Physicochemical Evaluation and Pharmacological Screening of Fernando Adenophylla Steenis Fruits.

The current study aimed to evaluate the physicochemical properties of Fernandoa adenophylla. Powder studies were carried out to estimate the quantitative physicochemical characteristics of the crude drug, including moisture content, ash content, and extractive values. Using a Soxhlet apparatus and different analytical grade solvents, 3 sample extracts of a crude drug were made. To evaluate the potentially toxic nature, an acute oral toxicity study was performed as per OECD guideline no. 423. Sample extracts were tested and analyzed by ANOVA for pharmacological potential (analgesic, antipyretic, and antidiabetic) using Wister-Albino rats. Where physicochemical analysis indicated purity, quality, and presence of organic/inorganic materials in crude drug extracts, no sign of mortality was found up to 2000 mg/kg of body weight of Fernandoa adenophyllas extracts. Analgesic activity was observed in all sample extracts, whereas only chloroform and ethanolic extracts expressed antipyretic and antidiabetic potential. Ethanolic extract was found to be most potent in pharmacological potential as 200mg/kg extract dose exhibited %age pain inhibition of 55.12% and reduced body temperature from 39.78±0.03°C to 37.22±0.02°C in hyperthermic rats. A decrease in blood glucose levels up to 57.88% was observed on the 21st day of the treatment with 500mg/kg ethanolic extract.

Ethosomes: a potential nanovesicular carrier to enhancing the drug delivery against skin barriers.

Ethosomes, which are liposomes like structures, mainly composed primarily of ethanol, have attracted considerable attention due to their potential to enhance the drug permeation via skin. The article discusses the formulation and preparation methods of ethosomes, offering insights into the various factors that influence their size, shape, and stability. Moreover, it explores the techniques used to assess the physicochemical properties of ethosomes and their impact on drug delivery effectiveness. The article also elucidates the mechanism by which ethosomes enhance skin permeation, emphasising their ability to modify the lipid structure and fluidity of the stratum corneum. Additionally, the review investigates the applications of ethosomes in diverse drug delivery scenarios, including the delivery of small molecules, peptides, and phytoconstituents. It highlights the potential of ethosomes to improve drug bioavailability, extend drug release, and achieve targeted delivery to specific skin layers or underlying tissues.

Solid lipid nanoparticles: a versatile approach for controlled release and targeted drug delivery.

Solid Lipid Nanoparticles (SLN), the first type of lipid-based solid carrier systems in the nanometer range, were introduced as a replacement for liposomes. SLN are aqueous colloidal dispersions with solid biodegradable lipids as their matrix. SLN is produced using processes like solvent diffusion method and high-pressure homogenization, among others. Major benefits include regulated release, increased bioavailability, preservation of peptides and chemically labile compounds like retinol against degradation, cost-effective excipients, better drug integration, and a broad range of applications. Solid lipid nanoparticles can be administered via different routes, such as oral, parenteral, pulmonary, etc. SLN can be prepared by using high shear mixing as well as low shear mixing. The next generation of solid lipids, nanostructured lipid carriers (NLC), can reduce some of the drawbacks of SLN, such as its restricted capacity for drug loading and drug expulsion during storage. NLC are controlled nanostructured lipid particles that enhance drug loading. This review covers a brief introduction of solid lipid nanoparticles, manufacturing techniques, benefits, limitations, and their characterization tests.

Molecular markers for the detection of pathogenic and food poisoning potential of methicillin resistant Staphylococcus aureus isolated from wounds of hospitalized patients.

