Sporadic regional re-emergent cholera: a 19th century problem in the 21st century.

Cholera, caused by Vibrio cholerae, is a severe diarrheal disease that necessitates prompt diagnosis and effective treatment. This review comprehensively examines various diagnostic methods, from traditional microscopy and culture to advanced nucleic acid testing like polymerase spiral reaction and rapid diagnostic tests, highlighting their advantages and limitations. Additionally, we explore evolving treatment strategies, with a focus on the challenges posed by antibiotic resistance due to the activation of the SOS response pathway in V. cholerae. We discuss promising alternative treatments, including low-pressure plasma sterilization, bacteriophages, and selenium nanoparticles. The paper emphasizes the importance of multidisciplinary approaches combining novel diagnostics and treatments in managing and preventing cholera, a persistent global health challenge. The current re-emergent 7th pandemic of cholera commenced in 1961 and shows no signs of abeyance. This is probably due to the changing genetic profile of V. cholerae concerning bacterial pathogenic toxins. Given this factor, we argue that the disease is effectively re-emergent, particularly in Eastern Mediterranean countries such as Lebanon, Syria, etc. This review considers the history of the current pandemic, the genetics of the causal agent, and current treatment regimes. In conclusion, cholera remains a significant global health challenge that requires prompt diagnosis and effective treatment. Understanding the history, genetics, and current treatments is crucial in effectively addressing this persistent and re-emergent disease.

Dual stimuli-responsive polymeric nanoparticles combining soluplus and chitosan for enhanced breast cancer targeting.

A dual stimuli-responsive nanocarrier was developed from smart biocompatible chitosan and soluplus graft copolymers. The copolymerization was investigated by differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA), and Fourier transform infrared (FTIR). The optimized chitosan-soluplus nanoparticles (CS-SP NPs) were further used for the encapsulation of a poorly water-soluble anticancer drug. Tamoxifen citrate (TC) was used as the model drug and it was loaded in CS-SP NPs. TC CS-SP NPs were characterized in terms of particle size, zeta potential, polydispersity, morphology, encapsulation efficiency, and physical stability. The nanoparticles showed homogenous spherical features with a size around 94 nm, a slightly positive zeta potential, and an encapsulation efficiency around 96.66%. Dynamic light scattering (DLS), in vitro drug release, and cytotoxicity confirmed that the created nano-system is smart and exhibits pH and temperature-responsive behavior. In vitro cellular uptake was evaluated by flow cytometry and confocal microscopy. The nanoparticles revealed a triggered increase in size upon reaching the lower critical solution temperature of SP, with 70% of drug release at acidic pH and 40 °C within the first hour and a 3.5-fold increase in cytotoxicity against MCF7 cells incubated at 40 °C. The cellular uptake study manifested that the prepared nanoparticles succeeded in delivering drug molecules to MCF7 and MDA-MB-231 cells. In summary, the distinctive characteristics provided by these novel CS-SP NPs result in a promising nano-platform for effective drug delivery in cancer treatment.

From cell factories to patients: Stability challenges in biopharmaceuticals manufacturing and administration with mitigation strategies.

Active ingredients of biopharmaceuticals consist of a wide array of biomolecular structures, including those of enzymes, monoclonal antibodies, nucleic acids, and recombinant proteins. Recently, these molecules have dominated the pharmaceutical industry owing to their safety and efficacy. However, their manufacturing is hindered by high cost, inadequate batch-to-batch equivalence, inherent instability, and other quality issues. This article is an up-to-date review of the challenges encountered during different stages of biopharmaceutical production and mitigation of problems arising during their development, formulation, manufacturing, and administration. It is a broad overview discussion of stability issues encountered during product life cycle i.e., upstream processing (aggregation, solubility, host cell proteins, color change), downstream bioprocessing (aggregation, fragmentation), formulation, manufacturing, and delivery to patients.

Deep Eutectic Liquids as a Topical Vehicle for Tadalafil: Characterisation and Potential Wound Healing and Antimicrobial Activity.

