SYNTHESIS AND CHARACTERIZATION OF THIOLATED JACKFRUIT SEED STARCH AS A COLONIC DRUG DELIVERY CARRIER

Objective: Site-specific drug delivery into the colonic region is extremely fascinating for local treatment of various colonic diseases like ulcerative colitis, colon cancer but it should be capable of saving the drug from hydrolysis and degradation. The present study reports the application of jackfruit seed starch and its thiol derivative as a drug delivery carrier for the colon. Methods: The starch was extracted from the jackfruit seeds by water extraction method and modified by the esterification reaction with thioglycolic acid. The thiolated starch was characterized for morphology, functional and flow properties. The safety profile of the thiolated starch was confirmed by acute toxicity study in a mice model as per OECD guidelines 423. The microspheres based on thiolated starch were prepared by ionic gelation method incorporating Ibuprofen as a model drug. The prepared microspheres were characterized for particle size, drug entrapment efficiency, drug loading, compatibility study, surface morphology, in vitro drug release and release kinetics. Results: The result attributed that starch was successfully modified by the thiolation with a degree of substitution of 3.30. The size of prepared microspheres ranges from 825.5±4.58 to 857±6.24 µm, the entrapment efficiencies ranges from 69.23±1.19 to 76.15±0.83 % and the drug loading capacity ranges from 17.75±0.30 to 46.05±0.49 %. The FT-IR, DSC and XRD studies confirmed that there is no interaction within drug and excipients. The thiolated starch microspheres show the maximum release of drug at pH 7.4 in the presence of rat caecal content as compared to pH 1.2 and pH 6.8 for up to 24 h and are following first order release kinetics. Conclusion: These results suggest the application of thiolated jackfruit seed starch could be promising as a long-term drug delivery carrier for the colon

BOOSTING THE SKIN DELIVERY OF CURCUMIN THROUGH STEARIC ACID-ETHYL CELLULOSE BLEND HYBRID NANOCARRIERS-BASED APPROACH FOR MITIGATING PSORIASIS

Objective: Curcumin presents poor topical bioavailability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of psoriasis. The present study reports the utilization of lipid-polymer hybrid nanoparticles (LPHNPs) for the topical delivery of curcumin which can be a potential approach for mitigating psoriasis. Methods: Curcumin-loaded LPHNPs were prepared by the emulsification solvent evaporation method and characterized. The optimized Curcumin-loaded LPHNPs (DLN-3) were further incorporated into 2% Carbopol 940 gels and evaluated for its therapeutic efficacy in the Imiquimod (IMQ)-induced psoriasis rat model. Results: The average particle size, polydispersity index, zeta potential, drug entrapment and loading efficiency for DLN-3 were found to be 200.9 nm, 0.342,-28.3 mV, 87.40±0.99% and 4.57±0.04%, respectively. FT-IR, DSC and XRD studies confirmed that all the components used for the formulation are compatible with each other, whereas SEM and TEM analysis affirmed the spherical shape of LPHNPs with a smooth surface. The in vitro drug release studies suggest that curcumin was released from the LPHNPs in a sustained manner over a period of 24 h via super case II transport mechanism. Results of in vitro skin permeation study revealed that 38.39±2.67% of curcumin permeated at 12 h across excised pig ear skin with a permeation flux of 18.74±3.59 µg/cm2/h. Further, in vivo evaluation and histopathological studies demonstrated that NLHG-1 hydrogels showed better therapeutic efficacy against the psoriatic skin lesions than the standard marketed gels. Conclusion: These results suggest that the developed LPHNPs have a superior ability to improve the skin penetration or accumulation of DLN-3 within psoriatic skin and offer a potential delivery system for the management of psoriasis

erbBGenes in the Mouse Uterus: Cell-Specific Signaling by Epidermal Growth Factor (EGF) Family of Growth Factors during Implantation

