Chitosan and chito-oligosaccharide: a versatile biopolymer with endless grafting possibilities for multifarious applications.

Chito-oligosaccharides (COS), derived from chitosan (CH), are attracting increasing attention as drug delivery carriers due to their biocompatibility, biodegradability, and mucoadhesive properties. Grafting, the process of chemically modifying CH/COS by adding side chains, has been used to improve their drug delivery performance by enhancing their stability, targeted delivery, and controlled release. In this review, we aim to provide an in-depth study on the recent advances in the grafting of CH/COS for multifarious applications. Moreover, the various strategies and techniques used for grafting, including chemical modification, enzymatic modification, and physical modification, are elaborated. The properties of grafted CH/COS, such as stability, solubility, and biocompatibility, were reported. Additionally, the review detailed the various applications of grafted CH/COS in drug delivery, including the delivery of small drug molecule, proteins, and RNA interference therapeutics. Furthermore, the effectiveness of grafted CH/COS in improving the pharmacokinetics and pharmacodynamics of drugs was included. Finally, the challenges and limitations associated with the use of grafted CH/COS for drug delivery and outline directions for future research are addressed. The insights provided in this review will be valuable for researchers and drug development professionals interested in the application of grafted CH/COS for multifarious applications.

Diagnostic accuracy and management concordance of otorhinolaryngological diseases through telehealth or remote visits: A systematic review & meta-analysis.

INTRODUCTION: COVID-19 has led to delays in providing healthcare in both emergency and non-emergency settings, especially in surgical subspecialties which rely heavily on referrals and in-person visits. Without an established telehealth infrastructure, many otorhinolaryngological departments experienced decreases in consultations. Telemedicine has attempted to bridge the gap between pre- and post-pandemic periods by creating a safe avenue of communication between otorhinolaryngologists and patients. This review hopes to address the accuracy of telemedicine in patient diagnosis and management. METHODS: Searches were conducted since study conception until June 30, 2022, on multiple databases including PubMed, SCOPUS, and CINAHL for this systematic review and meta-analysis. Diagnostic accuracy, management accuracy, kappa, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were meta-analyzed by comparing virtual visits to in-person visits (gold standard). RESULTS: Nineteen studies were included in this review. A total of 1518 patients were included across all studies. When comparing virtual visits against in-person visits, accurate diagnosis was made in 86.2% [82.1,89.9, I2 = 73.5%, P < 0.0001] of patients and management accuracy was 91.5% [86.1,95.7, I2 = 81.8%, P < 0.0001] when treating patients. Kappa value determining interrater reliability was 0.8 [0.7,0.9, I2 = 81.8%, P < 0.0001]. CONCLUSION: Our data suggest that diagnostic and management concordance is above 80% when comparing diagnosis and management strategies in patients who underwent both telehealth and in-person visits with an otorhinolaryngologist. In uncomplicated patients, telehealth might be a reliable source for diagnosis and management however, in-person consultation is likely still required for pathologies in which physical exam, imaging or procedural elements represent a vital component of the work-up.

Disease-Modifying Antirheumatic Drugs in the Treatment of Autoimmune Inner Ear Disease: A Systematic Review and Meta-Analysis of Auditory and Vestibular Outcomes.

OBJECTIVE: To answer the following question: In patients with primary autoimmune inner ear disease (AIED), (population) what impact do disease-modifying antirheumatic agents (DMARDs) (intervention) when compared with no treatment or corticosteroids (comparison) have on auditory and vestibular outcomes (outcome)? STUDY DESIGN: Systematic review and meta-analysis. DATA SOURCES: According to PRISMA guidelines, PubMed, Scopus, CINAHL, and Cochrane Library databases were searched from inception to March 10, 2022. STUDY SELECTION: Studies of patients receiving DMARDs for the treatment of AIED were selected for review. Case reports, phase I/II trials, studies of patients with secondary AIED, and studies of AIED patients receiving solely corticosteroids were excluded. DATA EXTRACTION: Primary outcomes were pure-tone audiometry and speech discrimination scores at baseline and after DMARD treatment. Secondary outcomes were rates of subjective audiovestibular complaints and rates of adverse reactions. No objective vestibular outcomes underwent meta-analysis. DATA SYNTHESIS: Mean differences were calculated using RevMan 5.4. Heterogeneity was assessed with the Q test and I2 statistic. Pooled prevalence rates of audiovestibular symptoms were expressed as a percentage with 95% confidence intervals. RESULTS: Ten studies with a total of 187 patients were included. Treatments included methotrexate, etanercept, azathioprine, anakinra, cyclophosphamide, rituximab, and infliximab. Mean treatment duration was 10.8 ± 22.2 months and mean follow-up was 13.7 ± 8.1 months. The pure-tone audiometry and speech discrimination scores mean differences between baseline and post-DMARD were -2.1 [-4.1, -0.1] dB and 13.9 [8.5, 19.4] %, respectively. Seven studies reported 38 adverse events, four of which were classified as serious. CONCLUSION: DMARDs showed statistically significant improvement in auditory outcomes, as well as subjective symptoms, with relatively low rates of adverse events. They warrant further exploration to better compare with corticosteroids.

Pharmacokinetics and in vivo distribution of optimized PLGA nanoparticles for pulmonary delivery of levofloxacin.

