Adaptation of Quality by Design-Based Development of Isradipine Nanostructured–Lipid Carrier and Its Evaluation for In Vitro Gut Permeation and In Vivo Solubilization Fate

The present study demonstrated the systematic adaptation of quality by design-integrated approach for the development of novel nanostructured lipid carrier (NLC) of an anti-hypertensive drug isradipine (ISD) to address the inherent challenges such as low solubility and low oral bioavailability. Plackett-Burman design was used for preliminary screening of significant process and formulation variables (p <0.05), which were further processed using Box-Behnken design for the attainment of optimization goal that is, mean particle size (85.7 ± 7.3 nm), drug entrapment efficiency (87.4 ± 3.29%), and in vitro drug release characteristics (92.89 ± 5.47%). The optimized ISD-NLC formulation also demonstrated well-dispersed uniform-shaped particles (polydispersity index 0.207 ± 0.029), high gastrointestinal fluid stability (zeta potential ?10.17 ± 0.59 mV), and higher in vitro gut permeation (21.69 ± 2.38 μg/cm² of ISD-NLC as compared to 11.23 ± 1.74 μg/cm² in ISD suspension). Furthermore, lipolysis studies were performed for the purpose of in vivo fate, and significantly higher drug content of ISD from ISD-NLC in aqueous phase was found (72.34 ± 4.62%) as compared to drug suspension (3.01 ± 0.91%). Relative bioavailability of ISD-NLC and ISD suspension was increased by 4.2-fold and 1.78-fold in the absence and presence of cycloheximide which is a lymphatic uptake inhibitor revealing lymphatic uptake of ISD-NLC in bioavailability improvement. Hence, systematic adaptation of quality by design integrated approach improved gut permeation and potential solubilizaton fate (dynamic lipolysis) of ISD-NLC, which further improved the lymphatic uptake and biodistribution of drug thereby promisingits in vivo prospect and clinical efficacy.     

Design,synthesis and evaluation of alkylphosphocholine-gefitinib conjugates as multitarget anticancer agents

The evolving resistance to the currently used chemotherapeutic agents requires continuous efforts to develop new anticancer agents overcoming resistance and with lower side effects. Polypharmacology via designing a single molecule intercepting multiple signaling pathways is more effective than targeting a single one. Several alkylphosphocholines show anticancer activity via inhibition of Akt phosphorylation. On the other hand, several molecules having quinazoline scaffold elicit anticancer activity through inhibition of epidermal growth factor receptor (EGFR) tyrosine kinases. We report our efforts to develop alkylphosphocholines-gefitinib conjugates as multitarget anticancer agents. The antiproliferative activities of the newly synthesized compounds were evaluated against cell lines representing lung, breast, liver and skin cancers. In addition, the capability of the newly synthesized compounds to inhibit Akt phosphorylation and EGFR tyrosine kinases were determined. The results emphasized the influence of the linkers’ length on the elicited bioactivity. The long chain linkers possessing conjugates were more active regarding both of the elicited antiproliferative effect and inhibition of Akt phosphorylation, while maintained the ability to inhibit EGFR tyrosine kinases. Their cytotoxic activities were superior or comparable to erlotinib and miltefosine.     

Risk modeling of non-communicable diseases using socio-demographic characteristics,lifestyle and family disease history among university students in Bangladesh

Aim

The objective of this study was to determine risk factors for non-communicable diseases (NCDs) on the basis of socio-demographic characteristics, lifestyle-related determinants, environmental and psychological characteristics, and individual and family disease history among university students in Bangladesh.

Study design

Cross-sectional survey.

Methods

Using the WHO STEPwise approach for NCDs, a cross-sectional study was conducted among 1,140 students. The collected data were analyzed using the Statistical Package for Social Sciences (SPSS) software, version 22.

Results

In all, 29.2% of the respondents (BMI?≥?23.00 kg/m²) were overweight and/or obese, and almost two-thirds (65%) of them did not take part in any physical activity (PA). A third (33.3%, p?=?0.002) of male smokers reported health problems and it was found that environmental tobacco smoke (ETS) was significantly responsible for developing asthma (OR?=?0.55; CI?=?0.33–0.93). Individual and family history of NCDs was statistically significant for obesity and asthma and considerably increased the odds ratio for heart disease.

Conclusion

This study shows that the number of students suffering from different types of NCDs is not negligible. Their lifestyle and family history of NCDs are responsible for this to a significant extent. Urgent initiatives should be taken to rein in the spread of NCDs among the youth of Bangladesh.

