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OBJECTIVES: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel. METHODS: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed. RESULTS: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery. CONCLUSION: This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.
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Administración Cutánea , Antibacterianos , Cefepima , Quitosano , Geles , Tamaño de la Partícula , Absorción Cutánea , Piel , Quitosano/química , Cefepima/administración & dosificación , Cefepima/farmacocinética , Cefepima/química , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/química , Antibacterianos/farmacología , Geles/química , Animales , Absorción Cutánea/efectos de los fármacos , Piel/metabolismo , Ratas , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Pruebas de Sensibilidad Microbiana , Masculino , Portadores de Fármacos/química , Nanopartículas/química , Ratas WistarRESUMEN
OBJECTIVE: The main objective of this study was to develop a highly sensitive, accurate, and reproducible analytical method for the simultaneous detection of LEF and FA in polymeric nanocarriers. SIGNIFICANCE: Leflunomide (LEF), is widely employed in the treatment of rheumatoid arthritis (RA). However, long-term delivery of the drug is associated with systemic side effects. Therefore, folate (FA) conjugated LEF nanocarriers were fabricated for targeting the nanocarriers toward activated macrophages. HPLC is considered one of the most sensitive and precise analytical techniques for the simultaneous detection and estimation of different components in a particular sample. METHODS: Analysis was performed on HPLC (Shimadzu 10 A), having a reversed-phase C-18 column (Beckmen, 250 X 4.6 mm, 5 µm) equipped with a photodiode detector set at a wavelength of 260 nm (LEF) and 285 nm (Folic acid). The isocratic mobile phase was composed of acetonitrile, water, and trimethylamine in a ratio of 65:35:0.5 at pH 4. Rapid analysis of both agents was performed, with a total run time of 10 min (FA = 2.1 ± 0.1 min, LEF = 5.9 ± 1 min) at a 1 mL/min flow rate. RESULTS: The assay demonstrated good linearity of 0.9989 of 0.9997 for LEF and FA respectively with a recovery in the range of 95-100%. The method also depicted good specificity, and intra and inter-day precision based on relative standard deviation (RSD) values. CONCLUSIONS: The study concludes, that the developed method was helpful in the detection and quantitation of lower values of both agents from polymeric nanocarriers.
HighlightsOptimization and validation of the RP-HPLC method were performed for the simultaneous detection of LEF and FA.Validation was performed on the basis of linearity, accuracy, precision, LOD, LOQ, and robustness in accordance with ICH criteria.Validated analytical procedure was employed for the simultaneous detection of LEF and FA from polymeric nanocarriers.The proposed analytical method is reliable, fast, robust, and can be successfully applied for quantification of % EE, and % DL in polymeric nanocarriers.
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Ácido Fólico , Polímeros , Leflunamida , Cromatografía Líquida de Alta Presión/métodos , Reproducibilidad de los Resultados , Preparaciones FarmacéuticasRESUMEN
BACKGROUND: Adherence to standard guidelines is imperative when question comes to disease management. The present study aimed to evaluate the administration of adjunctive vitamin D therapy in various diseases, its adherence to standard guideline and the effect of socioeconomic status on the consumption of vitamin D in children. METHODS: Cross sectional observational study was conducted among 400 ambulatory pediatric patients at Children's Hospital, Pakistan Institute of Medical Sciences Islamabad, from November 2017 to June 2018. Data were collected by a self-designed structured questionnaire from the patient's medical chart. Adjunctive vitamin D therapy adherence was evaluated by the U. S endocrinology clinical practice guideline of vitamin D deficiency. The association between socioeconomic status and consumption of vitamin D was examined by chi-square. Alpha value (p ≤ 0.005) was considered statistically significant. Statistical analysis was done by SPSS version 25. RESULTS: In 400 patients, 9 diseases and 21 comorbid conditions were identified, in which adjunctive vitamin D therapy was prescribed. Adherence to vitamin D testing in high-risk vitamin D deficiency diseases as; seizures (3.8%), bone deformities (13.3%), steroid-resistant nephrotic syndrome (0.0%), cerebral palsy (5.9%) and meningitis (14.3%). Adherence to prescribed vitamin D dose was in (41.3%) patients in various diseases. Significant association (p < 0.05) was found between socioeconomic status and consumption of vitamin D in children and mothers. CONCLUSIONS: It was found that adjunctive vitamin D was being prescribed in various diseases and comorbidities. Overall poor adherence to the standard guideline was observed in disease management in children. Low socioeconomic status affects vitamin D supplementation consumption in children.
