The next frontier in multiple sclerosis therapies: Current advances and evolving targets.

Recent advancements in research have significantly enhanced our comprehension of the intricate immune components that contribute to multiple sclerosis (MS) pathogenesis. By conducting an in-depth analysis of complex molecular interactions involved in the immunological cascade of the disease, researchers have successfully identified novel therapeutic targets, leading to the development of innovative therapies. Leveraging pioneering technologies in proteomics, genomics, and the assessment of environmental factors has expedited our understanding of the vulnerability and impact of these factors on the progression of MS. Furthermore, these advances have facilitated the detection of significant biomarkers for evaluating disease activity. By integrating these findings, researchers can design novel molecules to identify new targets, paving the way for improved treatments and enhanced patient care. Our review presents recent discoveries regarding the pathogenesis of MS, highlights their genetic implications, and proposes an insightful approach for engaging with newer therapeutic targets in effectively managing this debilitating condition.

Neuroprotective activity of Stereospermum suaveolens against global cerebral ischemia rat model.

CONTEXT: Stereospermum suaveolens DC. (Bignoniaceae) is a medicinal tree species native to India. Traditionally, the whole plant is used for various diseases including neuronal disorders. OBJECTIVE: The present study evaluated the neuroprotective activity of Stereospermum suaveolens against global cerebral ischemia in a rat model. MATERIALS AND METHODS: Neuroprotective activity was carried out by global cerebral ischemia on Sprague-Dawley rats and divided into five groups of eight rats each; sham and control groups received normal saline (10 ml/kg) and treated groups received methanol extract of Stereospermum suaveolens (MES) orally (125, 250, and 500 mg/kg) for 10 days prior to the experiment. Global cerebral ischemia was induced by bilateral carotid artery (BCA) occlusion for 30 min followed by 4-h reperfusion. The antioxidant enzymatic and non-enzymatic levels were estimated by UV spectroscopic method along with cerebral infarction area; histopathological studies were carried out. RESULTS: LD50 of MES was found to be 5000 mg/kg of body weight. The entire test was performed at dose levels 125, 250, and 500 mg/kg of body weight. The results of the study indicate that the Stereospermum suaveolens methanol extract showed neuroprotective activity by a significant decrease in lipid peroxidation (p < 0.001) and an increase in superoxide dismutase (p < 0.01), catalase (p < 0.01), glutathione (p < 0.001), and total thiol (p < 0.001) levels in extract-treated groups as compared to control group. Measurement of cerebral infarction area and histopathological studies further supported the protective effect of the extract. DISCUSSION AND CONCLUSION: These findings suggest a potential protective role of Stereospermum suaveolens against global cerebral ischemia/reperfusion-induced brain injury.

Potential nanocarrier-mediated miRNA-based therapy approaches for multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neuroinflammatory disorder attributed to neurodegeneration and demyelination, resulting in neurological impairment. miRNA has a significant role in biological processes in MS. In this review, we focus on the feasibility of delivering miRNAs through nanoformulations for managing MS. We provide a brief discussion of miRNA synthesis and evidence for miRNA dysregulation in MS. We also highlight formulation strategies and resulting technologies for the effective delivery of miRNAs through nanocarrier systems for achieving high therapeutic benefits.

Nomogram for computing the value of similarity factor.

The objective of present work was to construct nomogram for obtaining a value of similarity factor (f2) by employing the values of number of observations (n) and sum of squared difference of percentage drug dissolved between reference (R) and test (T) products . The steps for rearrangement of equation of similarity factor are presented. The values of f2 were selected in the range of 45 to 100 for 4 to 12 observations (n) for computing the values of Linear regression analysis was performed between number of observations and . Perfect correlation was observed in each case. Nomogram was constructed and later it was validated by using drug dissolution data from literature and our laboratory. The use of nomogram is recommended during research and development work to investigate effect of formulation or process variables. The nomogram can also be used during change in manufacturing site or change in equipment. It is concluded that the steps for calculation of f2 can be truncated in the middle (i.e. at the step of calculation of factor and a decision of similarity/dissimilarity can be taken employing the nomogram.

Neuroprotective activity of gossypin from Hibiscus vitifolius against global cerebral ischemia model in rats.

OBJECTIVES: The objective of this study is to evaluate the neuroprotective effect of gossypin (isolated from Hibiscus vitifolius) against global cerebral ischemia/reperfusion (I/R) injury-induced oxidative stress in rats. MATERIALS AND METHODS: Sprague Dawlet rats of wither gender were used in the study. Evaluation of cerbroprotective activity of bioflavonoid gossypin (in 5, 10 and 20 mg/kg oral doses) isolated from H. vitifolius was carried out by using the global cerebral I/R model by bilateral carotid artery occlusion for 30 min, followed by 24 h reperfusion. The antioxidant enzymatic and non-enzymatic levels were estimated along with histopathological studies. RESULT: Gossypin showed dose-dependent neuroprotective activity by significant decrease in lipid peroxidation (P < 0.001) and increase in the superoxide dismutase, catalase, glutathione and total thiol levels in gossypin treated groups when compared to control group. Cerebral infarction area was markedly reduced in gossypin treated groups when compared to control group. CONCLUSION: Gossypin showed potent neuroprotective activity against global cerebral I/R injury-induced oxidative stress in rats.