     

PVA-PEG physically cross-linked hydrogel film as a wound dressing: experimental design and optimization

The development of hydrogel films as wound healing dressings is of a great interest owing to their biological tissue-like nature. Polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogels loaded with asiaticoside, a standardized rich fraction of Centella asiatica, were successfully developed using the freeze–thaw method. Response surface methodology with Box–Behnken experimental design was employed to optimize the hydrogels. The hydrogels were characterized and optimized by gel fraction, swelling behavior, water vapor transmission rate and mechanical strength. The formulation with 8% PVA, 5% PEG 400 and five consecutive freeze–thaw cycles was selected as the optimized formulation and was further characterized by its drug release, rheological study, morphology, cytotoxicity and microbial studies. The optimized formulation showed more than 90% drug release at 12?hours. The rheological properties exhibited that the formulation has viscoelastic behavior and remains stable upon storage. Cell culture studies confirmed the biocompatible nature of the optimized hydrogel formulation. In the microbial limit tests, the optimized hydrogel showed no microbial growth. The developed optimized PVA/PEG hydrogel using freeze–thaw method was swellable, elastic, safe, and it can be considered as a promising new wound dressing formulation.     

Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate cancer cells

Resveratrol (RL), a natural polyphenol, is known for its diverse biological effects against various human cancer cell lines. But low aqueous solubility, poor bioavailability, and stability limit its efficacy against prostate cancer. In this study polymeric nanoparticles encapsulating resveratrol (RLPLGA) were designed and their cytotoxic and mode of apoptotic cells death against prostate cancer cell line (LNCaP) was determined. Nanoparticles were prepared by solvent displacement method and characterized for particle size, TEM, entrapment efficiency, DSC and drug release study. RLPLGA exhibited a significant decrease in cell viability with 50% and 90% inhibitory concentration (IC₅₀ and IC₉₀) of 15.6?±?1.49 and 41.1?±?2.19?μM respectively against the LNCaP cells. This effect was mediated by apoptosis as confirmed by cell cycle arrest at G1-S transition phase, externalization of phosphatidylserine, DNA nicking, loss of mitochondrial membrane potential and reactive oxygen species generation in LNCaP cells. Furthermore, significantly greater cytotoxicity to LNCaP cells was observed with nanoparticles as compared to that of free RL at all tested concentrations. RLPLGA nanoparticles presented no adverse cytotoxic effects on murine macrophages even at 200?μM. Our findings support the potential use of developed resveratrol loaded nanoparticle for the prostate cancer chemoprevention/ chemotherapy with no adverse effect on normal cells.     

Development and validation of UPLC-PDA method for concurrent analysis of bergenin and menisdaurin in aerial parts of Flueggea virosa (Roxb. ex Willd.)

Bergenin and menisdaurin are biologically active components which are found in plant Flueggea virosa (Phyllanthaceae). Bergenin has pharmacological actions such as chemopreventive and antihepatotoxic while menisdaurin has an anti-viral activity which needs its evaluation by an analytical method (UPLC-PDA method) that can be applied to the quality control of pharmaceutical preparations. The developed UPLC-PDA method was applied for identification and quantification of standards bergenin and menisdaurin in the methanol extract of F. virosa (FVME). The analysis was carried out using Eclipse C18 (4.6?×?100?mm, 3.5?µm) UPLC column. The optimized chromatographic condition was achieved at 0.16?mL/min flow rate using gradient system with acetonitrile and water as mobile phase. Both biomarkers were measured at λ_max 235?nm in PDA detector at ambient temperature. The developed method furnished sharp and intense peaks of menisdaurin and bergenin at Rt?=?2.723 and 3.068?min, respectively along with r2?>?0.99 for both. The recoveries of bergenin and menisdaurin were found in the range of 99.37–101.49% and 98.20–100.08%, respectively. With other validation data, including precision, specificity, accuracy, and robustness, this method demonstrated excellent reliability and sensitivity. The separation parameters i.e. retention, separation, and resolution factors for resolved standards (bergenin and menisdaurin) were >1, which showed good separation. The quantity of bergenin and menisdaurin in the FVME sample was found as 15.16 and 3.28% w/w, respectively. The developed UPLC-PDA method could be conveniently adopted for the routine quality control analysis.     

Antibacterial effects of 18 medicinal plants used by the Khyang tribe in Bangladesh

Context: The resistance of bacteria to antibiotics is raising serious concern globally. Asian medicinal plants could improve the current treatment strategies for bacterial infections. The antibacterial properties of medicinal plants used by the Khyang tribe in Bangladesh have not been investigated.

Objective: The present study examines the antibacterial properties of 18 medicinal plants used by the Khyang tribe in day-to-day practice against human pathogenic bacteria.

Materials and methods: Leaves, bark, fruits, seeds, roots and rhizomes from collected plants were successively extracted with hexane, ethyl acetate and ethanol. The corresponding 54 extracts were tested against six human pathogenic bacteria by broth microdilution assay. The antibacterial mode of actions of phytoconstituents and their synergistic effect with vancomycin and cefotaxime towards MRSA was determined by time-killing assay and synergistic interaction assay, respectively.

Results and discussion: Hexane extract of bark of Cinnamomum cassia (L.) J. Presl. (Lauraceae) inhibited the growth of MRSA, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii with MIC values below 100 µg/mL. From this plant, cinnamaldehyde evoked at 4?×?MIC in 1?h an irreversible decrease of MRSA count Log10 (CFU/mL) from 6 to 0, and was synergistic with vancomycin for MRSA with fractional inhibitory concentration index of 0.3.