Pathogenic strains of Staphylococcus aureus are mostly resistant to methicillin and they can cause severe infections. The current study was planned to assess the food poisoning potential of pathogenic, methicillin resistant Staphylococcus aureus by molecular detection of enterotoxin A (Eta) gene. A total of 100 septic wound samples from patients admitted in surgical ward (n=50) and burn unit (n=50) of Mayo Hospital Lahore were collected aseptically. These samples were processed primarily for bacterial growth on nutrient agar and purified on mannitol salt agar where twenty (20) samples showed pin-point colonies with yellow discoloration of media. Moreover, isolates were further characterized on the basis of microscopic appearance and biochemical assays where fourteen (14) isolates were declared Staphylococcus. DNA of these isolates were subjected to 16S rRNA gene amplification and sequences of S. aureus were submitted to NCBI GenBank viz., MW344063.1, MW341438.1, MW344064.1, MW344065.1, MW341439.1, MW341440.1, MW345971.1, MW345972.1, MW345973.1, MW716458.1. All the isolates (n=10) demonstrated molecular confirmation of pathogenicity and methicillin resistance by amplification of Coa and mecA gene. Out of these ten isolates, three amplified enterotoxin A (Eta) gene were confirmed. It is concluded that enterotoxin A of S. aureus which causes food poisoning is present in pathogenic, methicillin resistant S. aureus isolated from various wounds infections.

Endogenous THBD (Thrombomodulin) Mediates Angiogenesis in the Ischemic Brain-Brief Report.

OBJECTIVE: THBD (thrombomodulin) is part of the anticoagulant protein C-system that acts at the endothelium and is involved in anti-inflammatory and barrier-stabilizing processes. A recombinant soluble form of THBD was shown to have protective effects in different organs, but how the endogenous THBD is regulated during ischemia, particularly in the brain is not known to date. The aim of this study was to investigate the role of THBD, especially in brain endothelial cells, during ischemic stroke. Approach and Results: To induce ischemic brain damage, we occluded the middle cerebral artery of mice. We found an increased endothelial expression of Thbd in the peri-infarct area, whereas in the core of the ischemic tissue Thbd expression was decreased compared with the contralateral side. We generated a novel Cre/loxP-based mouse line that allows for the inducible deletion of Thbd specifically in brain endothelial cells, which worsened stroke outcome 48 hours after middle cerebral artery occlusion. Unexpectedly, we found no signs of increased coagulation, thrombosis, or inflammation in the brain but decreased vessel diameters and impaired angiogenesis in the peri-infarct area that led to a reduced overall vessel length 1 week after stroke induction. CONCLUSIONS: Endogenous THBD acts as a protective factor in the brain during ischemic stroke and enhances vessel diameter and proliferation. These previously unknown properties of THBD could offer new opportunities to affect vessel function after ischemia and thereby improve stroke outcome.

Role of Adaptor Protein Myeloid Differentiation 88 (MyD88) in Post-Subarachnoid Hemorrhage Inflammation: A Systematic Review.

Myeloid differentiation 88 (MyD88) is a well-established inflammatory adaptor protein. It is one of the essential downstream proteins of the toll-like receptor 4 (TLR4) signaling pathway. TLRs are pattern recognition receptors that are usually activated by the damage-associated molecular pattern molecules (DAMPs). Sterile inflammation is triggered by the endogenous DAMPs released in response to global cerebral ischemia and from extravasated blood after subarachnoid hemorrhage (SAH). In this review, we highlight the importance of the neuroinflammatory role of the MyD88 in the SAH. We also explore a few possible pharmacological agents that can be used to decrease SAH-associated neuroinflammation by modulating the MyD88 dependent functions. Pharmacological agents such as flavonoids, melatonin, fluoxetine, pentoxifylline and progesterone have been investigated experimentally to reduce the SAH-associated inflammation. Inhibition of the MyD88 not only reduces the expression of pro-inflammatory cytokines, but also potentially inhibits other processes that can augment the SAH associated inflammation. Further investigations are required to translate these findings in the clinical setting.

Evaluation of cytokines expression in the phytoflavonoids treated epileptic rats: An in vivo study.

Seizure are basic characteristic of epilepsy; these initiate due to irregular, excessive and synchronous electrical discharges. We aimed to determine the antiepileptic potential of phyto-flavonoids on the evaluation of the mRNA expression of TNF-α, IL-6, IL-1 Beta, IL-10, IL-1Ra, IL 4 and NF-κB. We induced chronic epilepsy in rats by administering sub-convulsive dose of pentylenetetrazole (25 mg/kg/day for 28 days). We observed intensity and frequency of seizures. Levetiracetam was used as a standard drug and divided all the subjects into 6 groups. All experimental animals were trained to acclimatize the behaviour tests. Food and water intake, changes in the body weight and WBC levels were assessed. Using qPCR, we assessed mRNA expression levels of, TNF α, IL-6, IL1 beta, NF-κB, IL1Ra, IL-4, and IL-10. qPCR confirmed the down regulation of the pro- and up-regulation of the anti-inflammatory cytokines. Significant reduction in seizure frequency, neutrophil counts and improvement in behaviour were observed when compared treatment group to control groups. PF exerts their antiepileptic activity by the downregulation of pro- and upregulation of anti-inflammatory cytokines respectively.