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Deficiencia de Vitamina D , Vitamina D , Niño , Estudios Transversales , Suplementos Dietéticos , Humanos , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/tratamiento farmacológico , Vitaminas/uso terapéuticoRESUMEN
This study was conducted to explore the frequency of positivity of cutaneous leishmaniasis (CL) in the tribal district Bajaur located near the Pak-Afghan border. The present study was conducted at the Leishmaniasis Center of Headquarter Hospital Khar District Bajaur, Pakistan. In total, 646 patients were recruited and included in the study after ethical approval and consent from the patients. CL was confirmed by taking blood samples from the sides of the lesion and observing them under a microscope using Giemsa staining. Information about demographic factors was collected from the study participants with a questionnaire and analyzed by SPSS. It was found that 73.8% of suspected patients were positive and 26.2% were negative for CL. There were 51.9% male and 48.1% female patients. The most frequently affected site was the face (42.6%), and most of the patients (85.8%) had only one lesion. The positivity of CL was higher among those under age 15 years. The area of most positivity, with 45.2% of the cases, was Tehsil Mamund. Most of the patients (46.6%) lived in stone houses, with 98.6% of patients having domestic animals in their houses. Approximately 198 patients were treated with intramuscular and intralesional injections of meglumine antimoniate, and their weekly follow-up revealed that 48% of patients recovered, while the remaining patients left the course of treatment at different stages of therapy. The positivity of CL is high in this area and is confirmed by the detection of Leishmania amastigotes in the blood collected from their lesions. Socioeconomic factors are the main underlying causes of the rapid spread of this disease and meglumine antimoniate is an effective drug.
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Antiprotozoarios , Leishmaniasis Cutánea , Compuestos Organometálicos , Adolescente , Animales , Antiprotozoarios/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/epidemiología , Masculino , Meglumina/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Pakistán/epidemiologíaRESUMEN
This study aimed to develop and optimise a Curcumin-loaded SLNs (C-SLNs) patch through a new approach for transdermal delivery. C-SLNs were optimised through the response surface central composite design using the modified injection method. Optimised C-SLNs were loaded into a polyvinyl alcohol-based patch through the backing membrane method. Compatibility studies (FTIR, XRPD), in vitro release, ex vivo skin permeation, accelerated stability, and evaluation studies of the patch were also performed. Prepared C-SLNs exhibited average particle diameter of 170 ± 2 nm with an encapsulation efficiency of 90 ± 3.5% (w/w) while SEM illustrated spherical shape of particles. In vitro release data ensured a sustained release for up to 72 hours. The enhancement ratio of C-SLNs based patch with permeation enhancer (PE) was high up to 6.5 folds as compared to patch without PE. It is concluded that the modified injection method is simple, economical, and less time consuming for the development of C-SLNs patch for the transdermal route.