Deep eutectic solvents (DESs) and ionic liquids (ILs) offer novel opportunities for several pharmaceutical applications. Their tunable properties offer control over their design and applications. Choline chloride (CC)-based DESs (referred to as Type III eutectics) offer superior advantages for various pharmaceutical and therapeutic applications. Here, CC-based DESs of tadalafil (TDF), a selective phosphodiesterase type 5 (PDE-5) enzyme inhibitor, were designed for implementation in wound healing. The adopted approach provides formulations for the topical application of TDF, hence avoiding systemic exposure. To this end, the DESs were chosen based on their suitability for topical application. Then, DES formulations of TDF were prepared, yielding a tremendous increase in the equilibrium solubility of TDF. Lidocaine (LDC) was included in the formulation with TDF to provide a local anaesthetic effect, forming F01. The addition of propylene glycol (PG) to the formulation was attempted to reduce the viscosity, forming F02. The formulations were fully characterised using NMR, FTIR and DCS techniques. According to the obtained characterisation results, the drugs were soluble in the DES with no detectable degradation. Our results demonstrated the utility of F01 in wound healing in vivo using cut wound and burn wound models. Significant retraction of the cut wound area was observed within three weeks of the application of F01 when compared with DES. Furthermore, the utilisation of F01 resulted in less scarring of the burn wounds than any other group including the positive control, thus rendering it a candidate formula for burn dressing formulations. We demonstrated that the slower healing process associated with F01 resulted in less scarring potential. Lastly, the antimicrobial activity of the DES formulations was demonstrated against a panel of fungi and bacterial strains, thus providing a unique wound healing process via simultaneous prevention of wound infection. In conclusion, this work presents the design and application of a topical vehicle for TDF with novel biomedical applications.

Advances in buccal and oral delivery of insulin.

Diabetes mellitus is a metabolic endocrine disease characterized by chronic hyperglycemia with disturbances in metabolic processes, such as those related to carbohydrates, fat, and protein. There are two main types of this disease: type 1 diabetes (T1D) and type 2 diabetes (T2D). Insulin therapy is pivotal to the management of diabetes. Over the last two decades, many routes of administration, including nasal, pulmonary, rectal, transdermal, buccal, and ocular, have been investigated. Nevertheless, subcutaneous parenteral administration is still the most common route for insulin therapy. To overcome poor bioavailability and the barriers to oral insulin absorption, novel approaches in the field of oral drug delivery and administration have been brought about by the coalescence of different branches of nanoscience and nanotechnology, such as nanomedicine, nano-biochemistry, and nano-pharmacy. Novel drug delivery systems, including nanoparticles, nano-platforms, and nanocarriers, have been suggested. The objective of this review is to provide an update on the various promising approaches that have been explored and evaluated for the safe and efficient oral and buccal administration of insulin.

Evaluation of a novel water-soluble decanoic acid formulation as a fruit sanitizer.

Fruits irrigated with contaminated water can transmit various pathogens. High sugar content in fruits such as black cherry (BC) fruit encourages microbial proliferation. A novel water-soluble decanoic acid (WSDA) was evaluated as a fruit sanitizer and compared with other traditional fruit sanitizers such as ethanol, bleach, or dishwasher surfactants. WSDA sanitizer killed yeasts, molds and bacteria including E. coli microbes effectively as other sanitizers with (4 log cycle reduction) of microbial load. Furthermore, the bacterial sanitization mechanism i.e. bactericidal or bacteriostatic was evaluated for alcohol, bleaching and WASDA solutions. E. coli was selected as the model pathogen used for such comparison. Results indicated that the mechanism of action for the three sanitizer solutions against E. coli was bactericidal. The problem with most used fruit sanitizers is their negative influence on fruit quality in terms of physical, mechanical and taste properties. In addition, some led to toxicological and ecological concerns. Thus, studies were conducted to explore the changes in the exocarp cell structure of BC fruit upon exposure to WSDA and other sanitizers using microscopic investigation. WSDA could have a very mild or gentle effect on the BC fruit cells compared to other sanitizers. Alcohol, bleaching and dishwasher surfactant changed the cellular structures and the intercellular spaces. Sanitizers may also affect fruit swelling. WSDA showed an increase in percent weight gain but it was significantly (p < 0.05) much lower than dishwasher surfactant and bleaching solution. BC Fruit flesh firmness and hardness were investigated upon exposure to different sanitizer solutions. BC fruit treated with WSDA showed the highest firmness values. Some liquid sanitizers could affect fruit quality in terms of fruit taste. Sensory evaluation in terms of the sanitizer's smell, texture and hedonic of BC fruit after soaking in different sanitizers was carried out. All sensory parameters of BC fruit soaked with WSDA were similar with insignificant differences (p > 0.05) compared to BC fruit soaked in tap water. However, the sensory parameters were significantly different (p < 0.05) when compared with alcohol, bleach and dishwasher surfactant. This ensures that WSDA was superior to other evaluated sanitizers in terms of physical, mechanical and fruit quality.