Lauric acid: Its role in behavioral modulation, neuro-inflammatory and oxidative stress markers in haloperidol induced Parkinson's disease.

The study was designed to investigate the neuro-protection of lauric acid (LA) on haloperidol (HPD) induced Parkinson's disease (PkD) rat model. Rats were divided into group A (normal), group B (diseased, by HPD 1mg/kg i.p. for 14 days), group C (standard treatment, levodopa 30 mg/kg), group D (vehicle coconut oil 1ml/kg), group E (LA 0.66mg/kg) and group F (LA 1.32mg/kg) for 35 days after induction of PkD. The study displayed a state of oxidative stress in the striatum of rat model of PkD as shown from the increased MDA, NO levels and the decreased superoxide dismutase levels. HPD caused an increase in tumor necrosis factor-α level, NF-κB, IL-8 mRNA expression and suppress IL-4 expression. Neuro-protection with LA attenuated the oxidative stress and changes in pro-inflammatory cytokines induced due to PkD induction. The LA treatment also showed improvement in the histo-pathology of the rats' brain. LA also improved behavioral performances, food intake, weight gain as compared to animal of diseased group and prevented decline in motor activities (assessed Rotarod, and Beam walking test). LA showed significant neuro-protection against oxidative stress, inflammatory cytokines and behavioral changes in HPD induced rat model of PkD.

Patterns of physicians' knowledge, attitude and prescribing trends against upper respiratory tract infections in Lahore, Pakistan.

Although viruses cause most of upper respiratory tract infections but still antibiotics are irrationally prescribed in mild infections, especially in upper respiratory tract infections. To identify gaps among prescribers, due to lack of standard guidelines and antimicrobial stewardship programs, it is needed to check knowledge, attitude, perception and current prescribing pattern of antibiotics. Based on the data recommendations can be specified to overcome the prescribing deficiencies and increasing rates of antimicrobial resistance. It is inevitable to educate patients about ineffectiveness of antibiotics in viral infections, and to develop guidelines for prescribing antibiotics, running continuing medical education and establishing antibiotic stewardship programs. We conducted a cross-sectional survey-based study by engaging physicians of public and private sector hospitals in Lahore, Pakistan. About 66% agreed for semi-structured interview and met the inclusion criteria. Fifty percent of physicians have an understanding that antibiotics should be prescribed in URTIs, otherwise symptoms may get worsen. The only encouraging thing is that 78.8% believe that antibiotics are being misused and are major cause of increasing rate of resistance. Most of prescribers have an understanding that antibiotics should be prescribed in upper respiratory tract infections. They are prescribing antibiotics ignoring Center for Disease Control guidelines for the treatment or prophylaxis of upper respiratory infections.

Effectiveness of clobazam on perception, creativity, intelligence, selective and visual memory.

Clobazam belongs to benzodiazepine class and is preferably used against anti-epileptic disorders. However, when used in reduced doses, its ability for improving cognitive functions becomes explicitly evident. This study objectively undertook the task of using the reduced doses of clobazam for proving potentials effects on cognitive functions. The drug, clobazam was administered in "active group" which contained 15 young healthy volunteers. The "placebo group" also entailed 15 subjects and each was administered with placebo drug. The controlled group? also included 15 subjects. All these 45 young healthy subjects were subjected to tests for perceptual learning, creativity, selective memory, visual memory and intelligence. Results clearly demonstrated significant impact of clobazam at the dose of 5mg/day on perceptual learning (P=0.0380), creativity (P=0.0787), memory function (P=0.4920), visual memory (P=0.4816) and intelligence of the subject (P=0.4920). The outcomes highlighted in the studies reviled the positive effects of clobazam when used at reduced doses.

pH responsive alginate polymeric rafts for controlled drug release by using box behnken response surface design.

