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Background: The study was designed to evaluate the impact of pharmacist-led clinical interventions on the health-related quality of life among tuberculosis patients in Pakistan.Methods: A randomized, controlled prospective study was carried out in a Pakistan Institute of Medical Sciences hospital tuberculosis (TB) control center. Participants who visited the TB center between September 2020 and December 2021 were randomly assigned to two clusters, the usual care group (UC group) vs. the intervention group (pharmaceutical care group), in a 1:1 ratio by a simple envelope technique. In the intervention group, a patient received centered care that encompassed informed decision-making, which can increase the quality of care and monitoring of adverse drug events. However, the control group received routine TB treatment at the hospital. The EuroQol-5D-3L instrument was used to assess the health-related quality of life (HRQoL) at the baseline and in the third and sixth months of the treatment time period.Results: A total of 503 patients were eligible, of which only 426 patients were included in this study. At the end of the study, n = 205 of the patients in the intervention group and n = 185 of those in the control group were analyzed. In the intervention group, the EQ-5D-3L health utility score improved significantly (p < 0.001) (from the baseline mean ± SD, 0.40 ± 0.36, to 6 months of treatment, 0.89 ± 0.09, while in the control group from 0.42 ± 0.35 to 0.78 ± 0.27). In multivariate regression analysis, the variables that remained statistically associated (p < 0.001) with the HRQoL (unstandardized β [95% confidence interval]) of the control group were as follows: gender, female vs. male (-0.039 [-0.076 to -0.003]); body weight, less than 40 kg vs. more than 40 kg (-0.109 [-0.195 to -0.024]); patients with any comorbidity vs. without comorbidity (-0.136 [-0.252 to -0.020]); and smokers vs. non-smokers (-0.204 [-0.291 to -0.118]). The study did not find any statistically significant associations between the intervention group’s variables and the HRQoL.Conclusion: Patient-centered care interventions led by pharmacists as part of care coordination enhanced the HRQoL for TB patients significantly. According to this study, clinical pharmacists should be included in the interdisciplinary clinical staff for TB patient management.

Retinoids are considered the mainstay treatment for moderate to severe acne. Adapalene, a third-generation retinoid, has physiochemical properties which hinder the effective delivery of the drug to the skin. Therefore, the current study aimed to develop and evaluate adapalene liposomal loaded gel (ADA-LP gel) for the effective management of acne to improve tolerability and delivery to targeted sites as compared to the conventional dosage form of the drug. A novel spontaneous phase transition method (SPT) was used to formulate liposomes. Liposomal formulation (ADA-LP) was prepared and optimized based on particle size, zeta potential, and PDI. Optimized formulation was further characterized by different techniques and loaded into Carbopol gel. In vitro drug release, ex vivo permeation, and in vivo studies were performed using the prepared adapalene-loaded liposomal-based gel. The in vivo study was done employing the testosterone-induced acne model in mice. The optimized formulation had a size of 181 nm, PDI 0.145, and a zeta potential of −35 mV, indicating that the formulation was stable. Encapsulation efficiency was 89.69 ± 0.5%. ADA-LPs were loaded into the gel. Prepared ADA-LP showed a 79 ± 0.02% release of drug in a sustained manner, within 24 h. The ex vivo permeability study showed a total of 43 ± 0.06 µg/cm2 of drug able to permeate through the skin within 24 h. Moreover, only 28.27 ± 0.04% was retained on the epidermis. The developed ADA-LP gel showed significant improvement in the acne lesions in mice with no visible scars and inflammation on the skin. Therefore, ADA-LP-based gel could be a promising carrier system for the safe and effective delivery of Adapalene.

Burns are highly traumatizing injuries that can be complicated by various microbial infections, leading to morbidity and mortality. The ultimate goal of burn therapy is to prevent any microbial infection and rapid wound healing with epithelization. The current study aimed to develop and investigate the potential of nanoemulsion-based cosmetotherapeutic lotion of silver sulfadiazine (SSD) for increased antimicrobial activity to treat burn injuries. Silver sulfadiazine is the standard topical treatment for burn patients, but is allied with major limitations of poor solubility, low bioavailability, and other hematologic effects, hindering its pharmaceutical applications. The nanoformulation was fabricated through the ultrasonication technique and optimized by selecting various parameters and concentrations for the formation of water-in-oil (w/o) emulsion. The optimized formulation depicts a smaller particle size of 213 nm with an encapsulation efficiency of approx. 80%. Further, nanoemulsion-based SSD lotion by utilizing argan oil as a cosmetotherapeutic agent was prepared for scar massaging with improved permeation properties. The designed cosmeceutical formulation was characterized in terms of physical appearance, refractive index, particle size, encapsulation efficiency, and biocompatibility. The compatibility of the formulation ingredients were determined through FTIR (Fourier Transform Infrared Spectroscopy). The formulated nanolotion containing SSD demonstrated superior antimicrobial activities against different bacterial strains in comparison to commercialized burn creams.

