Formulation optimization and in vitro characterization of rifampicin and ceftriaxone dual drug loaded niosomes with high energy probe sonication technique

The aim of the present study was to prepare niosomal formulations for dual drug therapy of ceftriaxone sodium and poorly water-soluble rifampicin by the ecological probe sonication method. Pluronic L121 and Span 60 were used as surface active agents and the optimization of the composition was made with the aid of Design of Experiment (DoE) concept. Concentration levels of charge inducing agent, dicetylphosphate (DCP), and Pluronic L121 were studied as variables. Prepared niosomes with varying concentrations of DCP and Pluronic L121 resulted in small sized niosomes with sizes ranging from 165 nm to 893 nm. During the four weeks stability testing, the particle sizes of the empty niosomes were reduced, while the particle sizes of the drug loaded niosomes were increased very slightly. The optimized formulations resulted in stable niosomes with high drug entrapment efficiencies: entrapment efficiency was 99% for rifampicin and 96% for ceftriaxone. All the niosomal formulations showed faster in vitro drug release rates as compared to bulk drug formulations. In conclusion, ceftriaxone and rifampicin loaded niosomes prepared with Pluronic L121 and Span 60 resulted in stable, small sized niosomes with high drug entrapment efficiencies and improved drug release profiles.Peer reviewe

The use of intra aortic baloon pump in patients undergoing coronary artery bypass grafting at the Aga Khan University Hospital, Karachi

Objective: To review the experience in the use of Intra Aortic Balloon Pump (IABP) in patietits undergoing Coronary Artery Bypass Grafting (CABG) at a tertiary care hospital with a new Open Heart surgery program. Design: Retrospective study. Setting: The Aga Khan University Hospital, Karachi. Patients: Medical records of all patients undergoing CABG between November 1994 and July 1997 were reviewed and those in whom IABP device was used, were included in this study. Results: A total of 15 patients had IABP suppOrt during the study period. Four surgeries were done urgently while two were emergencies. There were three mortalities. Ejection fractions in all hut one patient were impaired. Among the surviving patients, the average pre-IABP Cardiac Index was 2.6 litres/mm/meter2 which registered an average increase of 21.15% after the initiation of the IABP. The Pulmonary Artery Wedge Pressure also showed an average reduction of 29.11% from the pre IABP levels reflecting an increase in the cardiac output with the use of the IABP. Conclusion: This series represents the early experience of a new cardiac surgery center in Pakistan in the use of IABP. Although the numbers in this study are too small to derive any conclusions, the overall morbidity and mortality in this short series are within acceptable limits in the high risk patients include

Process optimization of ecological probe sonication technique for production of rifampicin loaded niosomes

The aim of the present study was to develop an optimized niosome formulation for the encapsulation of a poorly water-soluble drug by the ecological probe sonication method. Pluronic L121 and Span 60 were used as surface active agents and the optimization of the composition was made with the aid of Design of Experiment (DoE) concept. Rifampicin was used as a model drug. Concentration levels of charge inducing agent, dicetylphosphate (DCP), and Pluronic L121 were studied as variables. Prepared niosomes with varying concentrations of DCP and Pluronic L121 resulted in small sized niosomes with sizes ranging from 190 nm to 893 nm. During the four weeks stability testing, the particle sizes were reduced slightly. The formulation containing 2 mg of DCP resulted in most stable niosomes with 75.37% entrapment efficiency. All the niosomal formulations showed higher in vitro drug release rates as compared to bulk drug formulation. As a conclusion, rifampicin loaded niosomes prepared with Pluronic L121 and Span 60 resulted in stable, small sized niosomes with improved drug release profile.Peer reviewe

Utilization of Green Formulation Technique and Efficacy Estimation on Cell Line Studies For Dual Anticancer Drug Therapy With Niosomes

