A clinical perspective of chitosan nanoparticles for infectious disease management.

Infectious diseases and their effective management are still a challenge in this modern era of medicine. Diseases, such as the SARS-CoV-2, Ebola virus, and Zika virus, still put human civilization at peril. Existing drug banks, which include antivirals, antibacterial, and small-molecule drugs, are the most advocated method for treatment, although effective but they still flounder in many instances. This calls for finding more effective alternatives for tackling the menace of infectious diseases. Nanoformulations are progressively being implemented for clinical translation and are being considered a new paradigm against infectious diseases. Natural polymers like chitosan are preferred to design nanoparticles owing to their biocompatibility, biodegradation, and long shelf-life. The chitosan nanoparticles (CNPs) being highly adaptive delivers contemporary prevention for infectious diseases. Currently, they are being used as antibacterial, drug, and vaccine delivery vehicles, and wound-dressing materials, for infectious disease treatment. Although the recruitment of CNPs in clinical trials associated with infectious diseases is minimal, this may increase shortly due to the sudden emergence of unknown pathogens like SARS-CoV-2, thus turning them into a panacea for the management of microorganisms. This review particularly focuses on the all-around application of CNPs along with their recent clinical applications in infectious disease management.

Mucoadhesive drug delivery systems: a promising noninvasive approach to bioavailability enhancement. Part II: formulation considerations.

INTRODUCTION: Mucoadhesive drug delivery systems (MDDS) are specifically designed to interact and bind to the mucosal layer of the epithelium for localized, prolonged, and/or targeted drug delivery. Over the past 4 decades, several dosage forms have been developed for localized as well as systemic drug delivery at different anatomical sites. AREAS COVERED: The objective of this review is to provide a detailed understanding of the different aspects of MDDS. Part II describes the origin and evolution of MDDS, followed by a discussion of the properties of mucoadhesive polymers. Finally, a synopsis of the different commercial aspects of MDDS, recent advances in the development of MDDS for biologics and COVID-19 as well as future perspectives are provided. EXPERT OPINION: A review of the past reports and recent advances reveal MDDS as highly versatile, biocompatible, and noninvasive drug delivery systems. The rise in the number of approved biologics, the introduction of newer highly efficient thiomers, as well as the recent advances in the field of nanotechnology have led to several excellent applications of MDDS, which are predicted to grow significantly in the future.

Possible Role of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Recovery of Post-COVID-19 Anosmia.

Purpose: Anosmia or hyposmia, with or without taste changes, are common symptoms that occur in SARS-CoV-2 infection and frequently persist as post-COVID-19 manifestations. This is the first trial to assess the potential value of using local ivermectin in the form of a mucoadhesive nanosuspension nasal spray to treat post-COVID-19 anosmia. Methods: It is a controlled, randomized trial. Participants were recruited from South Valley University Hospitals in Qena, Upper Egypt, from the ENT and Chest Diseases Departments and outpatient clinics. Patients with persistent post COVID-19 anosmia were randomly divided into two groups, the first group "ivermectin group" included 49 patients treated by ivermectin nanosuspension mucoadhesive nasal spray (two puffs per day). The second group included 47 patients "placebo group" who received saline nasal spray. Follow- up of anosmia [using Visual analogue scale (VAS)] in all patients for three months or appearance of any drug related side effects was done. Results: The mean duration of pre-treatment post COVID-19 anosmia was 19.5± 5.8 days in the ivermectin group and 19.1± 5.9 days in the placebo group,p˃0.05. Regarding the median duration of anosmia recovery, the ivermectin group recovered from post COVID-19 anosmia in 13 days compared to 50 days in the placebo group, p˂ 0.001. Following the first week of ivermectin nanosuspension mucoadhesive nasal spray therapy, the ivermectin group had a significantly higher percentage of anosmia recovery (59.2%) than the placebo group (27.7%), p˂ 0.01, with no significant differences in recovery rates between the two groups at 1, 2, and 3 months of follow up, p˃0.05. Conclusion: In the small number of patients treated, local Ivermectin exhibited no side effects. In persistent post-COVID-19 anosmia, it could be used for one week at the most as the treatment was extended to one, two and three months, with no difference in recovery compared to the placebo treatment. Trial Registration No: NCT04951362.