This research was designed to identify thermodynamically and kinetically stable lipidic self-emulsifying formulations through simple energy dynamics in addition to highlighting and clarifying common ambiguities in the literature in this regard. Proposing a model study, this research shows how most of the professed energetically stable systems are actually energetically unstable, subjected to indiscriminate and false characterization, leading to significant effects for their pharmaceutical applications. A self-emulsifying drug delivery system (SEDDS) was developed and then solidified (S-SEDDS) using a model drug finasteride. Physical nature of SEDDS was identified by measuring simple dynamics which showed that the developed dispersion was thermodynamically unstable. An in vivo study of albino rats showed a three-fold enhanced bioavailability of model drug with SEDDS as compared to the commercial tablets. The study concluded that measuring simple energy dynamics through inherent properties can distinguish between thermodynamically stable and unstable lipidic systems. It might lead to correct identification of a specific lipidic formulation and the application of appropriate characterization techniques accordingly. Future research strategies include improving their pharmaceutical applications and understanding the basic differences in their natures.

Methotrexate (MTX), the gold standard against psoriasis, poses severe problems when administered systemically viz increased toxicity, poor solubility and adverse reactions. Hence, a topical formulation of MTX for the management of psoriasis can be an effective approach. The present study aimed to develop an MTX based nanoparticle-loaded chitosan hydrogel for evaluating its potential efficacy in an imiquimod-induced psoriatic mice model. MTX-NPs loaded hydrogel was prepared and optimized using the o/w emulsion solvent evaporation method. Particle size, zeta potential, entrapment efficiency, in vitro drug release, ex vivo permeation, skin irritation and deposition studies were performed. Psoriatic Area and Severity Index (PASI) score/histopathological examinations were conducted to check the antipsoriatic potential of MTX-NPs loaded hydrogel using an imiquimod (IMQ)-induced psoriatic model. Optimized MTX-NPs showed a particle size of 256.4 ± 2.17 nm and encapsulation efficiency of 86 ± 0.03%. MTX-NPs loaded hydrogel displayed a 73 ± 1.21% sustained drug release in 48 h. Ex vivo permeation study showed only 19.95 ± 1.04 µg/cm2 of drug permeated though skin in 24 h, while epidermis retained 81.33% of the drug. A significant decrease in PASI score with improvement to normalcy of mice skin was observed. The developed MTX-NPs hydrogel displayed negligible signs of mild hyperkeratosis and parakeratosis, while histopathological studies showed healing signs of mice skin. So, the MTX-NPs loaded hydrogel can be a promising delivery system against psoriasis.

In this paper, analysis of outage, channel capacity and symbol error rate (SER) analysis of Device-to- Device (D2D) communication systems is presented. The received signals of D2D communication system are affected by multiple co-channel interferers. The channel gain powers are considered to follow Gamma distribution. An expression for probability density function (PDF) expression of the signal-to-interference ratio (SIR) is presented. Based on expression of the PDF, the expressions for the outage, channel capacity and symbol error rate (SER) are presented. The performance of D2D communication system is then numerically analyzed and discussed under various conditions of channel fading and interference.

Vesicular drug delivery systems have gained wide attention in the field of nanotechnology. Among them proniosomes become the superior over other vesicular carriers. Proniosomes are dry formulations of water soluble nonionic surfactant coated carrier system which immediately forms niosomes upon hydration. They have the capability to overcome the instability problems associated with niosomes and liposomes and have the potential to improve solubility, bioavailability, and absorption of various drugs. Furthermore, they offer versatile drug delivery concept for enormous number of hydrophilic and hydrophobic drugs. They have the potential to deliver drugs effectively through different routes at specific site of action to achieve controlled release action and reduce toxic effects associated with drugs. This review discusses the general preparation techniques of proniosomes and mainly focus on the applications of proniosomes in drug delivery and targeting. Moreover, this review demonstrates critical appraisal of the literature for proniosomes. Additionally, this review extensively explains the potential of proniosomes in delivering drugs via different routes, such as oral, parenteral, dermal and transdermal, ocular, oral mucosal, vaginal, pulmonary, and intranasal. Finally, the comparison of proniosomes with niosomes manifests the clear distinction between them. Moreover, proniosomes need to be explored for proteins and peptide delivery and in the field of nutraceuticals and develop pilot plant scale up studies to investigate them in industrial set up.

