Formulation and development of colon-targeted mucopenetrating metronidazole nanoparticles

Purpose: To formulation and develop colon-targeted mucopenetrating metronidazole nanoparticles.Methods: Metronidazole-loaded chitosan nanoparticles with a pH-sensitive polymer, hydroxyl propyl methyl cellulose phthalate (HPMCP), were prepared by ionic gelation technique and then coated with Eudragit S100 by solvent evaporation method. The nanoparticles were optimized using one variable at a time (OVAT) approach. Further, the nanoparticles were evaluated by scanning electron microscopy (SEM) and zeta sizer, as well as for in-vitro release. Muco-adhesion was evaluated by modified bioadhesion detachment force measurement balance and muco-penetration of fluorescein isothiocyanate (FITC) labeled optimized nanoparticles was determined by microscopic techniqueResults: Morphological assessment results revealed smooth, spherical particles with homogeneous distribution and polydispersity index (PDI) of 0.213. The optimized formulation showed particle size of 202 ± 27 nm, zeta potential of 26.9 ± 2.4 mV as well as and entrapment efficiency of 79 ± 5.4 %. There was significant difference in drug release between coated (8.46 ± 2.49 %) and uncoated (28.96 ± 4.04%) nanoparticles at the 5th h in simulated gastric conditions. Muco-adhesion data revealed that uncoated nanoparticles (14.98 x 103 dyne/cm2) showed higher muco-adhesion detachment force compared to coated (12.34 x 103 dyne/cm2) nanoparticles. Muco-penetration results confirm the retention (for up to 12 h) of the developed formulation at the target site for enhanced therapeutic exposure of the entrapped drug.Conclusion: Eudragit S100 coating of chitosan-HPMCP nanoparticles promotes efficient drug targeting and thus provides a strategy for treating mucosal infections. .Keywords: Metronidazole, pH-sensitive nanoparticles, Hydroxylpropyl methylcellulose phthalate, Ionic gelation, Mucoadhesion, Mucopenetration, Intestinal infectio

NOVEL DRUG DELIVERY SYSTEMS: DESIRED FEAT FOR TUBERCULOSIS

Tuberculosis has claimed its victims throughout much of known human history and is currently the most devastating human bacterial disease. The ability to infect human population on a global scale, combined with the widespread emergence of multi-drug resistant strains, has led to the placement of Mycobacterium tuberculosis on the National Institute of Allergy and Infectious Diseases (NIAID) list of Biodefence and Emerging Infectious Disease Threats Agents. The resurgence of interest in tuberculosis (TB) has stemmed because of increased evidences from developed countries. Contrary to expectations, no country has reached the phase of elimination and in no subsection of society TB has been completely eliminated. A deeper understanding of the process will assist in the identification of the host and mycobacterial efforts involved and provide targets for therapeutic strategies against tuberculosis. The article presents a view on pathogenesis of tuberculosis and its diverse manifestations, host defense evasion, mechanisms of microbial persistence, emergence of Multiple Drug Resistance and Extensive Drug Resistance, conventional therapy used and the possible novel systems which are under extensive investigation as drug carriers for improving the cytosolic concentration of the anti-tubercular agents

Ethnic Differences in Trabecular Bone Score.

Trabecular bone score (TBS), a noninvasive textural analysis of the lumbar spine dual-energy X-ray absorptiometry (DXA) image, has been shown to predict fractures in Caucasian (CA) populations but has not been thoroughly studied in African-American (AA) populations. The aim of this study was to compare the TBS in AAs and CAs and to assess whether TBS can be used to refine fracture risk stratification in AA patients. Eight hundred twenty-five women (390 AAs, 435 CAs) referred for bone mineral density (BMD) as part of their clinical care had measurements of the TBS, the BMD of the lumbar spine, total hip, and femoral neck, and vertebral fracture assessment for detection of vertebral fractures. Unadjusted TBS was higher in CA than AA (1.275 vs 1.238, p < 0.001), but this was no longer true after adjusting for age and tissue thickness. Interestingly, differences in TBS were still highly significant in those under 60 yr of age even with adjustment for tissue thickness, but not in older subjects. There were 74 CAs and 56 AAs with vertebral fractures on vertebral fracture assessment (17% vs 14%, p = 0.30). In CA, the odds ratio (OR) for prevalent vertebral fracture per SD decrease in TBS was 2.33 (p < 0.001), whereas in AA, the OR was 1.43 (p = 0.02). In a multivariate logistic regression model that also included age, BMD T-score, and glucocorticoid use, the association between TBS and prevalent vertebral fractures was still highly significant in CAs (OR 1.54, p = 0.008) but not in AAs (OR 1.23, p = 0.21). Our results suggest that TBS may be less discriminatory in regard to fracture risk in AAs than in CAs and that TBS may need to be used differently in these 2 ethnic groups