A Review on Xerostomia and Its Various Management Strategies: The Role of Advanced Polymeric Materials in the Treatment Approaches.

The medical term xerostomia refers to the subjective sensation of oral dryness. The etiology seems to be multifactorial with the most frequently reported causes being the use of xerostomic medications, neck and head radiation, and systematic diseases (such as Sjögren's syndrome). Xerostomia is associated with an increased incidence of dental caries, oral fungal infections, and difficulties in speaking and chewing/swallowing, which ultimately affect the oral health-related quality of life. The development of successful management schemes is regarded as a highly challenging project due to the complexity of saliva. This is why, in spite of the fact that there are therapeutic options aiming to improve salivary function, most management approaches are alleviation-oriented. In any case, polymers are an integral part of the various formulations used in every current treatment approach, especially in the saliva substitutes, due to their function as thickening and lubricating agents or, in the case of mucoadhesive polymers, their ability to prolong the treatment effect. In this context, the present review aims to scrutinize the literature and presents an overview of the role of various polymers (or copolymers) on either already commercially available formulations or novel drug delivery systems currently under research and development.

Advances in the Prophylaxis of Respiratory Infections by the Nasal and the Oromucosal Route: Relevance to the Fight with the SARS-CoV-2 Pandemic.

In this time of COVID-19 pandemic, the strategies for prevention of the infection are a primary concern. Looking more globally on the subject and acknowledging the high degree of misuse of protective face masks from the population, we focused this review on alternative pharmaceutical developments eligible for self-defense against respiratory infections. In particular, the attention herein is directed to the nasal and oromucosal formulations intended to boost the local immunity, neutralize or mechanically "trap" the pathogens at the site of entry (nose or mouth). The current work presents a critical review of the contemporary methods of immune- and chemoprophylaxis and their suitability and applicability in topical mucosal dosage forms for SARS-CoV-2 prophylaxis.

New Formulations Loading Caspofungin for Topical Therapy of Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) poses a significant problem worldwide affecting women from all strata of society. It is manifested as changes in vaginal discharge, irritation, itching and stinging sensation. Although most patients respond to topical treatment, there is still a need for increase the therapeutic arsenal due to resistances to anti-infective agents. The present study was designed to develop and characterize three hydrogels of chitosan (CTS), Poloxamer 407 (P407) and a combination of both containing 2% caspofungin (CSP) for the vaginal treatment of VVC. CTS was used by its mucoadhesive properties and P407 was used to exploit potential advantages related to increasing drug concentration in order to provide a local effect. The formulations were physically, mechanically and morphologically characterized. Drug release profile and ex vivo vaginal permeation studies were performed. Antifungal efficacy against different strains of Candida spp. was also evaluated. In addition, tolerance of formulations was studied by histological analysis. Results confirmed that CSP hydrogels could be proposed as promising candidates for the treatment of VVC.

Silymarin/curcumin loaded albumin nanoparticles coated by chitosan as muco-inhalable delivery system observing anti-inflammatory and anti COVID-19 characterizations in oleic acid triggered lung injury and in vitro COVID-19 experiment.

