Formulation, Characterization and In Vitro Evaluation of Mesalamine and Bifidobacterium bifidum Loaded Hydrogel Beads in Capsule System for Colon Targeted Delivery.

Mesalamine is a first-line drug for the treatment of inflammatory bowel diseases. However, its premature release associated with marketed formulations leads to adverse effects like gastric trouble, vomiting, and diarrhoea. To minimize these side effects, colon-targeted drug delivery is essential. Besides conventional pharmacotherapy, bifidogenic probiotics with anti-inflammatory activity has been reported to elicit a significant impact on the remission of ulcerative colitis. Bifidogenic probiotics being acid-labile necessitate developing a gastro-resistant formulation for enhancing the delivery of viable cells to the colon. The present study was aimed at developing a fixed-dose unit dosage form of mucoadhesive hydrogel beads loaded with mesalamine and Bifidobacterium bifidum further encapsulated in Eudragit® capsules for the targeted drug delivery at colonic pH. The hydrogel beads were prepared by ionotropic gelation, with the effect of single and dual-crosslinking approaches on various formulation characteristics studied. Standard size 00 Eudragit® gastro-resistant capsules were prepared and the dried beads were filled inside the capsule shells. The formulation was then evaluated for various parameters, including physicochemical characterization, in vitro biocompatibility and anti-inflammatory activity. No interaction was observed between the drug and the polymers, as confirmed through FTIR, XRD, and DSC analysis. The mean particle size of the beads was ~ 457-485 µm. The optimized formulation showed a drug entrapment efficiency of 95.4 ± 2.58%. The Eudragit® capsule shells disintegrated in approximately 13 min at pH 7.4. The mucoadhesive hydrogel beads sustained the drug release above 18 h, with 50% of the drug released by the end of 12 h. The optimized formulation demonstrated significant (p < 0.05) gastro-resistance, biocompatibility, sustained drug release, cell viability, and anti-inflammatory activity.

Effect of Root Canal Taper on the Ability of Endodontically Treated Teeth using the TruNatomy and Protaper Next File Systems to Resist Fracture.

Objectives: This research was done to evaluate how the root canal taper affects the Endodontically Treated Teeth (ETT) prepared with the TruNatomy and Protaper Next file systems in terms of fracture resistance. Materials and Method: Forty recently extracted mandibular premolar teeth were used in this research, which was classified into four groups at random. Groups 1a and 1b used TruNatomy 4% and 6%, respectively, while groups 2a and 2b used the Protaper Next 4% and 6% file systems, respectively. The root canals were cleaned, shaped, and sealed using cold lateral compaction. The root canals were then fixed in standardized autopolymerizing acrylic resin blocks and tested for vertical root fracture using a universal testing machine. Newtons were used to measure the forces needed to cause fractures. Data were statistically analyzed. Results: In comparison with other groups, group 1a (TruNatomy 4%) displayed greater fracture resistance (423.322.43 Newtons), and group 2b (Protaper Next 6%) displayed the least fracture resistance (264.512.76 Newtons). Conclusion: Protaper Next file system had lower fracture resistance than TruNatomy file system. With the use of greater taper instruments, a notable decrease in the fracture resistance of ETT was observed.

Assessment of the Apical Transportation and Quantity of Root Canal Dentin Removed Using Different New Rotary File Systems: An Original Study.

Introduction: The rotary systems have found a common application in the clinical practice for the endodontic therapies. Hence, we compared three recent endodontic systems for the comparison of the dentine removal and the apical transportation particularly in the curved canals. Methods: Oneshape, Pro Taper Next, and Edgefile X3 were the three systems that were compared. Thirty maxillary mesio buccal canals of the human permanent teeth were compared due to its curved nature. The volume of dentin removed and apical transportation (mm) were measured using micro-computed tomographic imaging (mm). Both the coronal section and the entire canal length had their dentin removed in accordance with measurements. Total dentine removed, coronal dentine removed, and the canal transportations were compared for the three rotary file systems. The values were compared with appropriate statistical tests for evaluating the significance. Results: There was no statistically significant difference between the three file systems for the dentin removed. The mean canal transportation was 0.33 ± 0.12, 0.21 ± 0.25, and 0.23 ± 0.21 mm, respectively, for Oneshape, Pro Taper Next, and Typhoon CM. In terms of statistics, there were no appreciable variations among the three rotary tools for apical transfer. Conclusions: The three rotary systems were comparable for the apical transportation and the dentine removal. Despite variations in the magnitude of apical enlargements, none of the instrumentation methods detected apical transportation.

Cellulosic Nanowhiskers: Preparation and Drug Delivery Application.

Nanomaterials have applications in almost every field and among them, green nanomaterials have various biological applications. Green nanomaterials are specifically useful for drug and DNA delivery applications. Considering that cellulose is the most abundant and easily available biomolecule, it has been used for preparing greener cellulose nanomaterials. Cellulosic nanowhiskers are a cost-effective and green alternative to chemical non-viral gene delivery systems. Cellulose nanowhiskers are commonly extracted from plant sources, and they are generally prepared by sulfuric and hydrochloric acid hydrolysis of plant cellulose. In this review, the topic of cellulose nanowhiskers as green biocompatible materials for gene and drug delivery is discussed with several practical examples.

Assessment of Effect of Fixed Orthodontic Treatment on Gingival Health: An Observational Study.