The aim of the present study was to prepare niosome formulations for the simultaneous encapsulation, dual drug therapy, of two anticancer drugs by the ecological probe sonication method. Poloxamer and sorbitan monostearate were used as surface active agents in niosomes, and the water soluble doxorubicin and poorly-water soluble paclitaxel were used as anticancer drugs. Thorough physicochemical analysis were performed for the niosomes, and their cytotoxicity and activity were evaluated on MCF-7 and PC3-MM2 cancer cell lines. Prepared niosomes were small in size with sizes ranging from 137 nm to 893 nm, and entrapment efficiencies were high, ranging from 91.24% to 99.99%. During the four weeks stability testing, the particle size remained stable. The niosomal formulations showed in vitro sustained drug release profiles for doxorubicin and clearly increased the dissolution rate of poorly water soluble paclitaxel. The incorporation of both the drugs into niosomes improved cell penetration and antiproliferative activity of the drugs PC3-MM2 cell lines. As a conclusion, doxorubicin and paclitaxel loaded niosome formulations resulted in relatively stable, small sized niosomes with improved drug release profiles, low toxicity, better cell penetration and antiproliferative activity. The niosomes showed synergistic effect due to the presence of both drugs, which can overcome multidrug resistance.Peer reviewe

Oral Co-Supplementation of Curcumin, Quercetin, and Vitamin D3 as an Adjuvant Therapy for Mild to Moderate Symptoms of COVID-19-Results From a Pilot Open-Label, Randomized Controlled Trial

Background: Curcumin, quercetin, and vitamin D3 (cholecalciferol) are common natural ingredients of human nutrition and reportedly exhibit promising anti-inflammatory, immunomodulatory, broad-spectrum antiviral, and antioxidant activities. Objective: The present study aimed to investigate the possible therapeutic benefits of a single oral formulation containing supplements curcumin, quercetin, and cholecalciferol (combinedly referred to here as CQC) as an adjuvant therapy for early-stage of symptomatic coronavirus disease 2019 (COVID-19) in a pilot open-label, randomized controlled trial conducted at Mayo Hospital, King Edward Medical University, Lahore, Pakistan. Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed, mild to moderate symptomatic COVID-19 outpatients were randomized to receive either the standard of care (SOC) (n = 25) (control arm) or a daily oral co-supplementation of 168 mg curcumin, 260 mg quercetin, and 9 µg (360 IU) of cholecalciferol, as two oral soft capsules b.i.d. as an add-on to the SOC (n = 25) (CQC arm) for 14 days. The SOC includes paracetamol with or without antibiotic (azithromycin). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test, acute symptoms, and biochemistry including C-reactive protein (CRP), D-dimer, lactate dehydrogenase, ferritin, and complete blood count were evaluated at baseline and follow-up day seven. Results: Patients who received the CQC adjuvant therapy showed expedited negativization of the SARS-CoV-2 RT-PCR test, i.e., 15 (60.0%) vs. five (20.0%) of the control arm, p = 0.009. COVID-19- associated acute symptoms were rapidly resolved in the CQC arm, i.e., 15 (60.0%) vs. 10 (40.0%) of the control arm, p = 0.154. Patients in the CQC arm experienced a greater fall in serum CRP levels, i.e., from (median (IQR) 34.0 (21.0, 45.0) to 11.0 (5.0, 16.0) mg/dl as compared to the control arm, i.e., from 36.0 (28.0, 47.0) to 22.0 (15.0, 25.0) mg/dl, p = 0.006. The adjuvant therapy of co-supplementation of CQC was safe and well-tolerated by all 25 patients and no treatment-emergent effects, complications, side effects, or serious adverse events were reported. Conclusion: The co-supplementation of CQC may possibly have a therapeutic role in the early stage of COVID-19 infection including speedy negativization of the SARS-CoV-2 RT-PCR test, resolution of acute symptoms, and modulation of the hyperinflammatory response. In combination with routine care, the adjuvant co-supplementation of CQC may possibly help in the speedy recovery from early-stage mild to moderate symptoms of COVID-19. Further research is warranted. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT0513067

Seroprevalence of anti-polio antibodies in children from polio high risk area of Afghanistan: A cross sectional survey 2017