Aim of the present work was to develop alginate raft forming tablets for controlled release pantoprazole sodium sesquihydrate (PSS). Box behnken design was used to optimize 15 formulations with three independent and three dependent variables. Physical tests of all formulations were within pharmacopoeial limits. Raft was characterized by their strength, thickness, resilience, acid neutralizing capacity, floating lag time and total floating time. Raft strength, thickness and resilience of optimized formulation AR9 were 7.43 ± 0.019 g, 5.8 ± 0.245 cm and greater than 480 min, respectively. Buffering and neutralizing capacity were 11.2 ± 1.01 and 6.5 ± 0.56 meq, respectively. Dissolution studies were performed by using simulated gastric fluid pH 1.2 and cumulative percentage release of optimized formulation AR9 was found 98%. First order release kinetics were followed and non-fickian diffusion was observed as value of n was greater than 0.45 in korsmeyer-peppas model. PSS, polymers, tablets and rafts were further characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). FTIR spectra of PSS, polymers and raft of optimized formulation AR9 showed peaks at 3223.09, 1688.17, 1586.67, 1302.64 and 1027.74 cm-1 due to -OH stretching, ester carbonyl group (C=O) stretching, existence of water and carboxylic group in raft, C-N stretching and -OH bending vibration showed no interaction between them. XRD showed diffraction lines indicates crystalline nature of PSS. DSC thermogram showed endothermic peaks at 250 °C for PSS. The developed raft was suitable for controlled release delivery of PSS.

DEVELOPMENT AND EVALUATION OF IVABRADINE HCI-LOADED POLYMERIC MICROSPHERES PREPARED WITH EUDRAGIT L100-55 (METHACRYLIC ACID-ETHYL ACRYLATE COPOLYMER) AND ETHYL CELLULOSE FOR CONTROLLED DRUG RELEASE.

The objective of this study was to prepare and evaluate ivabradine HCl-loaded microspheres consisting of Eudragit LIOO-55 and ethyl cellulose prepared by oil-in-oil solvent evaporation method. Ivabradine HCl was encapsulated into microspheres by in situ method. The resultant microspheres were characterized with respect to drug loading, flow properties, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffractometry (XRD), thermal analysis and release behavior. Chemical stability of IBH after being encapsulated into microspheres was confirmed by FTR, DSC and XRD. FTIR spectra reflect- ed no interaction between drug and excipients. TGA indicates that prepared microspheres showed much better thermal stability than pure drug ivabradine. SEM images showed formulation of microspheres in spherical shape. The maximum perceniage entrapment efficiency was found to be 81 ± 2.15 and percentage yield was 88 ± 2.65. The maximum in vito drug release was 94.5% for the pH 7.4 and demonstrated that all drug-loaded formulations had a pH-dependent drug release. The cumulative drug release data were analyzed by applying different kinetic models. Korsmeyer-Peppas equation was used to determine value of n which follows non-Fickian diffusion.

Comparison of Pakistani CKD-EPI, new Asian-modified CKD-EPI and revised Lund-Malmö study equations in a South Asian CKD population: a study from a Pakistani CKD cohort.

