Abhay Asthana

Mannosylated Chitosan Nanoparticles for Delivery of Antisense Oligonucleotides for Macrophage Targeting

The therapeutic potential of antisense oligonucleotides (ASODN) is primarily dependent upon its safe and efficient delivery to specific cells overcoming degradation and maximizing cellular uptake in vivo. The present study focuses on designing mannosylated low molecular weight (LMW) chitosan nanoconstructs for safe ODNs delivery by macrophage targeting. Mannose groups were coupled with LMW chitosan and characterized spectroscopically. Mannosylated chitosan ODN nanoparticles (MCHODN NPs) were formulated by self-assembled method using various N/P ratio (moles of amine groups of MCH to phosphate moieties of ODNs) and characterized for gel retardation assay, physicochemical characteristics, cytotoxicity and transfection efficiency, and antisense assay. Complete complexation of MCH/ODN was achieved at charge ratio of 1:1 and above. On increasing the N/P ratio of MCH/ODN, particle size of the NPs decreased whereas zeta potential (ZV) increased. MCHODN NPs displayed much higher transfection efficiency into Raw 264.7 cells (bears mannose receptors) than Hela cells and no significant toxicity was observed at all MCH concentrations. Antisense assay revealed that reduction in lipopolysaccharide (LPS) induced serum TNF-α is due to antisense activity of TJU-2755 ODN (sequence complementary to 3′-UTR of TNF-α). These results suggest that MCHODN NPs are acceptable choice to improve transfection efficiency in vitro and in vivo.

In Vitro and In Vivo Evaluation of Niosomal Formulation for Controlled Delivery of Clarithromycin

The present study was focused on formulating and evaluating clarithromycin (CLR) containing niosomal formulation for in vitro and in vivo pharmacokinetic behavior. Niosomal formulations (empty and drug loaded) were prepared by using different ratio of surfactant (various Span grades 20, 40, 60, and 80) and cholesterol by thin film hydration method and were evaluated for in vitro characteristics, stability studies, and in vivo study. Dicetyl phosphate (DCP) was added to the niosomal formulation. Various pharmacokinetic parameters were determined from plasma of male SD rats. Span 60 containing niosomal formulation NC2 (cholesterol to surfactant ratio 1 : 1) displayed highest entrapment efficiency with desired particle size of 4.67 μm. TEM analyses showed that niosomal formulation was spherical in shape. Niosomes containing Span 60 displayed higher percentage of drug release after 24 h as compared to other formulations. NC2 formulation was found to be stable at the end of the study on storage condition. Various pharmacokinetic parameters, namely, AUC, AUMC, and MRT of niosomal formulation, were found to be 1.5-fold, 4-fold, and 3-fold plain drug, respectively. The present study suggested that niosomal formulations provide sustained and prolonged delivery of drug with enhance bioavailability.

QbD-enabled systematic development of gastroretentive multiple-unit microballoons of itopride hydrochloride

Abstract The objectives of present studies were to develop the systematically optimized multiple-unit gastroretentive microballoons, i.e. hollow microspheres of itopride hydrochloride (ITH) employing quality by design (QbD)-based approach. Initially, the patient-centric QTPP and CQAs were earmarked, and preliminary studies were conducted to screen the suitable polymer, solvent, solvent ratio, pH and temperature conditions. Microspheres were prepared by non-aqueous solvent evaporation method employing Eudragit S-100. Risk assessment studies carried out by constructing Ishikawa cause-effect fish-bone diagram, and techniques like risk estimation matrix (REM) and failure mode effect analysis (FMEA) facilitated the selection of plausible factors affecting the drug product CQAs, i.e. percent yield, entrapment efficiency (EE) and percent buoyancy. A 33 Box–Behnken design (BBD) was employed for optimizing CMAs and CPPs selected during factor screening studies employing Taguchi design, i.e. drug–polymer ratio (X1), stirring temperature (X2) and stirring speed (X3). The hollow microspheres, as per BBD, were evaluated for EE, particle size and drug release characteristics. The optimum formulation was embarked upon using numerical desirability function yielding excellent floatation characteristics along with adequate drug release control. Drug-excipient compatibility studies employing FT-IR, DSC and powder XRD revealed absence of significant interaction among the formulation excipients. The SEM studies on the optimized formulation showed hollow and spherical nature of the prepared microspheres. In vivo X-ray imaging studies in rabbits confirmed the buoyant nature of the hollow microspheres for 8 h in the upper GI tract. In a nutshell, the current investigations report the successful development of gastroretentive floating microspheres for once-a-day administration of ITH.