Abstract Science and technology have always been the vitals of human’s struggle, utilized exclusively for the development of novel tools and products, ranging from micro- to nanosize. Nanotechnology has gained significant attention due to its extensive applications in biomedicine, particularly related to bio imaging and drug delivery. Various nanodevices and nanomaterials have been developed for the diagnosis and treatment of different diseases. Herein, we have described two primary aspects of the nanomedicine, i.e., in vivo imaging and drug delivery, highlighting the recent advancements and future explorations. Tremendous advancements in the nanotechnology tools for the imaging, particularly of the cancer cells, have recently been observed. Nanoparticles offer a suitable medium to carryout molecular level modifications including the site-specific imaging and targeting. Invention of radionuclides, quantum dots, magnetic nanoparticles, and carbon nanotubes and use of gold nanoparticles in biosensors have revolutionized the field of imaging, resulting in easy understanding of the pathophysiology of disease, improved ability to diagnose and enhanced therapeutic delivery. This high specificity and selectivity of the nanomedicine is important, and thus, the recent advancements in this field need to be understood for a better today and a more prosperous future.

An audit of the antibiotic prophylaxis in surgical procedures is the basic area of antimicrobial stewardship programme. The current research aimed to evaluate the adherence-proportion of the pre-operative antibiotic prophylaxis (PAP) practices in common elective surgical procedures. It was an eight-month (January 2017 to August 2017) observational cross-sectional patients' treatment record-based study conducted at two tertiary care teaching hospitals of Islamabad, Pakistan. We investigated the three most commonly performed elective general surgical procedures at the hospitals in adults aged > 18 years with no previous infection or surgery. The required data were extracted from the medical charts. Current prescribing practices were compared with the standard prescribing guidelines. A total of 660 (Government Hospital (GH), n = 330 and Private Hospital (PH), n = 330) procedures were observed. The most commonly performed elective general surgical procedures were laparoscopic cholecystectomy 307/660 (46.5%), followed by direct inguinal hernia 197/660 (29.8%) and total thyroidectomy 156/660 (23.6%). Non-use of PAP was observed in 64/660 (9.7%) cases. PAP was given to 90.3% (n = 596/660) cases (300/330 (90.9%) patients in GH and 296/330 (89.7%) in PH; P = 0.599). Based on the existing guidelines, the choice of antibiotics was correct in only 4.2% (25/596) patients (10/300; 3.3% cases at GH and 15/296; 5% at PH). The appropriate use of antibiotics was significantly greater in direct inguinal hernia (n = 19/193; 9.8%) cases compared with that in total thyroidectomy (n = 4/152; 2.6%) and laparoscopic cholecystectomy (n = 2/251; 0.8%) cases; P = 0.001. Compliance to the timing was only 51% (n = 304/596) of the total patients received PAP which was significantly lower in GH 97/300 (32.3%) as compared with that in PH 207/296 (69.9%); P = 0.001. Administration timing of antibiotics was observed to be more appropriate in total thyroidectomy (n = 79/152; 51.9%) cases than in laparoscopic cholecystectomy (n = 130/251; 51.8%) and direct inguinal hernia (n = 95/193; 49.2%) cases; P = 0.001. The route and dose were appropriate in accordance with the guidelines in all cases (100%). Most of the patients received ceftriaxone, a third-generation cephalosporin that is no longer recommended by the latest international guidelines. The current analysis revealed an alarmingly poor adherence rate with the guidelines in the three elective surgical procedures at both hospitals. To improve the situation, training and awareness programs about the antimicrobial stewardship interventions on the institutional level may be valuable.

