Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application

Raloxifene hydrochloride, a highly effective drug for the treatment of invasive breast cancer and osteoporosis in post-menopausal women, shows poor oral bioavailability of 2%. The aim of this study was to develop, statistically optimize, and characterize raloxifene hydrochloride-loaded transfersomes for transdermal delivery, in order to overcome the poor bioavailability issue with the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental design. Phospholipon ® 90G, sodium deoxycholate, and sonication time, each at three levels, were selected as independent variables, while entrapment efficiency, vesicle size, and transdermal flux were identified as dependent variables. The formulation was characterized by surface morphology and shape, particle size, and zeta potential. Ex vivo transdermal flux was determined using a Hanson diffusion cell assembly, with rat skin as a barrier medium. Transfersomes from the optimized formulation were found to have spherical, unilamellar structures, with a homogeneous distribution and low polydispersity index (0.08). They had a particle size of 13

Formulation and optimization of raloxifene loaded nanotransfersomes by response surface methodology for transdermal drug delivery

Raloxifene HCl loaded transfersomes were fabricated, optimized, and characterized as carrier for transdermal delivery to overcome the poor bioavailabilty issue with the drug. Response surface methodology (RSM) was applied for optimization of the formulation with Box-Behnken experimental design. Phospholipid PC90G (A), sodium deoxycholate (SDC) (B) and sonication time (C), each at three levels, were selected as independent variables while entrapment efficiency (EE%) (Y1), vesicle size (Y2), and transdermal flux (Y3) were the response variables. The optimized formulation was further characterized for vesicular size distribution, shape, surface morphology, and zeta-potential. Response variables data were analyzed by Design expert® software and the best model for all three response variables was found to be quadratic. Formulation No13 with composition of 300mg PC90G (A), 35mg SDC (B) and 15min sonication time (C) was predicted as the optimized formulation. The optimized formulation resulted a particle size of 134±9.0 nm with 91±4.9% EE%, 6.5±1.1μg/cm2/h transdermal flux, and -2.61±0.5 mV zeta potential. Transmission electron microscopy, scanning electron microscopy, and dynamic light scattering study defined transfersomes as spherical,unilamellar structures with a homogenous distribution and low polydispersity index (0.080±0.021). Transfersomal formulation proved significantly superior in terms of amount of drug permeated and deposited in the skin, with an enhancement ratio of 6.25±1.5 and 9.25±2.4 when compared with conventional liposomes and ethanolic phosphate buffer solution of the drug respectively. Confocal scanning laser microscopy proved an enhanced permeation of coumarin-6 loaded transfersomes to the deeper layers of the skin (160 μm) as compared to the rigid liposomes (60 μm). These in-vitro findings proved that raloxifene HCl loaded transfersomal formulation could be a superior alternative to oral delivery of the drug

Transdermal permeation mechanism of sodium deoxycholate aided nano-transfersomes by Differentail Sacnning Calorimetry (DSC)

Transfersomes are lipid based nano-vesicles made of phospholipid and surfactant. Their drug permeation mechanism through the skin has been attributed to the moisture seeking tendency (xerophobia) of the lipid vesicles followed by destabilization of lipid bi-layer in the stratum corneum (SC) by surfactant1. However, structural changes of SC due to surfactant need further elucidation to know the specific role of that surfactant in doing so. The objective of this study was to evaluate drug permeation mechanism of raloxifene loaded nano-transfersomes containing sodium deoxycholate used as a surfactant. Phospholipon® 90G was used as a lipid composition in the nano-formulation2. Three different types of skin i.e. mice, guineapig, and rabbit were used for this study. The SC was detached from the rest of the skin layers with chemical treatment, thoroughly washed, and kept for drying in a vacuum desiccator. The SC samples were subjected to an ex-vivo permeation study of the transfersomal formulation for 8 hours. A control sample was prepared in a similar way, without any formulation treatment. A sample of the SC section was cut, sealed in aluminum hermetic pans and scanned using DSC at a scanning rate of 5°C per minute over the range of 25°C–125°C. The characteristic bi-layer lipid and keratin transition peaks found in the control SC samples were: 75°C, 78°C, and 95°C for mice; 820C, 900C, and 990C for guineapig; and 840C, 920C, 990C for rabbit3. However, upon treatment with sodium deoxycholate aided raloxifene nano-transfersomes, most of the peaks were shifted towards lower melting points and some of them were disappeared. This finding confirmed disruption of lipid bi-layer and denaturation of keratin in the SC layer of the investigated skin samples by nano-transfersomes with sodium deoxycholate. It also established the role of sodium deoxycholate in transdermal permeation of drug loaded nano-transfersomes formulation