BACKGROUND: Prime components of fixed orthodontic treatments decrease the self-cleansing ability of the tongue and the cheeks leading to an increase in production of bacterial plaque. Hence, the present study was undertaken for assessing the effect of fixed orthodontic treatment on gingival health. MATERIALS AND METHODS: A total of 120 patients who were scheduled orthodontic treatment were enrolled. Complete data records of all the patients were recorded. Intra- and extraoral radiographs were obtained and photographic records were noted in separate pro forma. Complete intraoral examination of all the patients was carried out for recording visible plaque, any inflammation (visible clinically), and gingival recession. Based on the assessment of gingival texture and capillary transparency, analysis of gingival biotype was done. Follow-up records were assessed. RESULTS: The mean visible plaque value before treatment and after treatment was found to be 3.11 and 5.81, respectively. The mean visible inflammation value before treatment and after treatment was found to be 2.89 and 15.43, respectively. The mean gingival recession score value before treatment and after treatment was found to be 0.19 and 0.383, respectively. A significant increase in the visible plaque value, visible inflammation value, and gingival recession score was observed posttreatment. While comparing the gingival biotype, it was seen that in both the maxillary and mandibular arches, there was an increase in the thick gingival biotype while there was a decrease in thin maxillary biotype. CONCLUSION: There is a significant increase in plaque accumulation, inflammation, and gingival recession following fixed orthodontic treatment. Hence, during the course of orthodontic treatment, regular oral prophylaxis should be done.

Complex composite odontoma associated with impacted tooth: A case report.

Odontomas are the most common type of odontogenic tumors and are generally asymptomatic. This paper describes the case of a complex composite odontoma in a patient who had an asymptomatic swelling in the maxillary molar region, along with the impacted third molar. In this case, surgical excision of the lesion was performed, and the impacted third molar was intentionally left in situ so that it could erupt to the level of occlusion.

Ofloxacin loaded gellan/PVA nanofibers - Synthesis, characterization and evaluation of their gastroretentive/mucoadhesive drug delivery potential.

The purpose of this investigation is to formulate a gastroretentive sustained drug release system for ofloxacin to improve its retention time, pharmacological activity, bioavailability and therapeutic efficacy in the stomach. Ofloxacin loaded gellan/poly vinyl alcohol (PVA) nanofibers were fabricated using a simple and versatile electrospinning technique. The fabricated nanofibers were evaluated for percent drug encapsulation efficiency and in vitro drug release in simulated gastric medium (pH1.2). The in vitro release profile and kinetic studies for drug indicated the sustained release of ofloxacin from the nanofibers through Fickian diffusion kinetics. The antimicrobial activity of the ofloxacin loaded nanofibers was assessed in comparison to the pure ofloxacin by means of minimal inhibitory concentrations (MIC) against microbial strains of Enterococcus faecalis, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The optimized ofloxacin loaded gellan/PVA nanofibers displayed biphasic drug release profile with considerable mucoadhesion and gastric retention in the rat's gastric mucosal membrane. Data obtained, suggested that the developed gastroretentive drug delivery can potentially enhance the pharmacological activity of ofloxacin and can also serve as a viable alternative for improving drug bioavailability via oral route.

PEGylation of a proprotein convertase peptide inhibitor for vaginal route of drug delivery: in vitro bioactivity, stability and in vivo pharmacokinetics.

Uterine proprotein convertase (PC) 6 is critical for embryo implantation in mice and women. It is also one of the PC family members that play a vital role in HIV infectivity. We hypothesized that inhibiting PC6 in the female reproductive tract (vagina, cervix and uterus), may protect women from both pregnancy and HIV infection. One key requirement to prove this concept in an animal model is a vaginally deliverable PC6 inhibitor. Nona-D-arginine (Poly R) is a potent peptide PC inhibitor and is able to inhibit HIV in cell culture. We modified Poly R by PEGylation with different strategies and determined their biochemical properties in vitro and in vivo. PEGylation at the C-terminus, regardless of the PEG size (30 kDa or 1239 Da) did not compromise the inhibitory potency of Poly R. In contrast, PEGylation at both termini (1239 Da) dramatically reduced its inhibitory activity. Poly R and C-PEGylated Poly Rs also showed equal potency in inhibiting a PC6-dependent cellular process critical for embryo implantation. Poly R and the equipotent C-PEGylated Poly Rs were further tested for their serum stability in vitro and pharmacokinetics in vivo following vaginal administration in mice. All Poly Rs were equally stable in mouse serum in vitro for 24h; C-PEGylated Poly Rs showed enhanced vaginal absorption and penetration across the vaginal mucosa/epithelium. This is the first report that C-terminal PEGylation significantly enhances the therapeutic properties of Poly R for vaginal drug delivery. Our findings also provide important insights into future design of Poly R derivatives.

Inhibition of proprotein convertase 5/6 activity: potential for nonhormonal women-centered contraception.

BACKGROUND: Proprotein convertase 5/6 (PC6) is critical for endometrial epithelial receptivity and stromal cell decidualization for embryo implantation in women. We hypothesized that inhibiting PC6 could block implantation for contraception. The aim of this study was to prove this concept using human cell models and rabbits. STUDY DESIGN: A potential PC6 inhibitor, C1239-PEG-Poly R, was biochemically confirmed to be a potent PC6 inhibitor. The potential contraceptive action of the inhibitor was then tested in decidualization of primary human endometrial stromal cells in a human trophoblast spheroid attachment model and in vivo in rabbits. RESULTS: The PC6 inhibitor C1239-PEG-Poly R inhibited in a dose-dependent manner both decidualization and spheroid attachment. Vaginal delivery of 200 µL of the inhibitor at a final concentration of 5 mM to rabbits over a 3-day period starting 6 days after mating resulted in a 60% decrease in implantation and, hence, pregnancy. CONCLUSIONS: This study presents proof of concept that PC6 inhibition has the potential to block embryo implantation, providing nonhormonal contraception for women.