Polysaccharides, due to their outstanding properties, have attracted the attention of researchers, working in the biomedical field and especially of those working in drug delivery. Modified/functionalized polysaccharides further increase the importance for various applications. Delivery of therapeutics for diverse ailments in different endocrine glands and hormones safely, is a focal point of researchers working in the field. Among the routes followed, the transdermal route is preferred due to non‐exposure of active moieties to the harsh gastric environment and first‐pass metabolism. This review starts with the overview of polysaccharides used for the delivery of various therapeutic agents. Advantages of polysaccharides used in the transdermal route are addressed in detail. Types of polysaccharides will be elaborated through examples, and in this context, special emphasis will be on the polysaccharides being used for synthesis of the membranes/films. Techniques employed for their modification to design novel carriers for therapeutics delivery will also be discussed. The review will end with a brief discussion on recent developments and future perspectives for delivery of therapeutic agents, and vaccine development. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the utilization pattern of Surgical antibiotic prophylaxis (SAP) for the prevention of surgical infections in most common abdominal and orthopedic surgical procedures. Methods: A prospective observational and non-intervention study was conducted at two teaching hospitals (PIMS and SIH) in Islamabad, Pakistan. Prescriptions records were reviewed to assess the utilization pattern of SAP during the nine-month duration. Data regarding most common surgical procedures, antimicrobial utilization, dose, route and administration timing of SAP were extracted for analysis. Observed practices were compared with standard treatment guidelines. Results: Out of total 1512 surgical procedures about, 56.9% (n=860) of patients performed abdominal followed by 652 (43.1%) orthopedic surgical procedures. A total of 212 (14%) surgical procedures were completely correct in all steps. SAP were given in 1474 (97.5%) of surgical procedures. In 712 of the participants (48.3%) were given Ceftriaxone following by Cefazolin (n=247, 16.7%). Abdominal surgeries were majorly managed with Ceftriaxone (59%) while the orthopedic surgeries managed with Ceftriaxone (31.3%) and Cefazolin (30%). Appropriate choice of SAP was observed in (n=275; 18.6%) procedures and about half (n=719, 49%) received antibiotics within optimal timing. The appropriate choice/selection of SAP according to the guidelines was greater in orthopedic surgical procedures (n=212; 14.8%) than abdominal surgeries (n=63; 4.3%); p=0.001. Compliance with respect to timing was significantly lower in an orthopedic surgical procedure (n=301) as compared to abdominal surgeries (n=418); p=0.001. Similarly, a statistically significant difference observed between PIMS and SIH with respect to SAP practices; p=0.001. Conclusions: Inappropriate choice, the timing of administration and combination of SAP were observed in the current study. [ABSTRACT FROM AUTHOR]

Outage performance of a device-to-device (D2D) communication system in the presence of co-channel interference (CCI) is analyzed in this paper. Channels for the D2D and CCI signals are assumed to be κ-µ shadowed faded. Maximal ratio combining (MRC) and selection combining (SC) techniques are considered to combat fading conditions. Characteristic function (CF) expression of the D2D system in the presence of CCI is presented. Outage probability and success probability expressions are presented for the MRC and SC schemes. These outage probability and success probability expressions are functions of various CCI, path-loss and channel fading parameters. With the help of numerical results, effects of CCI on the performance of D2D communication system under different channel fading and path-loss conditions are discussed. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the outage probability, channel capacity and symbol error rate (SER) performance of device-to-device (D2D) communication systems. The D2D communication system is affected by several co-channel interferers. Gamma fading channel is considered for the D2D communication system. The channel for the co-channel interference is assumed to be Nakagami faded. An expression for the probability density function (PDF) of the signal-tointerference ratio (SIR) is presented. The PDF is a function of distances between various devices in the D2D system, path-loss, channel fading conditions and signal powers. Based on the PDF expression, we present the expressions for the outage, channel capacity and SER. With the help of numerical results the performance of D2D communication system is discussed under various conditions of interference, path-loss and channel fading. [ABSTRACT FROM AUTHOR]