Background: Afghanistan is one of the remaining wild-poliovirus (WPV) endemic countries. We conducted a seroprevalence survey of anti-poliovirus antibodies in Kandahar Province.Methods: Children in two age groups (6–11 months and 36–48 months) visiting Mirwais hospital in Kandahar for minor ailments unrelated to polio were enrolled. After obtaining informed consent, we collected venous blood and conducted neutralization assay to detect poliovirus neutralizing antibodies.Results: A total of 420 children were enrolled and 409/420 (97%) were analysed. Seroprevalence to poliovirus type 1 (PV1) was 97% and 100% in the younger and older age groups respectively; it was 71% and 91% for PV2; 93% and 98% for PV3. Age group (RR = 3.6, CI 95% = 2.2–5.6) and place of residence outside of Kandahar city (RR = 1.8, CI 95% = 1.2–2.6) were found to be significant risk factors for seronegativity.Conclusions: The polio eradication program in Kandahar achieved high serological protection, especially against PV1 and PV3. Lower PV2 seroprevalence in the younger age group is a result of a withdrawal of live type 2 vaccine in 2016 and is expected. Ability to reach all children with poliovirus vaccines is a pre-requisite for achieving poliovirus eradication

Effectiveness of unconditional cash transfers combined with lipid-based nutrient supplement and/or behavior change communication to prevent stunting among children in Pakistan: A cluster randomized controlled trial

Background: In Pakistan, the prevalence of stunting among children under-five years has remained above WHO critical thresholds (≥30%) over the last two decades.Objective: We hypothesized that an unconditional cash transfer (UCT) combined with lipid-based nutrient supplement (LNS) and/or social and behavior change communication (SBCC) will prevent stunting among children 6-23 months of age.Design: This was a four-arm, community-based cluster randomized controlled trial conducted in the district of Rahim Yar Khan, Pakistan. A total of 1729 children (UCT n = 434); (UCT+SBCC n = 433); (UCT+LNS n = 430) and (UCT+LNS+SBCC n = 432) were enrolled at 6 months of age and measured monthly for 18 months until the age of 24 months.Results: At 24 months of age, children who received UCT+LNS (rate ratio [RR], 0.85 [95% CI 0.74, 0.97]; P = 0.015); and UCT+LNS+SBCC (RR, 0.86 [95% CI 0.77, 0.96]; P = 0.007) had significantly lower risk of being stunted as compared to the UCT arm. No significant difference was noted among children who received UCT+SBCC (RR, 1.03 [95% CI 0.91, 1.16]; P = 0.675) in the risk of being stunted as compared to the UCT arm. The pooled prevalence of stunting among children 6-23 months was 41.7%, 44.8%, 38.5% and 39.3% in UCT, UCT+SBCC, UCT+LNS and UCT+LNS+SBCC, respectively. In pairwise comparisons, a significant impact on stunting among children in UCT+LNS (P = 0.029) and UCT+LNS+SBCC (P = \u3c0.001) was noted as compared to UCT arm.Conclusions: UCT combined with LNS and UCT+LNS+SBCC were effective in reducing the prevalence of stunting among children aged 6-23 months in marginalized populations. UCT+SBCC was not effective in reducing the child stunting prevalence.Clinical trial registration number: ClinicalTrials.gov NCT03299218

Bismuth-Doped Nano Zerovalent Iron: A Novel Catalyst for Chloramphenicol Degradation and Hydrogen Production

© In this study, we showed that doping bismuth (Bi) at the surface of Fe0 (Bi/Fe0, bimetallic iron system) - synthesized by a simple borohydride reduction method - can considerably accelerate the reductive degradation of chloramphenicol (CHP). At a reaction time of 12 min, 62, 68, 74, 95, and 82% degradation of CHP was achieved with Fe0, Bi/Fe0-1 [1% (w/w) of Bi], Bi/Fe0-3 [3% (w/w) of Bi], Bi/Fe0-5 [5% (w/w) of Bi], and Bi/Fe0-8 [8% (w/w) of Bi], respectively. Further improvements in the degradation efficiency of CHP were observed by combining the peroxymonosulfate (HSO5-) with Bi/Fe0-5 (i.e., 81% by Bi/Fe0-5 and 98% by the Bi/Fe0-5/HSO5- system at 8 min of treatment). Interestingly, both Fe0 and Bi/Fe0-5 showed effective H2 production under dark conditions that reached 544 and 712 μM by Fe0 and Bi/Fe0-5, respectively, in 70 mL of aqueous solution containing 0.07 g (i.e., at 1 g L-1 concentration) of the catalyst at ambient temperature