Development, optimization and evaluation of solid lipid nanoparticles of Celecoxib.

BACKGROUND: As indicated by the biopharmaceutical classification system, Celecoxib is a class II moiety. Many endeavors have been made to improve its solubility and consequently its dissolution rate, thus enhancing its overall bioavailability. In the present investigation, the nano-lipid technology was exploited to control the release of celecoxib (CXB) to overcome its dissolution problem. Solid lipid nanoparticles (SLNs) have a small particle size (50-1000 nm) that results in a large surface area-to-volume ratio, which further enhances the contact between the drug and the dissolution medium. This leads to improved drug release and absorption. Moreover, SLNs can solubilize hydrophobic drugs within the lipid matrix, increasing their effective solubility and facilitating their dissolution in an aqueous environment. AIM AND OBJECTIVE: The objective of the study was to enhance the solubility and bioavailability of a BCS Class-II drug-celecoxib formulating it as solid lipid nanoparticles. In order to overcome all its limitations, solid lipid nanoparticles of Celecoxib were developed, optimized, and evaluated for in-vitro and in-vivo parameters. METHODS: The CXB loaded-SLNs were prepared by solvent emulsification-diffusion technique. SLN was characterized using Fourier transform infra spectroscopy (FTIR) and evaluated for entrapment efficiency, drug loading, particle size, Polydispersity index (PDI), zeta potential, In-vitro release studies as well as in- vivoanti-inflammatory studies using rat paw edema method. The SLN formulations were optimized by central composite design (Design Expert 11- trial version). RESULTS: On the basis of outcomes of CCD the optimized formulation OF1 was selected as a desirable formulation. Its particle size, PDI, and zeta potential were found to be 314 nm, 0.204, and -18.73 respectively. It exhibited high entrapment efficiency (79±0.18 %) and drug loading (44.38±0.21 %). In-vitro release studies of the optimized formulation displayed the Korsemeyer-Peppas model with a maximum drug release of 89.42 ±0.12 % in 24 h. In-vivo studies also revealed that OF1 formulation reduced the rat paw volume to a minimum (1±0.32) in 24 h when compared to pure API (2±0.62) and marketed preparation (2±0.42). CONCLUSION: The results revealed that in-vitro release studies of optimized formulation exhibited a sustained drug release delivery. In-vivo anti-inflammatory studies proved that the CXB-loaded SLNs enhance the oral bioavailability more than pure API.

A Review on Autism Spectrum Disorder: Pathogenesis, Biomarkers, Pharmacological and Non-Pharmacological Interventions.

Autistic spectrum disorder (ASD) is a complicated developmental disease characterized by persistent difficulties in social interaction, speech and nonverbal communication, and restricted/ repetitive activities. Our goal is to deliver a step ahead awareness on neurodevelopment in ASD through early behavioral screenings, genetic testing, and detection of various environmental triggers. This would significantly reduce the tally of people with autistic characteristics. As of now, much work is to be done in understanding and treating ASD. Firstly, awareness campaigns must be organized and maintained so that ASD children can be identified and treated feasibly. Secondly, prenatal and prepregnancy environmental risk awareness, including advice against consanguineous marriages, information on optimum mother nutrition, and minimizing pollutants exposure, can be focused. Finally, the extension of genetic screening along with early postnatal monitoring of newborn feeding, nutrition, and eye contact will help in early therapy. People with ASD have strict dietary habits, but they are also more prone to gastrointestinal problems, including diarrhoea, constipation, and sometimes irritable bowel syndrome. Despite significant studies on the symptoms and possible causes of ASD, GI dysfunction is becoming a hot issue of discussion. Dietary strategies can partially help to alleviate both GI and behavioural issues due to the link between gut-microbiota and brain activity. Dietary treatments may be less expensive, easier to administer and have fewer adverse effects than pharmacological interventions. Hence, there is an increasing interest in autistic children's customized diets and supplements. Future studies should look at whether these diets are applicable to diverse people and whether they are practical in various circumstances (areas with fewer resources, lower socioeconomic areas, countries with different dietary restrictions, etc.). The dietary phytochemicals, including curcumin, resveratrol, naringenin, and sulforaphane, have a substantial role as neurotherapeutic agents. These agents can act as an antioxidant, immunomodulator, gut microbiota modulator and Nrf2 activator to provide benefits to ASD patients. Hence an urgent need is to create brain-targeted delivery methods for these dietary phytochemicals and to investigate their therapeutic value in ASD.

Evaluation of Ameliorative Effect of Quercetin and Candesartan in Doxorubicin-Induced Cardiotoxicity.

Background: Several mechanisms have been explored for the anthracycline myocardial toxicity. These are free-radical generation, myocyte apoptosis, lipid peroxidation, mitochondrial deterioration, and direct repression of muscle-specific gene expression. Adriamycin (Doxorubicin) is a potent anti-cancer agent. Adriamycin in prolonged use is fatal and generates free radicals that lead to dose-dependent cardiac toxicity. Objective: The intent of the study was to explore the protective activity of candesartan and quercetin in cardiomyopathy induced by doxorubicin in rats. Methods: To induce cardiac toxicity, rats were intraperitoneally treated with doxorubicin (06 equivalent injections of 2.5 mg/kg, i. p. at 48 hour interval for 02 consecutive weeks to achieve a cumulative dose of 15 mg/kg). Individual and combined oral treatment of candesartan (5 mg/kg/day) and quercetin (10 mg/kg/day) was administered for four weeks. Results: Following cardiomyopathy, heart/body weight ratio (3.526 × 10-3), serum creatine kinase (352.4±16.99 IU/L), lactate dehydrogenase (661.7±20.45 IU/L) levels were elevated in addition to altered lipid profile (TC - 118.4±4.25 mg/dL, TG - 263.3±9.99 mg/dL, VLDL - 52.66±1.99 mg/dL, LDL - 52.99±5.80 mg/dL and HDL - 12.78±0.36 mg/dL). The pre-cotreatment of candesartan and quercetin significantly restored the values to normal. The increased level of lipid peroxides (33.12±1.63 µmol/mg protein), serum troponin-T (1.82 ± 0.11 pg/mL) and nitric oxide (13.33±0.73 nmol/mg protein) level along with attenuating antioxidant profile, ie catalase, glutathione and superoxide dismutase (1.43±0.12 nmol/mg protein, 8.48±0.42 nmol/mg protein and 2.09±0.031 U/mg protein) were reversed to normal. Morphometry and histopathologic changes represented a beneficial effect of single and combination pre-cotreatment of drugs which significantly decreases adriamycin cardiac toxicity. Conclusion: The overall result depicts more beneficial and cardioprotective effect of quercetin and candesartan combination as compared to their individual effects in doxorubicin treated animals. Therefore, this combination might be a suitable option to treat the cardiotoxic effect of doxorubicin.