Respiratory infected by COVID-19 represents a major global health problem at moment even after recovery from virus corona. Since, the lung lesions for infected patients are still sufferings from acute respiratory distress syndrome including alveolar septal edema, pneumonia, hyperplasia, and hyaline membranes Therefore, there is an urgent need to identify additional candidates having ability to overcome inflammatory process and can enhance efficacy in the treatment of COVID-19. The polypenolic extracts were integrated into moeties of bovine serum albumin (BSA) and then were coated by chitosan as a mucoadhesion polymer. The results of interleukin-6, and c-reactive protein showed significant reduction in group treated by Encap. SIL + CUR (64 ± 0.8 Pg/µL & 6 ± 0.5 µg/µL) compared to group treated by Cham. + CUR (102 ± 0.8 Pg/µL & 7 ± 0.5 µg/µL) respectively and free capsules (with no any drug inside) (148 ± 0.6 Pg/µL & 10 ± 0.6 µg/µL) respectively. Histopathology profile was improved completely. Additionally, encapsulating silymarin showed anti-viral activity in vitro COVID-19 experiment. It can be summarized that muco-inhalable delivery system (MIDS) loaded by silymarin can be used to overcome inflammation induced by oleic acid and to overcome COVID-19.

Mucoadhesive silver nanoparticle-based local drug delivery system for peri-implantitis management in COVID-19 era. Part 1: antimicrobial and safety in-vitro analysis.

BACKGROUND: Pseudomonas aeruginosa, a major respiratory pathogen, has been isolated from peri-implant sites and is associated with dental implant failure. This in-vitro study (part 1) aimed to fabricate a novel mucoadhesive silver nanoparticle-based local drug delivery chip, evaluate its antimicrobial efficacy against P. aeruginosa, and its safety for the treatment of peri-implantitis. MATERIALS AND METHODS: Silver nanoparticles were synthesized and characterized using a transmission electron microscope (TEM). The local drug delivery chip was fabricated using gelatin, glycerol, silver nanoparticle solution (2.5 µg/ml, 5 µg/ml, 7.5 µg/ml, and 10 µg/ml), glutaraldehyde, and sodium alginate solution. These chips were evaluated for physical parameters, effect on viability of murine macrophage cell line J774A.1, and antimicrobial activity (using Kirby-Bauer disc diffusion method with 18 h incubation period) against P. aeruginosa ATCC 27853. RESULTS: Silver nanoparticle antimicrobial chip exhibited dimensions of 4 mm × 5 mm x 0.4 mm, 5.8 mg weight, pH 5-6, folding endurance 1.04, and one-year stability. P. aeruginosa was susceptible to ≥ 7.5 µg/ml concentration of silver nanoparticles (spherical shape with particle size ranging from 10 to 100 nm). Murine macrophage cells exhibited 93% viability after 24 h incubation with silver nanoparticle chips. CONCLUSION: The novel silver nanoparticle chip showed dimensional stability, minimal effect on murine macrophage cell viability, and significant antimicrobial activity against P. aeruginosa. With the further establishment of its effective dosage and safety, this chip could be used as an adjunct to mechanical debridement (as a non-aerosol generating procedure) in treating peri-implantitis, especially during the ongoing coronavirus disease 2019 (COVID-19) pandemic.

Intranasal vaccine: Factors to consider in research and development.

Most existing vaccines for human use are administered by needle-based injection. Administering vaccines needle-free intranasally has numerous advantages over by needle-based injection, but there are only a few intranasal vaccines that are currently approved for human use, and all of them are live attenuated influenza virus vaccines. Clearly, there are immunological as well as non-immunological challenges that prevent vaccine developers from choosing the intranasal route of administration. We reviewed current approved intranasal vaccines and pipelines and described the target of intranasal vaccines, i.e. nose and lymphoid tissues in the nasal cavity. We then analyzed factors unique to intranasal vaccines that need to be considered when researching and developing new intranasal vaccines. We concluded that while the choice of vaccine formulations, mucoadhesives, mucosal and epithelial permeation enhancers, and ligands that target M-cells are important, safe and effective intranasal mucosal vaccine adjuvants are needed to successfully develop an intranasal vaccine that is not based on live-attenuated viruses or bacteria. Moreover, more effective intranasal vaccine application devices that can efficiently target a vaccine to lymphoid tissues in the nasal cavity as well as preclinical animal models that can better predict intranasal vaccine performance in clinical trials are needed to increase the success rate of intranasal vaccines in clinical trials.

Inhalable nanocatchers for SARS-CoV-2 inhibition.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.