Conclusions: Our study provides evidence that the medicinal plants in Bangladesh have high potential to improve the current treatment strategies for bacterial infection.     

Seasonal variation in the association between household food insecurity and child undernutrition in Bangladesh: Mediating role of child dietary diversity

Household food insecurity (HFI) and child dietary diversity (CDD) are variable across seasons. We examined seasonal variation in HFI and child undernutrition association and tested how CDD mediates this association. We analyzed data for 26,353 children aged 6–59 months drawn from nationally representative cross-sectional Food Security and Nutrition Surveillance Project data collected during 2012–2014 in Bangladesh across three seasons annually: Post-Aman harvest (January–April); Monsoon (May–August); and Post-Aus harvest (September–December). Multivariable logistic regression analysis adjusted for individual, maternal, household and geographical characteristics reveals that children of food-insecure households were more likely than food-secure households to be stunted (adjusted odds ratio, AOR: 1.12; 95% confidence interval, CI: 1.02–1.23; p < 0.05), wasted (AOR: 1.21; 95% CI: 1.05–1.39; p < 0.01) and underweight (AOR: 1.16; 95% CI: 1.04–1.3; p < 0.01). CDD mediated 6.1% of the total effect of HFI on underweight. These findings varied across seasons. HFI was associated with greater odds of underweight during Monsoon (AOR: 1.32; 95% CI: 1.08–1.62; p < 0.01) and Post-Aus (AOR: 1.21; 95% CI: 1.06–1.37; p < 0.01) while wasting during Post-Aus (AOR: 1.65; 95% CI: 1.35–2.01; p < 0.001). CDD largely mediated the total effect of HFI on underweight during the Post-Aman in 2012–2014 (23.2%). CDD largely mediated the total effect of HFI on wasting (39.7%) during Post-Aman season in 2014 and on underweight (13.7%) during the same season in 2012. These findings demonstrate that HFI is seasonally associated with child undernutrition and mediated by CDD as well in Bangladesh and seasonality and diversity should be considered while designing appropriate population-level food-based interventions to resolve child undernutrition.     

Use of designing for behaviour change framework in identifying and addressing barriers to and enablers of animal source feeding to children ages 8–23 months in Bandarban Hill District in Bangladesh: Implications for a nutrition-sensitive agriculture programme

Inadequate diet quality is a cause of undernutrition among children 6–23 months of age in Bangladesh, particularly in remote and isolated areas such as Bandarban District. Feeding animal source foods can help to combat stunting and wasting problems among children, but it may not be accessible or acceptable. A barrier analysis using the Designing for Behavior Change Framework was conducted in Bandarban district with participants from 4 ethnic groups, to explore potential barriers and key motivators by examining 12 behavioural determinants of consumption of animal-source food in complementary feeding for children 8–23 months. Data were collected from 45 mothers of children 8–23 months, who provided animal-source foods to their children (doers), and from 45 mothers who did not (non-doers), for a total of 90 interviews. Nine determinants were statistically significantly different between doers and non-doers as follows: self-efficacy, positive consequences, negative consequences, social norms, access, reminders, perceived risk, perceived severity and perceived action efficacy. Nearby access to purchase animal-source foods, rearing poultry or livestock at home and the support of household and community members are enablers to feeding animal-source food. In contrast, these same factors are barriers for non-doers. The lack of money to spend on animal-source foods is also a barrier. An integrated nutrition-sensitive and gender-transformative animal-based food production, and inclusive market programme could increase access to meat and eggs at the household level, increase opportunities to earn income and support gender-equitable household workloads and decision-making for optimal child feeding.     

Unexpected complication of arteriovenous fistula of the left common carotid to internal jugular vein following central venous catheterization

Incidence of inadvertent arterial puncture secondary to central venous catheter insertion is not common with an arterial puncture rate of<1%.This is due to the advancements and wide availability of ultrasound to guide its insertion.Formation of arteriovenous fistula after arterial puncture is an unexpected complication.Till date,only five cases(including this case)of acquired arteriovenous fistula formation has been described due to inadvertent common carotid puncture.The present case is a 26-year-old man sustained traumatic brain injuries,chest injuries and multiple bony fractures.During resuscitative phase,attempts at left central venous catheter via left internal jugular vein under ultrasound guidance resulted in inadvertent puncture into the left common carotid artery.Surgical neck exploration revealed that the catheter had punctured through the left internal jugular vein into the common carotid artery with formation of arteriovenous fistula.The catheter was removed successfully and common carotid artery was repaired.Postoperatively,the patient recovered and clinic visits revealed no neurological deficits.From our literature review,the safest method for removal is via endovascular and open surgical removal.The pull/push technique(direct removal with compression)is not recommended due to the high risk for stroke,bleeding and hematoma formation.