Controlled release dosage forms provide sustained therapeutics effects for prolonged period of time and improve patient compliance. In present study, controlled release co-precipitates of Metoprolol Tartrate and Losartan Potassium were prepared by solvent evaporation method using polymers such as Eudragit RL 100 and Carbopol 974PNF and controlled release tablets were directly compressed into tablets. In-vitro dissolution of controlled release coprecipitates were performed by USP Method-II (paddle method) and tablets were evaluated by USP Method-I (rotating basket method) in phosphate buffer (PH 6.8) using pharma test dissolution apparatus. The temperature was maintained constant at 37±1.0 0C and the rotation speed of paddle and basket was kept constant at 100rpm. Drug release mechanisms were determined by applying Power Law kinetic model. The difference and similarity of dissolution profiles test formulations with reference standards were also determined by applying difference factor (f1) and similarity factor (f2). The results showed that the controlled release co-precipitates with polymer Eudragit RL 100 of both the drug extended the drug release rates for 10 hours and those having polymer Carbopol 974P NF extended the drug release rates for 12 hours. The controlled release tablets prepared from controlled release co-precipitates extended the drugs release up to 24 hours with both the polymers. The drug was released by all tests anomalous non fickian mechanism except F1 and F5 do not follow Power Law. The f1 and f2 values obtained were not in acceptable limits except F15 whose values were in acceptable limits. It is concluded from the present study that polymers (Eudragit RL 100 and Carbopol 974P NF) can be efficiently used in development of controlled release dosage forms having predictable kinetics. [ABSTRACT FROM AUTHOR]

Arsenic is a major threat to large part of the population due to its carcinogenic nature. The toxicity of Arsenic varies with its chemical form and oxidation states. Glutathione (GSH), a major intra-cellular tripeptide plays a major role in arsenic detoxification. The present study was designed to provide insight into the extent of changes in GSH level by inorganic arsenic in the form of Arsenic trioxide (ATO) and organic arsenic in the form of nitro benzene arsenic acid (NBA). Lymphocytes (T.cells and B.cells) were investigated for determination of change in GSH metabolic status caused by arsenic. The depletion of GSH level positively correlated with increasing arsenic concentration and time of incubation. The decline in GSH level was consistent with increasing pH and physiological temperature. Our findings show that changes in GSH status produced by Arsenic could be due to adduct (As-(SG)3) formation. This change in GSH metabolic status provides information regarding mechanism of toxicity of inorganic and organic arsenicals. These findings are important for the rational design of antidote for the prevention of arsenic induced toxicity. [ABSTRACT FROM AUTHOR]

Barium has important role in the field of medical sciences, but it has been found in various studies that barium can cause numerous toxic effects. Studies have proven the strong affinity of the metalloelements for the sulfhydryl group (SH), present in reduced glutathione (GSH) and other biological molecules. In this context, the study about the possible interaction of BaCl2 with glutathione in whole blood components was of interest, as an indication about the extent of barium toxicity and the role of glutathione in the conjugation and detoxification of the metalloelement barium. The concentration dependent and time dependent effect of BaCl2 on the level of GSH in plasma and Cytosolic Fraction in whole blood was investigated, following Ellman's method. It was found that BaCl2 causes a decrease in the GSH level, which is more pronounced with increasing concentration of BaCl2 and with time incubation as well. The observed effect GSH concentration may be presumably due to production of oxidized glutathione (GSSG) or then due to Barium- Glutathione (GS-Ba-SG) conjugate formation. [ABSTRACT FROM AUTHOR]

Metallo-elements including Vanadium (V) have strong affinity for sulfhydryl (-SH) groups in biological molecules including Glutathione (GSH) in tissues. Because of this fact it was of interest to further investigate the interaction of Ammonium Vanadate [NH4VO3] with Glutathione as a biomarker of toxicity and the role of Glutathione in the detoxification and conjugation processes in whole blood components including plasma and cytosolic fraction. Effects of different concentrations of Ammonium Vanadate [NH4VO3] on the level of reduced Glutathione in whole blood components (Plasma and Cytosolic fraction) were examined. GSH depletion in plasma and cytosolic fraction was Ammonium Vanadate's concentration-dependent. Depleted GSH level was more pronounced with more incubation time period. These findings show that changes in the GSH status produced by Ammonium Vanadate could be due to either by adduct formation of Vanadium and glutathione i.e. (V-SG) or by increased production of oxidized Glutathione (2GSH +V+5 → GSSG). This change in GSH metabolic status provides some information regarding the mechanism of toxicity by Ammonium Vanadate and the protective role of glutathione. [ABSTRACT FROM AUTHOR]