Formulation and evaluation of periodontal in situ gel.

BACKGROUND: The present study was aimed to develop and optimize in situ gel for the treatment of periodontal disease. MATERIALS AND METHODS: Temperature-sensitive in situ gel containing 0.1% w/v Chlorhexidine hydrochloride was formulated by cold method using different polymers. Preliminary study was carried out to optimize different types and concentration of polymers such as Poloxamer 188, Poloxamer 407, Gellan gum, and Carbopol 934P. Central composite design was employed for optimization of the effect of independent variables such as Poloxamer 407 and Carbopol 934P on responses such as gelation temperature, spreadability, cumulative percentage release at 2 h, and time for 50% drug release (t50 %). Each formulations were evaluated for clarity, pH, gelation temperature, spreadability, drug content, in vitro drug release, t50 %, and cumulative percentage drug release at 2 h. RESULTS: Results of evaluation parameters revealed that the drug release, gelation temperature was considerably decreased with increasing t50 % as the concentration of each polymer was increased. The desirability function was utilized to find out optimized formulation of the factorial design. Formulation F6 showed the highest overall desirability of 0.6283 and, therefore, this formulation was considered to be the optimized formulation. The % relative error was calculated, which showed that observed responses were in close agreement with the predicted values calculated from the generated regression equations. CONCLUSION: The clarity, pH, drug content of all formulations was found to be satisfactory. Further, all the formulations showed sustained drug release for a period of 6 h, which satisfied to treat periodontal disease.

Solid lipid nanoparticles of a water soluble drug, ciprofloxacin hydrochloride.

The aim of this study was to understand and investigate the relationship between experimental factors and their responses in the preparation of ciprofloxacin hydrochloride based solid lipid nanoparticles. A quadratic relationship was studied by developing central composite rotatable design. Amount of lipid and drug, stirring speed and stirring time were selected as experimental factors while particle size, zeta potential and drug entrapment were used as responses. Prior to the experimental design, a qualitative prescreening study was performed to check the effect of various solid lipids and their combinations. Results showed that changing the amount of lipid, stirring speed and stirring time had a noticeable influence on the entrapment efficiencies and particle size of the prepared solid lipid nanoparticles. The particle size of a solid lipid nanoparticle was in the range of 159-246 nm and drug encapsulation efficiencies were marginally improved by choosing a binary mixture of physically incompatible solid lipids. Release of ciprofloxacin hydrochloride from solid lipid nanoparticle was considerably slow, and it shows Higuchi matrix model as the best fitted model. Study of solid lipid nanoparticle suggested that the lipid based carrier system could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release for water soluble actives.

Neuroprotective activity of Stereospermum suaveolens DC against 6-OHDA induced Parkinson's disease model.

OBJECTIVES: To evaluate the neuroprotective effect of Stereospermum suaveolens DC on 6-hydroxy dopamine induced Parkinson's disease model. MATERIALS AND METHODS: The study was conducted on Sprague-Dawley rats where parkinson's disease was induced by producing the striatal 6-hydroxy dopamine lesions. The test animals received methanolic extract of Stereospermum suaveolens at dose of 125, 250 and 500 mg/kg for 42 days. Behavioral assessment, spontaneous locomotor activity and muscular coordination were studied. Antioxidant levels, striatal infraction area were assessed and histopathological studies were carried out. RESULTS: The Stereospermum suaveolens DC methanolic extract showed significant dose dependent increase in behavioral activity, improved muscular coordination. Significant reduction of lipid peroxidation (LPO), increased antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and non-enzymatic activity of glutathione (GSH) and total thiol levels in extract treated groups was observed in test groups as compared to control group. Striatal infarction area was significantly reduced in extract treated groups as compared to control group. CONCLUSION: The methanolic extract of Stereospermum suaveolens DC showed neuroprotective activity against 6-hydroxy dopamine induced Parkinson's disease in rats.

Exploration of Novel Co-processed Multifunctional Diluent for the Development of Tablet Dosage Form.

The aim of this investigation was to develop a novel multifunctional co-processed diluent consisting of microcrystalline cellulose (Avicel PH 102), crospovidone (Polyplasdone XL) and polyethylene glycol 4000. Colloidal silicon dioxide and talc were also incorporated as minor components in the diluent to improve tableting properties. Melt granulation was adopted for preparation of co-processed diluent. Percentage of Avicel PH 102, Polyplasdone XL and polyethylene glycol 4000 were selected as independent variables and disintegration time was chosen as a dependent variable in simplex lattice design. The co-processed diluent was characterised for angle of repose, bulk density, tapped density, Carr's index, percentage of fines and dilution potential study. Acetaminophen and metformin were used as poorly compressible model drugs for preparation of tablets. The blend of granules of drug and extra-granular co-processed diluent exhibited better flow as compared to the blend of drug granules and physical mixture of diluents blend. The diluent exhibited satisfactory tableting properties. The tablets exhibited fairly rapid drug release. In conclusion, melt granulation is proposed as a method of preparing co-processed diluent. The concept can be used to bypass patents on excipient manufacturing.