Development and Evaluation of Nanoemulsifying Preconcentrate of Curcumin for Colon Delivery

The present study aimed to develop and optimize a nanoemulsifying preconcentrate formulation of curcumin with good emulsification ability and optimal globule size, for controlled targeting in colon. Content of formulation variables, namely, X 1 (Peceol), X 2 (Cremophor-EL), and X 3 (Transcutol HP), were optimized by Box-Behnken design of experiments for its impact on mean globule size (Y 1), emulsification time (Y 2), and time required for drug release (85%) in phosphate buffer (pH 7.2), t 85% (Y 3). Transmission electron micrographs confirmed that there is no coalescence among globules, with size range concordant with the globule size analysis by dynamic light scattering technique (100 nm). 3D plots indicated that concentration of formulation ingredients significantly influences the formulation properties (globule size, emulsification time, and drug release). In vitro release profile (in phosphate buffer; pH 7.2) represents the fact that more than 50% of the drug was released within initial 15 min whereas in vivo release showed limited systemic absorption (C max 200 ng/mL) of curcumin. Stability study ensures the protection of drug in alkaline media which may further confirm the localised delivery of drug to colonic region. Study demonstrated that the nanoemulsifying preconcentrate can be a promising system for the colon specific delivery of curcumin to treat local pathologies.

Development and Optimization of Polymeric Self-Emulsifying Nanocapsules for Localized Drug Delivery: Design of Experiment Approach

The purpose of the present study was to formulate polymeric self-emulsifying curcumin nanocapsules with high encapsulation efficiency, good emulsification ability, and optimal globule size for localized targeting in the colon. Formulations were prepared using modified quasiemulsion solvent diffusion method. Concentration of formulation variables, namely, X 1 (oil), X 2 (polymeric emulsifier), and X 3 (adsorbent), was optimized by design of experiments using Box-Behnken design, for its impact on mean globule size (Y 1) and encapsulation efficiency (Y 2) of the formulation. Polymeric nanocapsules with an average diameter of 100–180 nm and an encapsulation efficiency of 64.85 ± 0.12% were obtained. In vitro studies revealed that formulations released the drug after 5 h lag time corresponding to the time to reach the colonic region. Pronounced localized action was inferred from the plasma concentration profile (C max 200 ng/mL) that depicts limited systemic absorption. Roentgenography study confirms the localized presence of carrier (0–2 h in upper GIT; 2–4 h in small intestine; and 4–24 h in the lower intestine). Optimized formulation showed significantly higher cytotoxicity (IC50 value 20.32 μM) in HT 29 colonic cancer cell line. The present study demonstrates systematic development of polymeric self-emulsifying nanocapsule formulation of curcumin for localized targeting in colon.

Etodolac Containing Topical Niosomal Gel: Formulation Development and Evaluation

The present study aimed to investigate the delivery potential of Etodolac (ETD) containing topical niosomal gel. Niosomal formulations were prepared by thin film hydration method at various ratios of cholesterol and Span 60 and were evaluated with respect to particle size, shape, entrapment efficiency, and in vitro characteristics. Dicetyl phosphate (DCP) was also added in the niosomal formulation. Mean particle size of niosomal formulation was found to be in the range of 2 μm to 4 μm. Niosomal formulation N2 (1 : 1) ratio of cholesterol and surfactant displayed good entrapment efficiency (96.72%). TEM analyses showed that niosomal formulation was spherical in shape. Niosomal formulation (N2) displayed high percentage of drug release after 24 h (94.91) at (1 : 1) ratio of cholesterol : surfactant. Further selected niosomal formulation was used to formulate topical gel and was characterized with respect to its various parameters such as pH, viscosity, spreadability, ex vivo study, and in vivo potential permeation. Ex vivo study showed that niosomal gel possessed better skin permeation study than the plain topical gel. Further in vivo study revealed good inhibition of inflammation in case of topical niosomal gel than plain gel and niosomal formulation. The present study suggested that topical niosomal gel formulations provide sustained and prolonged delivery of drug.