Being controlled release dosage forms, tablets allow an improved absorption and release profiles of Ofloxacin. The fact that drugs with fine particles size can be compressed well after wetting, so in our research studies Ofloxacin controlled release matrix tablets were prepared by wet granulation technique. In order to investigate the potential of Ethyl cellulose ether derivatives as a matrix material, Ofloxacin formulations with different types and grades of Ethocel were prepared at several drug-to-polymer ratios. The method adopted for in vitro drug release studies was USP Method-1 (rotating Basket Method) by Pharma test dissolution apparatus using phosphate buffer 7.4 pH as a dissolution medium. Various Kinetic models were employed to the formulations for the purpose of determination of release mechanism. A comparative study was performed between the tested Ofloxacin-Ethocel formulations and a standard reference obtained from the local market. F1 dissimilarity factor and f2 similarity factor were applied to the formulations for the checking of dissimilarities and similarities between the tested formulations and reference standard. [ABSTRACT FROM AUTHOR]

Functionalization, membranes/films, Natural Polysaccharides, polysaccharides in Endocrinology, polysaccharides in Vaccines Keywords: Functionalization; membranes/films; Natural Polysaccharides; polysaccharides in Endocrinology; polysaccharides in Vaccines EN Functionalization membranes/films Natural Polysaccharides polysaccharides in Endocrinology polysaccharides in Vaccines 1 1 1 06/12/21 20210610 NES 210610 B Polysaccharides b are an important element in several fields such as endocrinology, drug delivery, and vaccine. [Extracted from the article]

Background: Skin cancer has been the leading type of cancer worldwide. Melanoma and non-melanoma skin cancers are now the most common types of skin cancer that have been reached to epidemic proportion. Based on the rapid prevalence of skin cancers, and lack of efficient drug delivery systems, it is essential to surge the possible ways to prevent or cure the disease. Aim of review: Although surgical modalities and therapies have been made great progress in recent years, however, there is still an urgent need to alleviate its increased burden. Hence, understanding the precise pathophysiological signaling mechanisms and all other factors of such skin insults will be beneficial for the development of more efficient therapies. Key scientific concepts of review: In this review, we explained new understandings about onset and development of skin cancer and described its management via polymeric micro/nano carriers-based therapies, highlighting the current key bottlenecks and future prospective in this field. In therapeutic drug/gene delivery approaches, polymeric carriers-based system is the most promising strategy. This review discusses that how polymers have successfully been exploited for development of micro/nanosized systems for efficient delivery of anticancer genes and drugs overcoming all the barriers and limitations associated with available conventional therapies. In addition to drug/gene delivery, intelligent polymeric nanocarriers platforms have also been established for combination anticancer therapies including photodynamic and photothermal, and for theranostic applications. This portfolio of latest approaches could promote the blooming growth of research and their clinical availability.

Background: Multidrug-resistant tuberculosis (MDR-TB) is a growing public health problem. Treatment regimens used against MDR-TB are costly, prolonged, and associated with more side effects as compared with the drug-susceptible tuberculosis. This study was framed to determine the incidence of adverse drug events, risk factors, and their management in MDR-TB patients.Methods: This prospective follow-up cohort study was conducted at the site of programmatic management of drug-resistant TB located at the Pakistan Institute of Medical Sciences, Islamabad. All patients, irrespective of their age, gender, and ethnicity, were included in the study. Adverse drug events were observed in patients at different time points during the study. Patients enrolled for the treatment from January 2018 were prospectively followed till December 2020 up to their end treatment outcomes.Results: Out of 126 MDR-TB patients enrolled for treatment, 116 met the inclusion criteria and were included in the final analysis. Most patients (50.9%) were between 18 and 45 years of age. A minimum of one adverse event was experienced by (50.9%) patients. Of all the adverse events, gastrointestinal disorders were more frequent (47.4%), followed by arthralgia (28.4%) and psychiatric disturbance (20.6%). Furthermore, multivariate analysis showed a significant association with the incidence of adverse events in patients with age group above 60 years (odds ratio (OR) 4.50; 95% CI 1.05-19.2), active smokers (OR 4.20; 95% CI 1.31-13.4), delayed reporting to the TB center (OR 4.03; 95% CI 1.34-12.1), and treatment without bedaquiline regime (OR 3.54; 95% CI 1.23-10.1). Most of the patients (94.6%), counseled by the pharmacist, were found to be satisfied with the information provided and looked for more pharmacist counseling opportunities in the management of MDR-TB.Conclusion: Current findings recommend that ADEs might be well managed by timely identification and reporting. Bedaquiline coupled with other active medications lowered the chance of ADEs in MDR-TB patients. Elderly patients, active smoking behavior, and those who have a delay in the treatment initiation are more prone to ADEs. Clinical pharmacist’s contribution to TB control programs may help caregivers and patients concerning the rational use of medication, early detection, and management of ADEs.