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Curcumina/administración & dosificación , Sistemas de Liberación de Medicamentos , Lípidos/administración & dosificación , Nanopartículas , Administración Cutánea , Animales , Ratones , Tamaño de la Partícula , Permeabilidad , Difracción de Polvo , Absorción Cutánea , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
OBJECTIVE: This study was aimed to investigate TB patients adherence and treatment outcomes among internally displaced patients in comparison with adjacent settled areas. METHODS: The study was designed as an observational cross-sectional study among the TB patients of internally displaced populations (IDPs) of North Waziristan Agency (NWA) and adjacent settled areas of Bannu and Lakki Marwat (NIDPs). Based on the study inclusion and exclusion criteria 330 patients fullfilled the inclusion criteria and were assigned equally to both IDPs and NIDPs study groups. Odds ratio (OR) with 95% confidence interval was calculated and p-values, 0.05 were considered statistically significant. RESULTS: The treatment outcomes with the status of "cured" and "completed treatment" were better among NIDPs as compared to IDPs. Patients with treatment outcome status of "defaulted treatment", "without documentary evidence, and "failure" were high in IDPs as compared to NIDPs. Adherence to TB treatment was better among NIDPs (50.9%) as compared to IDPs (39.4%). The patients showing non-adherence to TB treatment were more among IDPS (27.3%) than NIDPs (10.9%). CONCLUSION: Overall results of this study revealed a poor adherence to the TB treatment medications with an odds ratio of 0.286, (p<0.05) among IDPs as compared with NIDPs.
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AIM: This study aimed to utilise the proficient function of diacerein (DCR) and anti-inflammatory polymers to develop sustained release nanoencapsulated emulgel for potential use in osteoarthritis (OA). METHODS: Chitosan (CHS) and chondroitin sulphate (CS) were employed as natural anti-inflammatory polymers to encapsulate nanoformulation of DCR. Optimised nanoformulation was prepared and characterised by investigating impact of polymers and surfactant on particle size, PDI, and encapsulation efficiency (EE). Afterwards, nanoemulgel of optimised DCR-NPs was formulated and evaluated for transdermal application. RESULTS: Optimised nanoformulation depicted spherical shape with particle size of 320 nm having PDI and EE of 0.3 ± 0.07 and 82 ± 4% (w/w), respectively. DCR-nanoemulgel depicts sustained action of drug up to 96 h with enhanced permeation activity and non-irritancy index. CONCLUSIONS: The elaborated nanoemulgel sustained release of drug having superior penetration properties with provision of enhanced therapeutic effect owing to the presence of CHS, CS, and Argan oil possessing indelible anti-inflammatory attributes.
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Antraquinonas/química , Biomimética , Quitosano/química , Nanopartículas/química , Osteoartritis/tratamiento farmacológico , Polímeros/química , Administración Oral , Animales , Antiinflamatorios/química , Sistemas de Liberación de Medicamentos , Diseño de Fármacos , Geles , Técnicas In Vitro , Masculino , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Piel/efectos de los fármacos , Espectroscopía Infrarroja por Transformada de Fourier , ViscosidadRESUMEN
Biodegradable materials are extensively employed to design nanocarriers that mimic extracellular environment in arthritis. The aim of this study was to formulate and characterize biocompatible, biodegradable ketoprofen-loaded chitosan-chondroitin sulfate (CHS-CS) nanoparticles with natural ingredients for transdermal applications. Polymers used in the design of nanocarriers are biodegradable and produce synergistic anti-inflammatory effect for the treatment of arthritis. For transdermal application, argan oil-based emulgel is utilized to impart viscosity to the formulation. Furthermore, naturally occurring argan oil synergizes anti-inflammatory effect of formulation and promotes skin penetration. CHS and CS form nanoparticles by polyelectrolyte complex formation or complex coacervation at pH 5.0. These particles were loaded into argan oil-based emulgel. Employing this method, nanoparticles were formulated with particle size in the range of 300-500 nm. These nanocarriers entrapped ketoprofen and showed more than 76% encapsulation efficiency and 77% release of the ketoprofen at pH 7.4 within 72 h. Drug releases from CHS-CS nanoparticles by mechanism of simple diffusion. Nanoparticle-loaded argan oil emulgel significantly enhanced skin penetration of ketoprofen as compared to marketed gel (p < 0.05). Nanocarriers prepared successfully delivered drug through transdermal route using natural ingredients. Graphical abstract á .