AbstractWe previously described spatiotemporal expression of various epidermal growth factor (EGF)-like ligands and receptor subtypes, ErbB1 and ErbB2, during the peri-implantation period. To better understand the roles of these ligands and their possible signaling schemes in implantation, it is important to define the status of all the ligands and receptor subtypes in the uterus/embryo. No information is available about uterine and embryonic status of ErbB3 or ErbB4 during implantation. We cloned mouseerbB3anderbB4cDNAs and examined their expression and bioactivity in the peri-implantation uterus (days 1–8). TwoerbB3(cytoplasmic and extracellular) and threeerbB4(two cytoplasmic and one extracellular) clones were generated. Both forms of theerbB3clone showed similar transcript profiles, while different transcript profiles were obtained witherbB4clones. The steady-state levels oferbB3anderbB4mRNAs in whole uterine poly(A)+RNA samples showed little changes during the peri-implantation period, while their unique cell-specific accumulation was noted.erbB3is predominantly expressed in the epithelial cells, although decidual and embryonic cells also accumulate this mRNA. In contrast, theerbB4mRNA is primarily expressed in the submyometrial stroma and myometrial connective tissues during this period. Additionally, the extracellular form of theerbB4clone detected signals in a subpopulation of stromal cells. Autophosphorylation and immunoprecipitation studies provided evidence that uterine ErbB3 and ErbB4 are biologically active. This study provides a comprehensive analysis of possible ligand–receptor signaling schemes for EGF-like ligands in implantation

BOX-BEHNKEN DESIGN APPROACH TO DEVELOP NANO-VESICULAR HERBAL GEL FOR THE MANAGEMENT OF SKIN CANCER IN EXPERIMENTAL ANIMAL MODEL

Objective: To manage the increasing burden of skin cancer cases globally and to replace conventional invasive treatments and their side effects, the present study is aimed to develop a transfersomal herbal gel of Green Tea Catechins (GTC) extracted from indigenous green tea and evaluate it for in vivo management of skin cancer in an experimental animal model. Methods: GTC-loaded transfersomes (GTCTF) were prepared by the thin-film hydration method. After optimizing the GTCTFs using the Box-Behnken design, they were characterized for zeta potential, structure, in vitro drug release, and in vitro skin permeation. Carbopol 940 gel was developed for the topical delivery of GTCTF and characterized for pH, viscosity, spreadability and in vitro skin permeation. In vitro MTT assay and in vivo chemopreventive and anticancer efficacy of the GTCTF gel were evaluated in mice. Results: The GTCTF has shown a particle size of 151.4±1.9 nm, entrapment efficiency of 68.25±0.06 %, and drug loading of 10.41±0.02 %. The in vitro MTT assay in B16F10 melanoma cell lines showed promising anticancer efficacy of the GTCTF. GTCTF gel was found suitable for topical delivery with favorable pH, viscosity, spreadability, and permeability and effective in preventing and curing skin cancer in mice, with a significant reduction of tissue biochemical parameters like TNF-α, IL-1β, and IL-6. Conclusion: Collectively, successful prevention and curing of the induced skin cancer in the experimental animal model by the GTCTF gel have established a novel herbal nanomedicine approach for the management of skin cancer

Season-wise length-weight relationship and relative condition factor of Tenualosa ilisha (Hamilton, 1822) at Narmada estuary, Gujarat, India

635-638Length-weight relationship and relative condition factor of T. ilisha was conducted for one year (2014-15) at Narmada estuary, Gujarat, India. Fish samples were collected from Bharuch, Bhadbhut, Mehgam and Ambetha landing sites covering 72 km of estuarine stretch. Two distinct fishing seasons were observed at Narmada estuary, viz., June-October and January-March, though the bulk of the harvest comes from monsoon season. A total of 312 fish samples were collected, 270 during monsoon and 42 during the winter season. The mean length and weight were recorded 35.37±11.36 cm and 625.83±39.81 g during monsoon and 36.84±3.82 cm and 537.44 ± 17.45 g during the winter season. The ‘b’ value was found to be 3.07 and 2.76 and relative condition factor was 1.02 and 1.01 during monsoon and winter seasons, respectively