Background: A judicious utilization of antibiotic prophylaxis and postoperative analgesics are an effective strategy to prevent surgical site infections and pain, respectively. Aims: The aim of this study was to assess prescription practices and guidelines adherence of antibiotics and analgesics in total knee replacement (TKR) surgery. Setting and Design: A cohort observational pilot study was conducted for a period of 2 months at two tertiary care teaching hospital (government hospital = GH and private hospital = PH) in Islamabad, Pakistan. Subjects and Methods: All the individuals aged ≥18 who underwent TKR surgery with no previous surgery and infection (n = 300) were included during the study period. The patient medication profile was analyzed through various indicators. International evidence-based guidelines were used as a reference to analyze current treatment practices. Statistical Analysis Used: Descriptive statistics such as frequencies, percentages, averages, standard deviation, and Chi-square test was used for interpretation of data in SPSS V-22.0. Results: Preoperative prophylactic antibiotics were prescribed in 94% (n = 283) cases. Of these, 61.5% adhered according to guidelines with respect to correct choice, 64.6% for timing, and 100% for the route (optimal value 100%). The prescribing behavior with respect to antibiotic choice and timing was different among GH and PH hospitals (P = 0.001). Cefazolin was the most commonly prescribed preoperative and postoperative antibiotic, followed by cefuroxime. With respect to analgesics, paracetamol and tramadol were frequently used in TKR patients. One hundred and seventy six (58.6%) patients received analgesics according to the guidlines recommendations, and 7.8% (n = 23) received more than one analgesic in their postoperative prescription. Conclusion: The low compliance rate with guidelines was observed. The choice and timing of antibiotic, selection of analgesics, and its multiple usage were main identified problems.

The present study aimed to fabricate and evaluate the therapeutic efficacy of pH-responsive Ibuprofen (IB) nanoparticles (NPs) loaded transdermal hydrogel against rheumatoid arthritis (RA). The IB loaded Eudragit® L 100 (EL 100) nanoparticles were formulated through a modified nanoprecipitation technique and optimized using central composite design software. The optimized NPs were loaded into Carbopol® 934-based hydrogel by solvent evaporation method and were analyzed for physicochemical characteristics. The mean particle size of the prepared NPs was 48 nm with an entrapment efficiency of 90%. The transdermal hydrogel showed a pH-responsive sustained drug release and high penetration through the skin. Moreover, the prepared nanocarrier system exhibited therapeutic efficacy at inflamed joints' sites both in acute and chronic RA mice model. The therapeutic efficacy of the prepared formulation was confirmed through the results of various behavioral, biochemical, and cytokines-based assays. Similarly, the assessment of histopathological and radiological images, as well as the skin irritation studies further strengthens the potential use of the prepared formulation through the transdermal route. The current findings suggested that IB loaded pH-responsive NPs based transdermal hydrogel can be used as an efficient agent to manage RA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The measurement of biological processes at a molecular and cellular level serves as a basis for molecular imaging. As compared with traditional imaging approaches, molecular imaging functions to probe molecular anomalies that are the basis of a disease rather than the evaluation of end results of these molecular changes. Proteases play central role in tumor invasion, angiogenesis and metastasis thus can be exploited as a target for imaging probes in early diagnosis and treatment of tumors. Molecular imaging of protease has undergone tremendous breakthroughs in the field of diagnosis. It allows the clinicians not only to see the tumor location but also provides an insight into the expression and activity of different types of markers associated with the tumor microenvironment. These imaging techniques are expected to have a huge impact on early cancer detection and personalized cancer treatment. Effective development of protease imaging probes with the highest in vivo biocompatibility, stability and most appropriate pharmacokinetics for clinical translation will upsurge the success level of early cancer detection and treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Methotrexate (MTX) is the first line agent for therapy against rheumatoid arthritis (RA); however, orally its efficacy is hampered by poor solubility, less permeability, short plasma half-life, and reduced bioavailability. Meanwhile, parenteral formulations are associated with severe adverse effects. In an attempt to improve the efficacy of MTX, we synthesized polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) triblock copolymer by a ring-opening copolymerization reaction and used it as a carrier for the fabrication of MTX-loaded nanomicelles. Surfactant-free, self-assembled nanomicelles were prepared by nanoprecipitation technique and optimized through central composite design. The optimized nanomicelles exhibited a size distribution of 31 nm and an encapsulation efficiency of 91%. In vitro, the nanomicelles exhibited hemocompatibility, sustained release, and significantly high uptake in lipopolysaccharide activated macrophages. To facilitate application on the skin, optimized nanomicelles were loaded into a Carbopol 934-based hydrogel with eucalyptus oil as a penetration enhancer. Eucalyptus oil significantly improved the permeation of nanomicelles through the skin ( p < 0.001). When the hydrogel was applied on the RA mice model, nanomicelles exhibited preferentially highest accumulation in the inflamed joints than other organs. As compared with the free MTX, MTX nanomicelles significantly improved the pharmacokinetic (4.34-fold greater half-life, 3.68-fold higher AUC 0- t , and 3.15-fold higher mean residence time) and pharmacodynamic profile ascertained through low inflammatory cytokines expression, improved oxidation protection, recovered behavioral responses, and radiological analysis. MTX nanomicelles-based hydrogel also significantly reduced the hepatotoxicity and did not activate the immune system. These results suggest that the MTX-loaded nanomicelles-based transdermal hydrogel can prove to be a promising agent against RA.

