An insight to ocular in situ gelling systems

Eye is delicate organ of body whose defence mechanism restricts entry of exogenous substances. Conventional drug delivery systems get washed off within a short period of time and results in poor ocular bioavailability. Development of in situ gel having protracted ocular residence time is one of the mile stone triumphs by pharmaceutical researcher for treatment of eye aliments. This polymeric system showed sol-to-gel phase transition by change in physiological parameters in pre-corneal area which includes pH, temperature or ionic interactions etc. Three types of in situ gels are well known based on mechanism involved in phase transition viz. temperature dependent, pH sensitive, ion activated systems. Gel formed after phase transitions have high viscosity along with bio-adhesive property, which increases resistance for instantaneous rinse off due to defence contrivance. Plus it prevents nasal-lachrymal drainage and avoids the systemic side effects. Recently, in situ gels have been vexed in amalgamation with another drug delivery system. It may include use of two or more stimuli systems together or added advantages of nano-technology. Combination of in situ gel with nano-particles is utmost remedy for ocular treatment with water insoluble drugs

ENHANCEMENT OF TRANSCORNEAL PERMEATION AND SUSTAIN RELEASE OF TIMOLOL MALEATE FROM DEVELOPED AND OPTIMIZED IN SITU GEL WITH BETTER SAFETY PROFILE

Glaucoma is a chronic disease that causes irreversible blindness. Timolol Maleate is used as first line drug in treatment of glaucoma. Poor ocular bioavailability and therapeutic response shown by conventional ophthalmic system can be overcome by use of in situ gelling system which undergoes reversible sol to gel transition in cul-de-sac by physical stimulation. Present work describes formulation and evaluation of pH sensitive in situ gel system of Timolol Maleate. Carbopol 974P was used as pH sensitive polymer with HPMC K15M as viscosity modifier. 32 factorial design was used to study the effect of independent variables viz. concentrations of Carbopol 974P and HPMC K15M on dependent variables like in vitro drug diffusion and viscosity. Optimized batch showed 88.48% drug diffusion upto 8h. Optimized formulation was evaluated for various parameters such as drug release study, isotonicity, texture analysis, preservative efficacy studies, sterility testing as per IP 2010, accelerated stability studies. Ex vivo transcorneal permeability study was carried out on goat eye cornea which showed that EDTA (0.5%) increases drug penetration by 1.90 fold and showed no corneal damage after histological study. In conclusion, prepared formulation is stable and non-irritant

Targeting breast cancer using phytoconstituents: Nanomedicine-based drug delivery

Background: One of the most prevalent cancers in women worldwide is breast cancer. Breast cancer therapy is preferable to prevention. Breast cancer occurs for a variety of molecular reasons, making chemotherapy and/or radiotherapy treatment highly difficult and frequently creating unfavorable side effects. For millennia, practically every disease has been treated using plant extracts, and breast cancer is no exception. Because of their minimal toxicity, herbal medications are reliable for the treatment of cancer. In addition, the majority of breast cancer-stricken women readily embrace herbal treatments due to their accessibility and affordability. Many plants and the chemicals found in them have been found to exhibit promising anticancer properties versus breast cancer cells in both in vivo and in vitro studies over the past ten years. The poor stability, water solubility, and bioavailability of natural products usually prevent the clinical translation of these drugs, despite the positive preclinical outcomes. There have been efforts to get beyond these restrictions, especially by using nano-based drug delivery methods (NDDSs). The present work aims to comprehensively review the formulation, challenges, and advantages in the development of Nano formulation of Phytoconstituents for Breast Cancer. Main text: This study focuses on the tumor-targeting mechanisms of NDDSs, the benefits, and drawbacks of the main classes of NDDSs for treating breast cancer, as well as the pathophysiology of breast cancer, modern treatments, and phytoconstituents that have shown promise in treating breast cancer. Conclusion: The current review gathered information on the latest treatments, advantages, and disadvantages of NDDS in Breast Cancer. The review also elaborates on the importance of developing of a Targeted delivery system of Phytoconstituents for Breast Cancer

Extraction of rutin from tagetes erecta (Marigold) and preparation of peroral nano-suspension for effective antitussive/expectorant therapy

The present study narrates the extraction of rutin from Tagetes erecta (Marigold) via maceration followed by ultrasonication. The extracted rutin was further fabricated into nanoparticles by high-pressure homogenization (HPH) and assessed by HPLC, DSC, XRD, TEM, and FTIR spectroscopy. The optimized batch of nanoparticles obtained using 32 central composite design (CCD) which exhibited particle size 209±14 nm, PDI 0.234±0.06, and 92±1.3% entrapment efficiency. The lyophilized rutin nanoparticles were further converted into nano-suspension. Interestingly, the rutin nano-suspension exhibited a similar antitussive effect in vivo as that by standard treatment pentoxyverine and reduced the coughing times within 2 min. Also, the phlegm showed high UV absorbance, implying its better expectorant activity than the standard and control. The rutin nano-suspension was highly stable and shelf life was found to be ∼29.1 months. The present study, for the first time, paves a way for the use of rutin nano-suspension to overcome chest congestion, shortening of breath, and in the management of cough