BACKGROUND: Newly proposed estimating glomerular filtration rate equations need to be studied, evaluated and compared for chronic kidney disease staging, diagnosis and medication dosing in South Asians. The objectives of the study were (1) to assess the performance of the CKD-EPIPK, CKD-EPIAsian-Modified, and LMRevised equations in the Pakistani chronic kidney disease population, and (2) to investigate prospective implications on chronic kidney disease classification and end-stage kidney disease prevalence. METHODS: We conducted a cross-sectional analysis on a chronic kidney disease cohort of 385 participants 18 years of age or above. RESULTS: CKD-EPIPK showed the lowest bias (- 1.33 ml/min/1.73 m2), highest precision [IQR, 2.33 (- 2.36, - 0.03)] and enhanced P30 accuracy (89.35%) compared to the CKD-EPIAsian-Modified and LMRevised equations. The mean difference (ml/min/1.73 m2), 95% limit of agreement (ml/min/1.73 m2) of the equations were; CKD-EPIAsian-Modified: - 5.98, - 13.03, LMRevised: - 4.06, - 8.13 and CKD-EPIPK: - 1.18, - 6.14 (P < 0.001). CKD-EPIAsian-Modified and LMRevised showed upward re-classification of the GFR categories compared to the CKD-EPIPK equation except in the G5 category where the highest count (217, 56.36%) was noted for the CKD-EPIPK equation. End-stage kidney disease prevailed in all age groups according to all equations, and the prevalence was high in females in all equations. CONCLUSION: CKD-EPIPK showed the best performance, whereas both CKD-EPIAsian-Modified and LMRevised showed poor performance and did not offer a sufficient advantage in chronic kidney disease classification and end-stage kidney disease prevalence estimation over CKD-EPIPK. Hence, CKD-EPIPK seems ideal for South Asians, thus appropriate measures should be taken for its implementation, at least in Pakistani laboratories.

Comparison of EKFC, Pakistani CKD-EPI and 2021 Race-Free CKD-EPI creatinine equations in South Asian CKD population: A study from Pakistani CKD community cohort.

INTRODUCTION: South Asian individuals possess a high risk of chronic kidney disease. There is a need to study, evaluate, and compare the newly suggested glomerular filtration rate (eGFR) equations for accurate CKD diagnosis, staging, and drug dosing. This study aimed to (1) evaluate the European Kidney Function Consortium (EKFC), Pakistani CKD-EPI, and 2021 Race-Free CKD-EPI creatinine equation in the South Asian population with CKD and (2) to examine the expected implications on both CKD classification as well as End Stage Renal Disease (ESRD) prevalence across these equations in South Asian population. METHODS: We carried out a cross-sectional investigation on 385 participants, a CKD cohort ≥ 18 years, at Allama Iqbal Medical College, Jinnah Hospital, Lahore. Serum creatinine was measured by Jaffe's method and rGFR was measured by inulin clearance. RESULTS: Pakistani CKD-EPI has a lower median difference at -1.33 ml/min/1.73m2 elevated precision (IQR) at 2.33 (-2.36, -0.03) and higher P30 value at 89.35% than 2021 CKD-EPI and EKFC equations. The mean difference (ml/min/1.73m2), 95% agreement limits (ml/min/1.73m2) of CKD-EPI PK: -1.18, -6.14, 2021 CKD-EPI: -5.98, -13.24 and EKFC: -5.62, -13.01 (P <0.001). These equations highly correlated to rGFR (P <0.001). An upward re-classification in GFR categories was shown by 2021 CKD-EPI and EKFC compared to the Pakistani CKD-EPI equation. However, there was an exception regarding the G5 category, where an elevated count of 217 (56.36%) was shown for CKD-EPI PK. The prevalence of ESRD was seen in entire age groups and prevailed among females more than in males overall equations. CONCLUSIONS: Pakistani CKD-EPI exhibited outstanding performance, while 2021 CKD-EPI and EKFC demonstrated poor performances and could not show an adequate advantage for both CKD classification and prevalence of ESRD compared to Pakistani CKD-EPI. Therefore, Pakistani CKD-EPI appears optimal for this region and warrants future validation in other South Asian countries. In contrast, suitable measures must be implemented in Pakistani laboratories.

Nanoparticle-based Gene Therapy for Neurodegenerative Disorders.