Stabilization of insulin using low molecular weight chitosan carbonate nanocarrier.

The current study aims to design a nanoparticulate system that could encapsulate insulin and improve its stability. Nanoparticles were formulated by ionic cross-linking of chitosan (CS) with carbonate divalent anions. The interaction between the two moieties was evidenced by AFM, FTIR and surface tension measurements. CS carbonate nanoparticles were prepared with different mole fractions. The mole fraction of carbonate that produced the smallest size nanoparticles and highest zeta potential (40 nm and +39 mV, respectively) was determined. Circular dichroism (CD) studies revealed that insulin conformation was not affected by CS at 20 °C. However, the studies at elevated temperatures demonstrated that CS had a role in insulin stabilization. Fluorescence spectroscopy indicated the interaction between insulin and CS carbonate. The findings from this investigation showed the potential use of CS carbonate as an insulin stabilizer and at the same time as an insulin nanocarrier system.

Chitosan-biotin topical film: preparation and evaluation of burn wound healing activity.

A new composite film from chitosan (CS) and biotin (BIO) was developed to enhance burn wound healing. The film was prepared by electrostatic interaction between CS and BIO. Four different ratios of CS to BIO v/v (4:1, 3:2, 2:3, and 1:4) were prepared. The films were comprehensively characterized using FTIR, DSC, and AFM. The in-vitro release studies showed that the most promising formula with the highest release behavior was CS to BIO 1: 4. The ex vivo adhesion times were reported as 0.50 ± 0.30 min for CS film compared to 6.2 ± 0.30, 8.4 ± 0.40, 11.2 ± 0.50, and 13.83 ± 1.04 min for CS to BIO films v/v (1:4, 2:3, 3:2 and 4:1), respectively. Most importantly, the skin healing activities of CS/BIO film in the excision wound model in mice and skin burn model in rats showed faster rates of healing compared to CS and placebo. Furthermore, skin stretching and burn wound contraction behavior treated with CS/BIO were higher than that of CS treated skin. In conclusion, the results obtained revealed that CS/BIO films possessed superior burn wound healing activity compared to CS.

A review of the antiviral activity of Chitosan, including patented applications and its potential use against COVID-19.

Chitosan is an abundant organic polysaccharide, which can be relatively easily obtained by chemical modification of animal or fungal source materials. Chitosan and its derivatives have been shown to exhibit direct antiviral activity, to be useful vaccine adjuvants and to have potential anti-SARS-CoV-2 activity. This thorough and timely review looks at the recent history of investigations into the role of chitosan and its derivatives as an antiviral agent and proposes a future application in the treatment of endemic SARS-CoV-2.

Chitosan/lecithin liposomal nanovesicles as an oral insulin delivery system.

In the present work, insulin-chitosan polyelectrolyte complexes associated to lecithin liposomes were investigated as a new carrier for oral delivery of insulin. The preparation was characterized in terms of particle size, zeta potential and encapsulation efficiency. Surface tension measurements revealed that insulin-chitosan polyelectrolyte complexes have some degree of hydrophobicity and should be added to lecithin liposomal dispersion and not the vice versa to prevent their adsorption on the surface. Stability of insulin was enhanced when it was associated to liposomes. Significant reduction of blood glucose levels was noticed after oral administration of liposomal preparation to streptozotocin diabetic rats compared to control. The hypoglycemic activity was more prolonged compared to subcutaneously administered insulin.

Development of insulin loaded mesoporous silica injectable particles layered by chitosan as a controlled release delivery system.

The present work investigated the possibility of using mesoporous silica nanoparticles coated with low molecular weight chitosan as an injectable controlled release carrier of insulin. Insulin was totally encapsulated in particles. Surface tension measurements indicated that insulin was absorbed into mesoporous silica pores and interacted with chitosan. The stability of the encapsulated insulin was confirmed by different analytical methods such as RP-HPLC, FTIR and CD. Furthermore, the thermal stability using DSC was in the favor of the encapsulated insulin compared to free insulin. In vivo results indicated that insulin release was prolonged after loading into mesoporous silica nanoparticles. Such particles could be a potential carrier to control the release of insulin.