performed using Kruskal-Wallis tests with post hoc analysis using Dunns test. Incidence of pain was analysed using chi-square tests. A P value 0.05). One patient in the piroxicam group reported gastritis, whereas no adverse effects were recorded in other groups.
CONCLUSION: Preoperative oral administration of a single dose of 4 mg dexamethasone, 20 mg piroxicam or 20 mg prednisolone reduced the incidence and severity of postoperative pain following single-visit root canal treatment compared to a placebo in patients with symptomatic irreversible pulpitis and symptomatic apical periodontitis up to 24 h. The odds of postoperative pain at 24 h for patients premedicated with 4 mg dexamethasone or 20 mg piroxicam or 20 mg prednisolone were 5.3 times, 3.4 times and 2.5 times less compared to the placebo, respectively.
RESULTS: The LACV was evaluated for its colonization potential, reactogenicity, immunogenicity and protective efficacy in animal models after its storage at room temperature for 140 days. In suckling mice colonization assay, the LACV recorded the highest recovery of (7.2 × 107 CFU/mL) compared to those of unformulated VCUSM14P (5.6 × 107 CFU/mL) and the WT O139 strain (3.5 × 107 CFU/mL). The LACV showed no reactogenicity even at an inoculation dose of 104-106 CFU/mL in a rabbit ileal loop model. The rabbits vaccinated with the LACV or unformulated VCUSM14P survived a challenge with WT O139 and showed no signs of diarrhoea or death in the reversible intestinal tie adult rabbit diarrhoea (RITARD) model. Vaccinated rabbits recorded a 275-fold increase in anti-CT IgG and a 15-fold increase in anti-CT IgA antibodies compared to those of rabbits vaccinated with unformulated VCUSM14P. Vibriocidal antibodies were increased by 31-fold with the LACV and 14-fold with unformulated VCUSM14P.
CONCLUSION: The vaccine formulation mimics a natural infection, is non-reactogenic and highly immunogenic in vivo and protects animals from lethal wild-type V. cholerae O139 challenge. The single dose LACV formulation was found to be stable at room temperature (25 ± 2 °C) for 140 days and it would result in significant cost savings during mass cholera vaccination campaigns.