Neurological disorders present a formidable challenge in modern medicine due to the intricate obstacles set for the brain and the multipart nature of genetic interventions. This review article delves into the promising realm of nanoparticle-based gene therapy as an innovative approach to addressing the intricacies of neurological disorders. Nanoparticles (NPs) provide a multipurpose podium for the conveyance of therapeutic genes, offering unique properties such as precise targeting, enhanced stability, and the potential to bypass blood-brain barrier (BBB) restrictions. This comprehensive exploration reviews the current state of nanoparticle-mediated gene therapy in neurological disorders, highlighting recent advancements and breakthroughs. The discussion encompasses the synthesis of nanoparticles from various materials and their conjugation to therapeutic genes, emphasizing the flexibility in design that contributes to specific tissue targeting. The abstract also addresses the low immunogenicity of these nanoparticles and their stability in circulation, critical factors for successful gene delivery. While the potential of NP-based gene therapy for neurological disorders is vast, challenges and gaps in knowledge persist. The lack of extensive clinical trials leaves questions about safety and potential side effects unanswered. Therefore, this abstract emphasizes the need for further research to validate the therapeutic applications of NP-mediated gene therapy and to address nanosafety concerns. In conclusion, nanoparticle-based gene therapy emerges as a promising avenue in the pursuit of effective treatments for neurological disorders. This abstract advocates for continued research efforts to bridge existing knowledge gaps, unlocking the full potential of this innovative approach and paving the way for transformative solutions in the realm of neurological health.

Chitin: A versatile biopolymer-based functional therapy for cartilage regeneration.

Chitin is the second most abundant biopolymer and its inherent biological characteristics make it ideal to use for tissue engineering. For many decades, its properties like non-toxicity, abundant availability, ease of modification, biodegradability, biocompatibility, and anti-microbial activity have made chitin an ideal biopolymer for drug delivery. Research studies have also shown many potential benefits of chitin in the formulation of functional therapy for cartilage regeneration. Chitin and its derivatives can be processed into 2D/3D scaffolds, hydrogels, films, exosomes, and nano-fibers, which make it a versatile and functional biopolymer in tissue engineering. Chitin is a biomimetic polymer that provides targeted delivery of mesenchymal stem cells, especially of chondrocytes at the injected donor sites to accelerate regeneration by enhancing cell proliferation and differentiation. Due to this property, chitin is considered an interesting polymer that has a high potential to provide targeted therapy in the regeneration of cartilage. Our paper presents an overview of the method of extraction, structure, properties, and functional role of this versatile biopolymer in tissue engineering, especially cartilage regeneration.

Smart integration of cold plasma stream and surface discharge with ns laser ablation for composite nanomaterial.

In this paper, smart integration of cold dielectric barrier discharge (DBD) plasma in various geometrical arrangements with laser ablation at atmospheric pressure for nanomaterial was described. A composite Co:ZnO target was ablated in an airflow by a nanosecond (ns) laser (wavelength: 1064 nm, pulse duration: 30 ns) using fluence of 5 J-cm-2 at a repetition rate of 10 Hz. The nanomaterial produced under vertical and oblique plasma streams, surface discharge and gas flow, were compared. Utilization surface discharge markedly improved the material adhesion by altering surface intrinsic behavior, inducing anticipated surface energy activation, chemical changes, and the formation of a densely packed solid structure. Under all conditions, the material consistently retained its crystalline nature, elemental composition, and ultraviolet emission characteristics. These preliminary findings hold promise for additional research, suggesting avenues for making complex materials in a flexible environment. Such new advancements could facilitate applications in the biomedical, catalysis, pharmaceutical, and surgical device domains.

Preparation and Evaluation of a Self-Emulsifying Drug Delivery System for Improving the Solubility and Permeability of Ticagrelor.