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Portadores de Fármacos/metabolismo , Cetoprofeno/metabolismo , Nanopartículas/metabolismo , Piel/metabolismo , Administración Cutánea , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/metabolismo , Quitosano/administración & dosificación , Quitosano/química , Quitosano/metabolismo , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Cetoprofeno/administración & dosificación , Cetoprofeno/química , Ratones , Nanopartículas/administración & dosificación , Nanopartículas/química , Tamaño de la Partícula , Polímeros/administración & dosificación , Polímeros/química , Polímeros/metabolismo , Piel/efectos de los fármacos , Absorción Cutánea/efectos de los fármacos , Absorción Cutánea/fisiologíaRESUMEN
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.
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Arseniatos/toxicidad , Intoxicación por Arsénico/metabolismo , Linfocitos B/efectos de los fármacos , Glutatión/metabolismo , Óxidos/toxicidad , Linfocitos T/efectos de los fármacos , Trióxido de Arsénico , Arsenicales , Linfocitos B/metabolismo , Humanos , Linfocitos T/metabolismoRESUMEN
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.
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Sortilin-related vacuolar protein sorting 10 (VPS10) domain containing receptor 3 (SORCS3) is a neuron-specific transmembrane protein involved in the trafficking of proteins between intracellular vesicles and the plasma membrane. Genetic variation at SORCS3 is associated with multiple neuropsychiatric disorders and behavioural phenotypes. Here, we undertake a systematic search of published genome-wide association studies to identify and catalogue associations between SORCS3 and brain-related disorders and traits. We also generate a SORCS3 gene-set based on protein-protein interactions and investigate the contribution of this gene-set to the heritability of these phenotypes and its overlap with synaptic biology. Analysis of association signals at SORSC3 showed individual SNPs to be associated with multiple neuropsychiatric and neurodevelopmental brain-related disorders and traits that have an impact on the experience of feeling, emotion or mood or cognitive function, while multiple LD-independent SNPs were associated with the same phenotypes. Across these SNPs, alleles associated with the more favourable outcomes for each phenotype (e.g., decreased risk of neuropsychiatric illness) were associated with increased expression of the SORCS3 gene. The SORCS3 gene-set was enriched for heritability contributing to schizophrenia (SCZ), bipolar disorder (BPD), intelligence (IQ) and education attainment (EA). Eleven genes from the SORCS3 gene-set were associated with more than one of these phenotypes at the genome-wide level, with RBFOX1 associated with SCZ, IQ and EA. Functional annotation revealed that the SORCS3 gene-set is enriched for multiple ontologies related to the structure and function of synapses. Overall, we find many independent association signals at SORCS3 with brain-related disorders and traits, with the effect possibly mediated by reduced gene expression, resulting in a negative impact on synaptic function.
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Encefalopatías , Estudio de Asociación del Genoma Completo , Proteínas del Tejido Nervioso , Receptores de Superficie Celular , Humanos , Encéfalo/metabolismo , Encefalopatías/metabolismo , Proteínas del Tejido Nervioso/genética , Fenotipo , Polimorfismo de Nucleótido Simple , Receptores de Superficie Celular/genéticaRESUMEN
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 ß [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.
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This study aims to determine UV-B resistance and to investigate computational analysis and antioxidant potential of methoxy-flavones of Micromonospora aurantiaca TMC-15 isolated from Thal Desert, Pakistan. The cellular extract was purified through solid-phase extraction and UV-Vis spectrum analysis indicated absorption peaks at λmax 250 nm, 343 nm, and 380 nm that revealed the presence of methoxy-flavones named eupatilin and 5-hydroxyauranetin. The flavones were evaluated for their antioxidant as well as protein and lipid peroxidation inhibition potential using di(phenyl)-(2,4,6-trinitrophenyl) iminoazanium (DPPH), 2,4-dinitrophenyl hydrazine (DNPH), and thiobarbituric acid reactive substances (TBARS) assays, respectively. The methoxy-flavones were further studied for their docking affinity and interaction dynamics to determine their structural and energetic properties at the atomic level. The antioxidant potential, protein, and lipid oxidation inhibition and DNA damage preventive abilities were correlated as predicted by computational analysis. The eupatilin and 5-hydroxyauranetin binding potential to their targeted proteins 1N8Q and 1OG5 is - 4.1 and - 7.5 kcal/mol, respectively. Moreover, the eupatiline and 5-hydroxyauranetin complexes illustrate van der Waals contacts and strong hydrogen bonds to their respective enzymes target. Both in vitro studies and computational analysis results revealed that methoxy-flavones of Micromonospora aurantiaca TMC-15 can be used against radiation-mediated oxidative damages due to its kosmotrophic nature. The demonstration of good antioxidant activities not only protect DNA but also protein and lipid oxidation and therefore could be a good candidate in radioprotective drugs and as sunscreen due to its kosmotropic nature.