OBJECTIVES: The aim of this study was to develop and optimize levofloxacin loaded PLGA nanoparticles (LN) for pulmonary delivery employing screening and experimental design and evaluate their in-vitro and in-vivo performance. The objective was to achieve Mass Median Aerodynamic Diameter (MMAD) of LN of less than 5µm, sustain the drug release up to 120 h and a higher AUC/MIC at the site of action. METHODS: LN were prepared by modified emulsion solvent evaporation technique employing high speed homogenization, probe sonication and subsequent lyophilization. KEY FINDINGS: The Pareto chart from Placket Burman screening design revealed that homogenization speed and amount of PLGA were found to be significant (P < 0.05). Further analysis by 3 full-factorial design revealed that F-ratio was found to be far greater than the theoretical value (P < 0.05) for each regression model. CONCLUSION: The optimized formulation with desirability value 0.9612 showed mean particle size of 146 nm, MMAD of 4.40 µm and sustained the drug release up to 120 h in simulated lung fluid. Augmentation in Cmax (1.71-fold), AUC 0-∞ (5.46-fold), Mean Residence Time (6.64-fold) and AUC/MIC (6.21-fold) of LN through pulmonary route was found to significantly higher (P < 0.05) than levofloxacin (p. o.).

A rodent cage change insomnia model disrupts memory consolidation.

Insomnia involves disruption of sleep initiation, maintenance and/or overall quality, and may interfere with cognition. Here, we evaluated memory impairment produced by rodent mild (acute) insomnia models. Insomnia models consisted of either single or repeated exposure to cages previously occupied (dirtied) by an unfamiliar rat for 5-7 days. Rats were trained in the Morris water maze to remember the platform location (acquisition), and were then exposed to: (a) 6 hr of undisturbed baseline; (b) dirty cage change-induced insomnia (animal placed into a cage dirtied by another rat for 6 hr); or (c) double-dirty cage change-induced insomnia (animal placed into a cage dirtied by another rat for 3 hr, and then another dirty cage 3 hr later). The animal's memory for the platform location was then evaluated in a probe trial. Double-dirty cage change-induced insomnia significantly disrupted sleep, although the effects of dirty cage change-induced insomnia were overall not significant. In the fourth hour of double-dirty cage change-induced insomnia (following the second cage change), sleep episode number and duration alterations indicated sleep fragmentation. Furthermore, power spectral analysis revealed diminished wake and, to a lesser extent, rapid eye movement theta power (indicated by trend difference) in the last 3 hr of exposure. Significant deficits were noted for measures of water maze performance following double-dirty cage change-induced insomnia, indicating impaired memory. In summary, one variant of the rodent insomnia model, double-dirty cage change-induced insomnia, disrupted sleep and attenuated memory consolidation, indicating this paradigm may be useful to evaluate the effects of hypnotics on memory consolidation.

Self-nanoemulsifying drug delivery system of glimepiride: design, development, and optimization.

The objective of the present investigation was to develop and characterize the self-nanoemulsifying drug delivery system (SNEDDS) of glimepiride, a poorly soluble drug. Solubility of glimepiride in various vehicles was determined, and ternary phase diagrams were constructed using a suitable oil, surfactant, and cosurfactant system to find out the efficient self-emulsification system. A three factor, three level Box-Behnken statistical design was employed to explore the main and interaction effect of independent variables, namely X1 (amount of Capmul MCM), X2 (amount of Acrysol K 140), and X3 (amount of Transcutol P). Percent transmittance value (Y1), droplet diameter (Y2), and percent drug released at 5 min (Y3) were the dependent variables. Formulation optimization was carried out to optimize the droplet diameter and percent drug dissolved at 5 min. The batch prepared according to the optimized formulation showed a close agreement between observed and predicted values. Box-Behnken statistical design allowed us to understand the effect of formulation variables on the rapid dissolution of drug from SNEDDS and to optimize the formulation to obtain a rapid drug dissolution at 5 min. LAY ABSTRACT: A self-nanoemulsifying drug delivery system of glimepiride has been design, developed, and optimized. A three factor, three level Box-Behnken statistical design was employed to explore the main and interaction effect of independent variables, namely X1 (amount of Capmul MCM), X2 (amount of Acrysol K 140), and X3 (amount of Transcutol P). Percent transmittance value (Y1), droplet diameter (Y2), and percent drug released at 5 min (Y3) were the dependent variables. The Capmul MCM-Akcrysol K 140-Transcutol system was found to be the suitable ternary system that was able to release almost 80% of drug within the first 5 min. The improved dissolution of glimepiride might improve patient compliance.

Improvement of dissolution properties of lamotrigine by inclusion complexation and solid dispersion technique.

The aim of the present work was to improve the dissolution characteristics of the poorly water soluble antiepileptic drug lamotrigine (LMN) by inclusion complexation using hydroxy propyl beta-cyclodextrin (HP beta-CD) by co-evaporation technique and by, solid dispersion, prepared by the melt method using poloxamer 407 (L 127). Phase solubility studies showed AL type curves with both the carriers. Dissolution of LMN was significantly improved (p < 0.05) by inclusion complexation and solid dispersion preparation. Results of solid state characterization performed by Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimetry and Powder X-ray Diffractrometry techniques revealed a decrease in the crystallinity of LMN that might be accounting for improvement in the dissolution properties as seen from dissolution studies.