Ticagrelor (TCG) is a BCS class IV antiplatelet drug used to prevent platelet aggregation in patients with acute coronary syndrome, having poor solubility and permeability. The goal of this study was to develop a self-nanoemulsifying drug delivery system (SNEDDS) of TCG to improve its solubility and permeability. The excipients were selected based on the maximum solubility of TCG and observed by UV spectrophotometer. Different combinations of oil, surfactant, and co-surfactant (1:1, 2:1, and 3:1) were used to prepare TCG-SNEDDS formulations, and pseudo-ternary phase diagrams were plotted. The nanoemulsion region was observed. Clove oil (10-20%), Tween-80 (45-70%), and PEG-400 (20-45%) were used as an oil, surfactant, and co-surfactant, respectively. The selected formulations (F1, F2, F3, F4, F5, and F6) were analyzed for ζ potential, polydispersity index (PDI), ζ size, self-emulsification test, cloud point determination, thermodynamic studies, entrapment efficiency, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), in vitro dissolution, ex vivo permeation, and pharmacodynamic study. The TCG-SNEDDS formulations exhibited ζ potential from -9.92 to -6.23 mV, a ζ average of 11.85-260.4 nm, and good PDI. The in vitro drug release in phosphate buffer pH 6.8 from selected TCG-SNEDDS F4 was about 98.45%, and F6 was about 97.86%, displaying improved dissolution of TCG in 0.1 N HCl and phosphate buffer pH 6.8, in comparison to 28.05% of pure TCG suspension after 12 h. While the in vitro drug release in 0.1 N HCl from F4 was about 62.03%, F6 was about 73.57%, which is higher than 10.35% of the pure TCG suspension. In ex vivo permeability studies, F4 also exhibited an improved apparent permeability of 2.7 × 10-6versus 0.6708 × 10-6 cm2/s of pure drug suspension. The pharmacodynamic study in rabbits demonstrated enhanced antiplatelet activity from TCG-SNEDDS F4 compared to that from pure TCG suspension. These outcomes imply that the TCG-SNEDDS may serve as an effective means of enhancing TCG's antiplatelet activity by improving the solubility and permeability of TCG.

Lauric acid provides neuroprotection against oxidative stress in mouse model of hyperglycaemic stroke.

During ischemic stroke, higher glucose level linked worse outcomes were reported even in patients without pre-existing diabetes. Evidence suggest that such worse stroke outcomes were mainly due to production of reactive, toxic glucose metabolites that expands oxidative damage inside the brain. As a consequence of high oxidative stress, microvasculature structures and tight junctions compromised their functionally, infarct volume expands and brain edema exacerbates. In a mouse model of ischemic stroke with induced acute hyperglycaemia, Lauric acid (LA) as a natural saturated fatty acid demonstrated neuroprotection by attenuating infarct volume and brain edema. In addition, in the ipsilateral hyperglycaemic brain, the LA significantly increased the expression of tight junction representative protein (occludin) as well as anti-oxidative markers; Manganese superoxide dismutase (Mn) SOD, Extracellular superoxide dismutase (Ec-SOD) and nuclear factor-erythroid factor 2-related factor 2 (Nrf2) in the ipsilateral region against hyperglycemic ischemic stroke. LA treated animals showed a significant reduction in the production of lipid peroxidation products (4-HNE) in the microvascular structures, maintained the blood brain barrier (BBB) integrity. LA linked neuroprotective outcomes were further confirmed by behavioral tests, where functional outcomes and motor coordination were improved significantly. Furthermore, LA treatment enhanced food intake, decreased mortality rate, and net body weight loss. Conclusively, LA modulated ischemic insult exacerbated by hyperglycemia and provided neuroprotection.

Fabrication and Characterization of Celecoxib-Loaded Chitosan/Guar Gum-Based Hydrogel Beads.

The aim of this study was to fabricate celecoxib-loaded chitosan/guar gum (CS/GG) single (SC) and dual (DC) crosslinked hydrogel beads using the ionotropic gelation approach. The prepared formulations were evaluated for entrapment efficiency (EE%), loading efficiency (LE%), particle size and swelling studies. The performance efficiency was assessed by in vitro drug release, ex-vivo mucoadhesion, permeability, ex-in vivo swelling and in vivo anti-inflammatory studies. The EE% was found to be ~55% and ~44% for SC5 and DC5 beads, respectively. The LE% was ~11% and ~7% for SC5 and DC5 beads, respectively. The beads showed a matrix-like network with thick fibers. The particle size of beads ranged from ~2.74 to 1.91 mm. About 74% and 24% celecoxib was released from SC and DC hydrogel beads, respectively, within 24 h. The SC formulation showed higher %swelling and permeability than the DC counterpart, while the %mucoadhesion was relatively higher for DC beads. During the in vivo study, a significant decrease in the inflammation of the rat paw and inflammatory markers including C-reactive proteins (CRP) and interleukin-6 (IL-6) was observed following treatment with the prepared hydrogel beads; however, the SC formulation showed better therapeutic efficiency. In conclusion, celecoxib-loaded crosslinked CS/GG hydrogel beads can provide sustained drug release and act as potential candidates for managing inflammatory conditions.