Atorvastatin ascorbic acid cocrystal strategy to improve the safety and efficacy of atorvastatin

The study was aimed to investigate the effect of dissolution enhancement on the hypolipidemic effect and hepatotoxicity of the drug in hyperlipidemic rats. Atorvastatin ascorbic acid cocrystals were prepared by phase solution methods and characterized by Fourier transformation infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, X-Ray powder diffraction. Results of characterization confirmed that atorvastatin ascorbic acid cocrystals exhibited particle size was 221 nm. In in vitro study, results of dissolution test showed that the release of atorvastatin was increased to 1.6 folds. From In vivo study results, it was observed that in atorvastatin ascorbic acid cocrystals treated rats, serum total cholesterol, triglycerides, liver transaminase levels were significantly decreased, and liver glutathione activity was increased. In conclusion, atorvastatin ascorbic acid cocrystals therapy exhibited less hepatotoxicity in presence of ascorbic acid when compared to atorvastatin alone therapy and also the efficacy of therapy was improved

Atorvastatin ascorbic acid cocrystal strategy to improve the safety and efficacy of atorvastatin

The study was aimed to investigate the effect of dissolution enhancement on the hypolipidemic effect and hepatotoxicity of the drug in hyperlipidemic rats. Atorvastatin ascorbic acid cocrystals were prepared by phase solution methods and characterized by Fourier transformation infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, X-Ray powder diffraction. Results of characterization confirmed that atorvastatin ascorbic acid cocrystals exhibited particle size was 221 nm. In in vitro study, results of dissolution test showed that the release of atorvastatin was increased to 1.6 folds. From In vivo study results, it was observed that in atorvastatin ascorbic acid cocrystals treated rats, serum total cholesterol, triglycerides, liver transaminase levels were significantly decreased, and liver glutathione activity was increased. In conclusion, atorvastatin ascorbic acid cocrystals therapy exhibited less hepatotoxicity in presence of ascorbic acid when compared to atorvastatin alone therapy and also the efficacy of therapy was improved

Fabrication of nanoparticulate system for oral delivery of Naringenin against paraquat-induced Parkinson's disorder in Wistar rats

Background: Parkinson's disorder (PD) is a neurodegenerative condition associated with slow movement, tremors, imbalance, bradykinesia, and rigidity with advanced complications like sleep disorder, pains, sensory disability, and cognitive impairment. As per World Health Organization, PD is the leading neurological disorder worldwide. Although Parkinson's disorder cannot be cured, medications might significantly improve the symptoms. Current treatment for Parkinson's disorder includes cell implantation, Gene therapy, Surgical approaches, and Rehabilitation. But there are several adverse effects associated with these treatment methods which can be addressed using nanoparticles that possesses the ability to cross the blood-brain barrier, increased stability against enzymatic degradation, lowers liver toxicity, etc. Several Phyto-constituent have proven their role in the management of Parkinson's disorder. One such natural flavonoid is Naringenin, which is been reported to have diverse neuronal effects. Materials and methods: In the first part, the Naringenin-loaded PLGA nanoparticles were fabricated by using a single emulsion solvent emulsion method. Optimization was performed by using a 32-factorial design to investigate the impact of independent variables viz. PLGA concentration and number of HPH cycles. The optimized batch was spray-dried and evaluated for DSC, XRD, and SEM to confirm desired characteristics. LD50 was determine by performing Acute Oral Toxicity (AOT) study as per OECD-420 guidelines. Parkinson was induced by injecting rats with paraquat (i.p.) twice a week for 6 weeks. Simultaneously, nano-suspension and standard drug were also administered orally to respective group 60min prior to paraquat every day for 6 weeks. After 42/45 days parameters like Gross examination of the brain, Relative brain weight determination, behavioral parameters, biochemical evaluation (MDA, SOD, CAT, GSH, α-synuclein protein levels), and immunohistochemistry (BDNF level) investigation were performed. Brain histopathological study was performed to support the findings. Results: An optimized batch of Naringenin-loaded PLGA nanoparticles showed particle size, PDI, and %EE as 162.1 ​nm, 0.288, and 91% respectively. Spray-dried nanoparticles were found to be spherical during SEM analysis which may facilitate the easy movement of nanoparticles through different barriers. The DSC and XRD study confirmed the molecular dispersion of the drug. In vivo studies showed quite promising results through behavioural, histopathological, biochemical, and immunohistochemistry evaluations. Conclusions: In conclusion, Naringenin-loaded PLGA nanoparticles showed a protective effect on the levels of MDA, SOD, CAT, GSH, α- Synuclein protein, and BDNF and prevented the neurodegeneration in brain tissue in Paraquat-induced Parkinson's disorder. Based on the outcomes of present study, the use of Naringenin-loaded PLGA nanoparticle dispersion is the promising alternative available to Parkinson's disorder treatment