Nanotechnology has burgeoned over last decade exploring varieties of novel applications in all areas of science and technology. Utilisation of bio-friendly polymers for engineering nanostructures (NS) improves safety and efficacy in drug delivery. Biopolymers not merely employed for fabricating drug carriers but also leveraged for surface functionalisation of other NS to impart bio-mimicking properties. Biopolymer functionalised NS garnered researcher's attention because of their potential to enhance skin permeability of drug cargo. Biopolymers, i.e. cell-penetrating peptides (CPP), chitosan and hyaluronic acid not only enhance skin permeability but also add multiple functions due to their intrinsic biomimetic properties. This multifunctional drug delivery system is a promising tool to achieve skin delivery of large number of therapeutic agents. In this review, functionalisation of NS with biopolymers particularly polysaccharides and polypeptides is discussed in detail. In particular, applications of these functionalised NS for TDDS is elaborated. Moreover, this review provides framework for elaborating importance of functionalisation of NS to enhance skin permeability and depicts advantages of biopolymers to construct more biocompatible carriers for drug cargos.

Monocytes are leading component of the mononuclear phagocytic system that play a key role in phagocytosis and removal of several kinds of microbes from the body. Monocytes are bone marrow precursor cells that stay in the blood for a few days and migrate towards tissues where they differentiate into macrophages. Monocytes can be used as a carrier for delivery of active agents into tissues, where other carriers have no significant access. Targeting monocytes is possible both through passive and active targeting, the former one is simply achieved by enhanced permeation and retention effect while the later one by attachment of ligands on the surface of the lipid-based particulate system. Monocytes have many receptors e.g., mannose, scavenger, integrins, cluster of differentiation 14 (CD14) and cluster of differentiation 36 (CD36). The ligands used against these receptors are peptides, lectins, antibodies, glycolipids, and glycoproteins. This review encloses extensive introduction of monocytes as a suitable carrier system for drug delivery, the design of lipid-based carrier system, possible ways for delivery of therapeutics to monocytes, and the role of monocytes in the treatment of life compromising diseases such as cancer, inflammation, stroke, etc., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Silver nitrate (AgNO3) effect on the status of reduced glutathione (GSH), the major non-protein thiol in blood components were examined using freshly isolated plasma and cytosolic fraction of whole blood of healthy human volunteer. AgNO3 had significant effects on GSH contents reduction in plasma and cytosolic fraction of blood. Effect or reduction in GSH content was more pronounced or significant at AgNO3 concentration with time intervals (minutes to hours). Depletion of GSH in plasma and cytosolic fraction of blood by the addition of AgNO3 indicates that AgNO3 penetrated the cell membrane and reacted with GSH, depleted its contents mostly due to oxidation of reduced Glutathione (GSH) to glutathione disulphide (GSSG) 2 GSH-GSSG+2H+ or likely that AgNO3 after penetration formed a Silver-Glutathione (Ag-SG) complex. Time dependent effect of AgNO3 on the chemical status of glutathione was discussed in vitro in this paper which in principle presents the model of in vivo reaction, which will be the precise indirect impression of AgNO3 detoxification resulting by the interaction with GSH.