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Flavonas , Micromonospora , Flavonas/farmacología , Antioxidantes/farmacología , LípidosRESUMEN
The aim of the study was to formulate and evaluate topically applied ketoprofen gels and patches and to see the effect of naturally occurring almond oil as penetration enhancer on the penetration of ketoprofen through artificial membrane/rabbit skin. Prior to ketoprofen gel and patch formulation, the particle size and particle size determination of ketoprofen was analyzed by Particle size analyzer (Horiba LA300). Ketoprofen gels and patches were formulated and almond oil was added in several concentrations i.e. 0.5%, 1%, 1.5%, 2%, 2.5% and 3%. The formulated gels were evaluated by several parameters like pH, spreadibility, consistency, homogeneity, skin irritation and drug content determination. In vitro drug permeation studies from transdermal gels and patches were carried out across artificial membrane and rabbit skin by using Franz Cell Apparatus (PermeGear, USA). Kinetics model was employed to the release patterns of ketoprofen from gel and patches in order to investigate the drug transport mechanism. The cumulative amount of drug penetrated from different formulations was statistically evaluated by using One-way analysis of variance (ANOVA). Stability study was performed for various batches of ketoprofen transdermal gel. Almond oil as penetration enhancer in various concentrations significantly enhances the penetration of drug from transdermal gels and patch across synthetic membrane/rabbit skin but was most significant when used in 3% concentration.
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Antiinflamatorios no Esteroideos/farmacocinética , Química Farmacéutica/métodos , Cetoprofeno/farmacocinética , Aceites de Plantas/farmacología , Piel/metabolismo , Parche Transdérmico/efectos adversos , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/química , Estabilidad de Medicamentos , Geles/administración & dosificación , Geles/efectos adversos , Geles/química , Cetoprofeno/administración & dosificación , Cetoprofeno/efectos adversos , Cetoprofeno/química , Tamaño de la Partícula , Conejos , Piel/efectos de los fármacos , Absorción Cutánea/efectos de los fármacosRESUMEN
Rapid progress in developing multifunctional nanocarriers for drug delivery has been observed in recent years. Inorganic mesoporous silica nanocarriers (MSNs), emerged as an ideal candidate for gene/drug delivery with distinctive morphological features. These ordered carriers of porous nature have gained unique attention due to their distinctive features. Moreover, transformation can be made to these nanocarriers in terms of pores size, pores volume, and particle size by altering specific parameters during synthesis. These ordered porous materials have earned special attention as a drug carrier for treating multiple diseases. Herein, we highlight the strategies employed in synthesizing and functionalizing these versatile nanocarriers. In addition, the various factors that influence their sizes and morphological features were also discussed. The article also summarizes the recent advancements and strategies for drug and gene delivery by rendering smarter MSNs by incorporating functional groups on their surfaces. Averting off-target effects through various capping strategies is a massive milestone for the induction of stimuli-responsive nanocarriers that brings out a great revolution in the biomedical field.
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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.