Decidual Cell Polyploidization Necessitates Mitochondrial Activity

Cellular polyploidy has been widely reported in nature, yet its developmental mechanism and function remain poorly understood. In the present study, to better define the aspects of decidual cell polyploidy, we isolated pure polyploid and non-polyploid decidual cell populations from the in vivo decidual bed. Three independent RNA pools prepared for each population were then subjected to the Affymetrix gene chip analysis for the whole mouse genome transcripts. Our data revealed up-regulation of 1015 genes and down-regulation of 1207 genes in the polyploid populations, as compared to the non-polyploid group. Comparative RT-PCR and in situ hybridization results indeed confirmed differential expressional regulation of several genes between the two populations. Based on functional enrichment analyses, up-regulated polyploidy genes appeared to implicate several functions, which primarily include cell/nuclear division, ATP binding, metabolic process, and mitochondrial activity, whereas that of down-regulated genes primarily included apoptosis and immune processes. Further analyses of genes that are related to mitochondria and bi-nucleation showed differential and regional expression within the decidual bed, consistent with the pattern of polyploidy. Consistently, studies revealed a marked induction of mitochondrial mass and ATP production in polyploid cells. The inhibition of mitochondrial activity by various pharmacological inhibitors, as well as by gene-specific targeting using siRNA-mediated technology showed a dramatic attenuation of polyploidy and bi-nucleation development during in vitro stromal cell decidualization, suggesting mitochondria play a major role in positive regulation of decidual cell polyploidization. Collectively, analyses of unique polyploidy markers and molecular signaling networks may be useful to further characterize functional aspects of decidual cell polyploidy at the site of implantation

Clinical Predictors and Outcome of Metabolic Acidosis in Under-Five Children Admitted to an Urban Hospital in Bangladesh with Diarrhea and Pneumonia

BACKGROUND: Clinical features of metabolic acidosis and pneumonia frequently overlap in young diarrheal children, resulting in differentiation from each other very difficult. However, there is no published data on the predictors of metabolic acidosis in diarrheal children also having pneumonia. Our objective was to evaluate clinical predictors of metabolic acidosis in under-five diarrheal children with radiological pneumonia, and their outcome. METHODS: We prospectively enrolled all under-five children (n = 164) admitted to the Special Care Ward (SCW) of the Dhaka Hospital of icddr, b between September and December 2007 with diarrhea and radiological pneumonia who also had their total serum carbon-dioxide estimated. We compared the clinical features and outcome of children with radiological pneumonia and diarrhea with (n = 98) and without metabolic acidosis (n = 66). RESULTS: Children with metabolic acidosis more often had higher case-fatality (16% vs. 5%, p = 0.039) compared to those without metabolic acidosis on admission. In logistic regression analysis, after adjusting for potential confounders such as age of the patient, fever on admission, and severe wasting, the independent predictors of metabolic acidosis in under-five diarrheal children having pneumonia were clinical dehydration (OR 3.57, 95% CI 1.62-7.89, p = 0.002), and low systolic blood pressure even after full rehydration (OR 1.02, 95% CI 1.01-1.04, p = 0.005). Proportions of children with cough, respiratory rate/minute, lower chest wall indrawing, nasal flaring, head nodding, grunting respiration, and cyanosis were comparable (p>0.05) among the groups. CONCLUSION AND SIGNIFICANCE: Under-five diarrheal children with radiological pneumonia having metabolic acidosis had frequent fatal outcome than those without acidosis. Clinical dehydration and persistent systolic hypotension even after adequate rehydration were independent clinical predictors of metabolic acidosis among the children. However, metabolic acidosis in young diarrheal children had no impact on the diagnostic clinical features of radiological pneumonia which underscores the importance of early initiation of appropriate antibiotics to combat morbidity and deaths in such population