Formulation and Characterization of Antimicrobial Herbal Mouthwash from Some Herbal Extracts for Treatment of Periodontal Diseases

Soussan Irani1, Alireza Monsef Esfahani2, Shahram Sabeti3 and Farahnaz Bidari Zerehpoush3 1Assistant Professor, Department of Oral Pathology, Dental Faculty, Hamadan University, Hamadan, Iran 2Professor, Department of Pathology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. 3Assistant Professor ,Pathology Department, Loghman Hospital, Shahid Beheshti University, Tehran, IranIntroduction: Camphorquinone (CQ) is popularly-used as photosensitizer in resin composites and dentin bonding agents (DBA). The purpose of this study is to investigate the influences of CQ on cytotoxicity to human dental pulp cells. Then, its effects on the expression of cell cycle and apoptosis related genes and proteins are evaluated. Besides, the relationship between ROS formation and its toxicity is also observed.Lingual thyroid (LT) is a developmental disorder due to the failure of the thyroid gland to migrate from its anlage, foramen caecum to its prelaryngeal site. Lingual position represents the most frequent ectopic location accounting up to 90% of ectopic cases. It is found at the junction of the anterior two thirds and the posterior third, between the epiglottis and the circumvallate papillae, often asymptomatic but growing may cause local symptoms as upper airway obstruction, disphagia and hemorrhage at any time from infancy to adulthood. Thyroid scintigraphy plays the most important role in diagnosing ectopic thyroid gland but neck ultrasound, neck CTscan, neck MRI contribute as well. Treatment of this anomaly includes exogenous Lthyroxine hormone administration, radioiodine ablation therapy and surgery.BACKGROUND Dental crowding is the one of the most frequently encountered problem for an orthodontist. The relationship between crowding and various skeletal, dental and soft tissue parameters is important to establish and consider during the overall orthodontic treatment planning. This study aimed to determine the correlation of maxillary and mandibular base lengths with dental arch crowding in different malocclusions and to evaluate the gender dimorphism for these variables. METHODS A sample of 120 subjects divided into three skeletal malocclusions was further subdivided based on amount of mandibular arch crowding. Maxillary and mandibular base lengths and dental arch crowding were measured on pre-treatment lateral cephalograms and initial casts using vernier calliper respectively. Inter-group comparisons were assessed by univariate analysis of variance. Correlation between base lengths and dental crowding was assessed by Pearsons correlation (p≤0.05). RESULTS Statistically significant differences were found for maxillary (p=0.008) and mandibular base lengths (p=0.000) between different skeletal malocclusions. Mandibular base length was significantly larger in males (p=0.000). Mandibular crowding was highest in class-II and lowest in class-I (p=0.01). A significant but weak negative correlation was found between dental crowding and maxillary (r=-0.28, p=0.02) and mandibular (r=-0.20, p=0.02) base lengths, significant but moderate positive correlation between maxillary and mandibular base lengths (r=0L566, -0.000) and between maxillary and mandibular crowding (r=-0.408, p-0.000). CONCLUSIONS Maxillary and mandibular base lengths are largest in skeletal class-II and class-III malocclusions respectively. Mandibular base length is larger in males as compared to females. An increase in amount of dental crowding is weakly associated with smaller skeletal base lengths.Background: The limitations and morbidity associated with autogenous bone grafting have driven the search for predictable bone substitutes and bioimplants. Stem cells offer an interesting tool for tissue engineering, thus the purpose of this study was to observe and compare the regenerative capacity of artificial alveolar bone defect after autogenous bone grafting versus seeding of Adipose TissueDerived Stem cells (ADSCs) either alone or in combination with demineralized bone matrix (DBM). Methodology: Standardized bilateral buccal dehiscence defects (4 × 3 × 3 mm) were surgically created in 24 healthy dogs and divided into 6 groups , Control group, Autogenous bone graft group, ADSCs group, ADSCs together with autogenous bone grafting, DBM group and finally ADSCs and DBM group. All animals were subjected to histological and histomorphometric analysis. Results: Histolgic and histomorphometric analysis within the same group revealed that the coronal mean values were higher in control, ADSCs with DBM and DBM groups and the apical values were higher in the three other groups. Conclusion: This study demonstrated that the adipose derived stem cells with DBM have potential as a suitable alternative to autogenous bone in the treatment of alveolar bone defect. 3rd FUE Dental Conference Cairo 2016, April Abstract.......................................................................................................................... iiiAlthough various treatment modalities are available, which aim at the correction of a Class III malocclusion during the growth period, these have proved unsuccessful in maintaining the results for a long time. Retention appliances are required to be worn until growth is complete. And relying on the patient to cooperate over long and extent treatment protocols is a potential problem in achieving successful,stable treatment results. Surgical intervention may be still needed in a few cases.