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The spread of drug-resistant tuberculosis (DR TB) poses significant challenges to the control and successful eradication of TB globally. The current retrospective study was designed to evaluate the treatment outcomes and identify the risk factors associated with unsuccessful outcomes among DR TB patients. A total of 277/308 eligible DR TB patients were enrolled for treatment at the programmatic management unit of DR TB at the Pakistan Institute of Medical Sciences, Islamabad between January 2014 and July 2019. Treatment outcomes were defined according to the WHO recommendations. Death, treatment failure, and lost to follow-up (LTFU) were collectively grouped as unsuccessful treatment outcomes, whereas cured and treatment completed were summed up together as successful treatment outcomes. Out of the total 277 patients, 265 (95.67%) were multidrug/rifampicin-resistant TB (MDR/RR-TB) cases, 8 (2.89%) were isoniazid resistant cases, and 4 (1.44%) were extensively drug-resistant ones. In the current cohort, a total of 177 (63.9%) achieved successful treatment outcomes. Among them, 153 (55.2%) were declared cured and 24 (8.7%) completed their treatment. Of the remaining 100 (36.1%) patients with unsuccessful outcomes, 60 (21.7%) died, 32 (11.5%) were LTFU, and 8 (2.9%) had failed treatment. The proportion of male patients was relatively higher (55.2%), within the age group of 21-40 years (47.3%) and lived in rural areas (66.8%). The multivariate analysis revealed that unsuccessful outcomes had a statistically significant association with being male (adjusted odds ratio, AOR: 1.92, 95% confidence interval (CI): 1.10-3.36), being in an age group above 60 years (AOR: 3.34, 95% CI: 1.09-10.1), suffering from any comorbidity (AOR: 2.69, 95% CI: 1.35-5.38), and the history of use of second-line drugs (AOR; 3.51, 95% CI 1.35-9.12). In conclusion, treatment outcomes among DR TB patients at the study site were poor and did not achieve the treatment success target (≥75%) set by the World Health Organization.
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Antituberculosos , Tuberculosis Resistente a Múltiples Medicamentos , Adulto , Antituberculosos/uso terapéutico , Humanos , Isoniazida/uso terapéutico , Masculino , Persona de Mediana Edad , Pakistán/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Adulto JovenRESUMEN
Background: Antibiotics misuse is a global challenge, and the situation is likely to deteriorate in conflict zones with insufficient health services. The misuse of antibiotics is not only associated with antimicrobial resistance but may also lead to serious consequences. This study was aimed to investigate the knowledge, attitude, and practices on antibiotic consumption, antibiotic resistance (ABR), and related suggestions among residents of conflicted zones in Pakistan. Methods: Semi-structured interviews were conducted at community pharmacies between June 2020 and January 2021. The primary findings were ascertained through thematic content analysis. Themes, sub-themes, and categories were drawn from the final analysis. Data analysis was carried out in six steps from getting to know the data to final report development. Results: A total of 20 consumers were interviewed with a mean interview duration of 25.4 min. The average age of participants was 35.1 years, and most of them were males. ABR was unfamiliar to the participants. Most of the participants understood the term "antibiotics," but they did not know how to use them properly. The participants were unable to distinguish between bacterial and viral illnesses. Thirteen participants believed that antibiotics have a faster effect than any other drug. Most of the participants perceived that every antibiotic could cause diarrhea, and pharmacy staff sometimes prefer other medicines such as multivitamins. Consumer practices regarding antibiotic usage and ABR were found to be poor. Most participants recommended that health officials must ensure qualified staff at pharmacies with strict regulations. Five participants said that a leaflet with antibiotic instructions in Urdu (national language) is usually beneficial, especially when making solutions from powder. Conclusions: This study underscored poor knowledge, attitude, and practices among residents of conflicted zones towards antibiotics and ABR. Low literacy rate, unavailability of healthcare facilities, absence of pharmacists at community pharmacies, and uncontrolled sales of antibiotics are some factors attributed to serious hazards, ABR, and irrational use of drugs.
RESUMEN
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.
Asunto(s)
Nanoestructuras , Neoplasias Cutáneas , Biología , Sistemas de Liberación de Medicamentos , Humanos , Nanoestructuras/química , Polietilenglicoles/química , Polímeros/química , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
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.