Association of Physical Activity with Co-morbid Conditions in Geriatric Population

To find out association of physical activity with co-morbid conditions in geriatric population, a cross-sectional study was conducted in different cties of Pakistan in 2015. A total of 114 participants were inducted by non-probability convenience sampling technique. Data was collected after informed verbal consent by a validated questionnaire that is Rapid Assessment of Physical Activity (RAPA). Participants were categorized into two groups i.e. physically active and physically inactive. Data was entered and analyzed in SPSS version 20. There were 66 (57.9%) males and 48 (42.1%) females with mean age of 57.04±7.348 years. Among hypertensive individuals (n=43, 37.7%) there were 39 (90.7%) physically inactive, among individuals having angina (n=17, 14.9%) there were 15 (88.2%) physically inactive. Out of 37 (32.5%) diabetics, 35 (94.6%) were physically inactive. Among individuals suffering from arthritis (n=40, 35.1%), there were 38 (95%) physically inactive. A significant association was found between physical activity and diabetes and arthritis with p-value of 0.048 and 0.029 respectively. Physical activity is significantly associated with diabetes and arthritis in geriatric population. Adequate physical activity should be performed to reduce the risk of co-morbid conditions and improve the quality of life in geriatric population

Thrombolytic therapy in acute myocardial infarction in Pakistan.

To characterize features of acute myocardial infarction (AMI) in a Pakistani population, and assess the role of thrombolysis in our country, we studied 194 consecutive admitted patients with enzyme positive AMI. Males were affected three times more frequently; women, although affected less, had a higher incidence of complications than men. Premature coronary artery disease (CAD) was present in 50% patients presenting with AMI. An unusually high incidence of anterior wall myocardial infarction (39%) was seen. Complications were frequent with a predominance of LV failure symptoms. Cardiogenic shock was associated with a very high mortality, in excess of 93%. Streptokinase (SK) was administered in 60% patients with suspected transmural AMI. A statistically significant reduction in mortality was seen in the group that received SK (15.2%) compared to those who did not receive SK (24.7%), (p = \u3c 0.05)

Synthesis and liquid crystalline behaviour of substituted (E)-phenyl-4-(phenyldiazenyl) benzoate derivatives and their photo switching ability

Azobenzene derivatives containing phenyl/4-halogen-phenyl 4-{(E)-[4-(pent-4-en-1-yloxy)phenyl] diazenyl}benzoate group with different electronegative substituent (H, F, Cl, Br and I) at other end was synthesised. These azo-based benzoate derivatives have been characterised by FTIR, 1H-NMR, 13C-NMR, elemental analyser, POM and UV-Vis spectroscopy. Photosaturation at 358 nm obtained after 82 s of UV irradiation and the longest thermal back relaxation time of 45 h recorded by UVVis. The azo derivative could be possible photolock under UV light, as observed by the improved thermal back relaxation time. The resulting photolockable chain of azobenzene might prove valuable in the development of optical device application. These azobenzene moieties also exhibit liquid crystalline behaviour with respect to the halogen substitution as an electron withdrawing group shows that strong structure property relationship exists among them

Thrombosis with thrombocytopenia syndrome after administration of AZD1222 or Ad26.COV2.S vaccine for COVID-19: A systematic review

Background: Cases of thrombosis with thrombocytopenia syndrome (TTS) have been reported following vaccination with AZD1222 or Ad26.COV2.S. This review aimed to explore the pathophysiology, epidemiology, diagnosis, management, and prognosis of TTS.Methods: A systematic review was conducted to identify evidence on TTS till 4th September 2021. Case reports and series reporting patient-level data were included. Descriptive statistics were reported and compared across patients with different sexes, age groups, vaccines, types of thrombosis, and outcomes.Findings: Sixty-two studies reporting 160 cases were included from 16 countries. Patients were predominantly females with a median age of 42.50 (22) years. AZD1222 was administered to 140 patients (87·5%). TTS onset occurred in a median of 9 (4) days after vaccination. Venous thrombosis was most common (61.0%). Most patients developed cerebral venous sinus thrombosis (CVST; 66.3%). CVST was significantly more common in female vs male patients (p = 0·001) and in patients aged \u3c45 years vs ≥45 years (p = 0·004). The mortality rate was 36.2%, and patients with suspected TTS, venous thrombosis, CVST, pulmonary embolism, or intraneural complications, patients not managed with non-heparin anticoagulants or IVIG, patients receiving platelet transfusions, and patients requiring intensive care unit admission, mechanical ventilation, or inpatient neurosurgery were more likely to expire than recover.Interpretation: These findings help to understand the pathophysiology of TTS while also recommending diagnostic and management approaches to improve prognosis in patients.Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors