Current Pharmacologic Options and Emerging Therapeutic Approaches for the Management of Ulcerative Colitis: A Narrative Review.

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disorder (IBD) with periods of relapse and remission. Current advancements in clinical research have led to the development of more refined and effective medical therapy for UC. Summary of the Evidence: Traditional therapeutic agents such as 5-aminosalicylates (5-ASAs), sulfasalazine (SASP), corticosteroids, and immunomodulatory drugs have remained the gold standard for decades. However, their novel formulations and dosage regimens have changed their sequences in the medical management of UC. Several other novel drugs are in the final phases of clinical development or have recently received regulatory approval designed to target specific mechanisms involved in the inflammatory cascade for UC. Conclusions: This narrative review sought to provide a comprehensive knowledge of the potential benefits of standard and emerging therapies, including novel formulations, new chemical entities, and novel therapeutic approaches in managing UC. Keywords: Ulcerative colitis, 5- Aminosalicylic acid, sulfasalazine, corticosteroids, biologics, immunomodulators, novel formulations.

Comprehensive review of Hesperetin: Advancements in pharmacokinetics, pharmacological effects, and novel formulations.

Hesperetin is a flavonoid compound naturally occurring in the peel of Citrus fruits from the Rutaceae family. Previous studies have demonstrated that hesperetin exhibits various pharmacological effects, such as anti-inflammatory, anti-tumor, antioxidative, anti-aging, and neuroprotective properties. In recent years, with the increasing prevalence of diseases and the rising awareness of traditional Chinese medicine, hesperetin has garnered growing attention for its wide-ranging pharmacological effects. To substantiate its health benefits and elucidate potential mechanisms, knowledge of pharmacokinetics is crucial. However, the limited solubility of hesperetin restricts its bioavailability, thereby diminishing its efficacy as a beneficial health agent. To enhance the bioavailability of hesperetin, various novel formulations have been developed, including nanoparticles, liposomes, and cyclodextrin inclusion complexes. This article reviews recent advances in the pharmacokinetics of hesperetin and methods to improve its bioavailability, as well as its pharmacological effects and mechanisms, aiming to provide a theoretical basis for clinical applications.

Assessing the therapeutic and toxicological profile of novel GLP-1 receptor agonists for type 2 diabetes.

INTRODUCTION: GLP-1 receptor agonists provide multiple benefits for patients with type 2 diabetes. Nonetheless, there are also several significant adverse effects associated with these agents. A thorough understanding of both therapeutic and toxicological profiles of GLP-1 receptor agonists is crucial for appropriate utilization of this medication class. A literature search of PubMed and ClinicalTrials.gov was carried out to inform discussion on the topic. AREAS COVERED: This review article discusses the key advantages and disadvantages derived from the use of GLP-1 receptor agonists in the treatment of type 2 diabetes. Landmark trials which helped characterize the cardiovascular and renal benefits of GLP-1 receptor agonists are highlighted. We also discuss key studies still in progress and new formulations under investigation. EXPERT OPINION: GLP-1 receptor agonists provide glycemic and complication-risk reduction benefits for individuals with type 2 diabetes. Current data suggests there is a lot of potential for further applications, even outside of type 2 diabetes management. It would be of particular interest to see the range of benefits conferred from GLP-1 receptor agonists in individuals without type 2 diabetes. Broader application of these medications could be expected given the ongoing development of new oral formulations and combination agents.

Drug Delivery for Ocular Allergy: Current Formulation Design Strategies and Future Perspectives.

The incidences of ocular allergy have been growing with the increase in pollution. Because of challenges in new drug development, there have been efforts to maximize the efficacy of existing drugs through drug delivery approaches. The effectiveness of drugs in ophthalmic conditions is primarily determined by permeability across the barrier, corneal retention, and sustained release. Thus, there have been widespread efforts to optimize these parameters to enhance efficacy through novel formulations. This review aims to analyze the approaches to drug delivery systems to encourage further research to optimize effectiveness. With this objective, research on drug delivery aspects of anti-allergy therapeutics was included and analyzed based on formulation/drug delivery technique, Food and Drug Administration approval limits, residence time, compatibility, pre-clinical efficacy, and potential for translational application. Conventional eye drops have concerns such as poor residence time and ocular bioavailability. The novel formulations have the potential to improve residence and bioavailability. However, the use of preservatives and the lack of regulatory approval for polymers limit the translational application. The review may assist readers in identifying novel drug delivery strategies and their limitations for the development of effective ophthalmic formulations for the treatment of ocular allergy.

Enhanced Efficacy of Carvedilol by Utilization of Solid Dispersion and Other Novel Strategies: A Review.

Carvedilol is classified as a second class drug of Biopharmaceutical classification system (BCS), and it is an excellent beta blocker and vasodilating agent. It is used in a diverse range of disease states. Despite having tremendous advantages, the drug cannot be used effectively and productively due to aquaphobicity and poor bioavailability. To overcome this limitation, numerous novel approaches and tactics have been introduced over the past few years, such as Selfmicro emulsifying drug delivery systems (SMEDDS), nanoparticles, solid dispersions and liposomal drug delivery. The present review aims to accentuate the role of solid dispersion in improving the dissolution profile and aqua solubility of carvedilol and also to emphasize other novel formulations of carvedilol proposed to prevail the limitations of carvedilol. Solid dispersion and other novel approaches were found to play a significant role in overcoming the drawbacks of carvedilol, among which solid dispersion is the most feasible and effective approach being used worldwide. Reduced particle size, more wettability, and large surface area are obtained by the implementation of solid dispersion technique, hence improving carvedilol solubility and bioavailability.

Contemporary Aspects of Designing Marine Polysaccharide Microparticles as Drug Carriers for Biomedical Application.

The main goal of modern pharmaceutical technology is to create new drug formulations that are safer and more effective. These formulations should allow targeted drug delivery, improved drug stability and bioavailability, fewer side effects, and reduced drug toxicity. One successful approach for achieving these objectives is using polymer microcarriers for drug delivery. They are effective for treating various diseases through different administration routes. When creating pharmaceutical systems, choosing the right drug carrier is crucial. Biomaterials have become increasingly popular over the past few decades due to their lack of toxicity, renewable sources, and affordability. Marine polysaccharides, in particular, have been widely used as substitutes for synthetic polymers in drug carrier applications. Their inherent properties, such as biodegradability and biocompatibility, make marine polysaccharide-based microcarriers a prospective platform for developing drug delivery systems. This review paper explores the principles of microparticle design using marine polysaccharides as drug carriers. By reviewing the current literature, the paper highlights the challenges of formulating polymer microparticles, and proposes various technological solutions. It also outlines future perspectives for developing marine polysaccharides as drug microcarriers.

Natamycin Ocular Delivery: Challenges and Advancements in Ocular Therapeutics.

Fungal keratitis, an ocular fungal infection, is one of the leading causes of monocular blindness. Natamycin has long been considered the mainstay drug used for treating fungal keratitis and is the only US Food and Drug Administration (USFDA)-approved drug, commercially available as a topical 5% w/v suspension. Furthermore, ocular fungal infection treatment takes a few weeks to months to recover, and the available marketed antifungal suspensions are associated with poor residence time, limited bioavailability (< 5%) and high dosing frequency as well as minor irritation and discomfort. Despite these challenges, natamycin is still the preferred drug choice for treating fungal keratitis, as it has fewer side effects and less ocular toxicity and is more effective against Fusarium species than other antifungal agents. Several novel therapeutic approaches for the topical delivery of natamycin have been reported to overcome the challenges posed by the conventional dosage forms and to improve ocular bioavailability for the efficient management of fungal keratitis. Current progress in the delivery systems uses approaches aimed at improving the corneal residence time, bioavailability and antifungal potency, thereby reducing the dose and dosing frequency of natamycin. In this review, we discuss the various strategies explored to overcome the challenges present in ocular drug delivery of natamycin and improve its bioavailability for ocular therapeutics.

Zeolites as Ingredients of Medicinal Products.

Development of new medicinal products for particular therapeutic treatment or for better manipulations with better quality and less side effects are possible as a result of advanced inorganic and organic materials application, among which zeolites, due to their properties and versatility, have been gaining attention. This paper is an overview of the development in the use of zeolite materials and their composites and modifications as medicinal products for several purposes such as active agents, carriers, for topical treatments, oral formulations, anticancer, the composition of theragnostic systems, vaccines, parenteral dosage forms, tissue engineering, etc. The objective of this review is to explore the main properties of zeolites and associate them with their drug interaction, mainly addressing the advances and studies related to the use of zeolites for different types of treatments due to their zeolite characteristics such as molecule storage capacity, physical and chemical stability, cation exchange capacity, and possibility of functionalization. The use of computational tools to predict the drug-zeolite interaction is also explored. As conclusion was possible to realize the possibilities and versatility of zeolite applications as being able to act in several aspects of medicinal products.

Formulation Strategies for Enhancing Pharmaceutical and Nutraceutical Potential of Sesamol: A Natural Phenolic Bioactive.

Natural plants and their products continue to be the major source of phytoconstituents in food and therapeutics. Scientific studies have evidenced the benefits of sesame oil and its bioactives in various health conditions. Various bioactives present in it include sesamin, sasamolin, sesaminol, and sesamol; among these, sesamol represents a major constituent. This bioactive is responsible for preventing various diseases including cancer, hepatic disorders, cardiac ailments, and neurological diseases. In the last decade, the application of sesamol in the management of various disorders has attracted the increasing interest of the research community. Owing to its prominent pharmacological activities, such as antioxidant, antiinflammatory, antineoplastic, and antimicrobial, sesamol has been explored for the above-mentioned disorders. However, despite the above-mentioned therapeutic potential, its clinical utility is mainly hindered owing to low solubility, stability, bioavailability, and rapid clearance issues. In this regard, numerous strategies have been explored to surpass these restrictions with the formulation of novel carrier platforms. This review aims to describe the various reports and summarize the different pharmacological activities of sesamol. Furthermore, one part of this review is devoted to formulating strategies to improve sesamol's challenges. To resolve the issues such as the stability, low bioavailability, and high systemic clearance of sesamol, novel carrier systems have been developed to open a new avenue to utilize this bioactive as an efficient first-line treatment for various diseases.

Analysis of drug factors in 5-aminolevulinic acid photodynamic therapy for oral potentially malignant disorder.

OBJECTIVES: This study aimed to analyze the influence of drug factors on the efficacy of 5-aminolevulinic acid (ALA) photodynamic therapy for oral potentially malignant disorder to improve clinical efficacy and promote clinical rational drug use. METHODS: Literature on the treatment of oral potentially malignant disorder by using ALA photodynamic therapy was collected and analyzed from PubMed, ISI Web of Knowledge database, CNKI, VIP, and Wanfang database. RESULTS: A total of 690 cases were collected, with an average complete response rate of 65.94%. The groups treated with 16.8% methyl aminolevulinate cream, local topical, once a week, and pre-activation time of 2-4 hours were better than the other subgroups, with average complete response rates of 100%, 66.91%, 78.28%, and 77.54%, respectively. CONCLUSIONS: Drug factors have direct influence on the curative effect. The development of novel oral ALA formulations from the perspective of drug improvement is an important strategy to improve efficacy.

Current Innovations in the Development of Functional Gummy Candies.

Nowadays, consumers are aware of the necessity of following a healthy diet and there is demand for natural and nutritious food products, especially for children. Consequently, new trends in the food industry are focused on the development of foods with low levels of sucrose and artificial additives (e.g., flavors and colorants), as well as high antioxidant, protein, and fiber content. On the other hand, some consumers demand vegan, halal, and kosher-certified food products. In this regard, conventional confectionary products such as gummy candies (GCs) are increasingly losing their popularity. Therefore, the development of plant-based and functional GCs has gained the attention of researchers and manufacturers. This review highlights recent innovations in the development of GCs with alternative gelling agents and sweeteners, natural flavors and colorants, and the incorporation of medicines, fiber, protein and antioxidants into GCs. Additionally, it summarizes their effects on the techno-functional, sensory, and nutritional properties of GCs.

Pharmacological Effects and Clinical Prospects of Cepharanthine.

Cepharanthine is an active ingredient separated and extracted from Stephania cepharantha Hayata, a Menispermaceae plant. As a bisbenzylisoquinoline alkaloid, cepharanthine has various pharmacological properties, including antioxidant, anti-inflammatory, immunomodulatory, antitumoral, and antiviral effects. Following the emergence of coronavirus disease 2019 (COVID-19), cepharanthine has been found to have excellent anti-COVID-19 activity. In this review, the important physicochemical properties and pharmacological effects of cepharanthine, particularly the antiviral effect, are systematically described. Additionally, the molecular mechanisms and novel dosage formulations for the efficient, safe, and convenient delivery of cepharanthine are summarized.

Formulation considerations for improving intranasal delivery of CNS acting therapeutics.

One of the principal impediments for the treatment of neurological conditions is the lack of ability of most of the medicinal agents to evade the blood-brain barrier. Among all the novel approaches to bypass the blood-brain barrier, nose to brain transport is the most patient compliant, non-invasive and effective approach. It directly transports drugs to the CNS via the trigeminal and olfactory nerves present in the nasal cavity. This review article focuses on anatomy and physiology of nasal cavity, potential of intranasal drug delivery, mechanisms of drug transport to brain, its advantages and limitations, novel intranasal formulations, marketed products, factors affecting nose to brain transport, formulation consideration of intranasal products and the future perspectives of CNS targeting via intranasal drug administration.

Novel and emerging treatment options for acne vulgaris

The principal actors in acne are the sebaceous gland, keratinocytes of the follicle and skin microbiome/innate immunity. Current acne treatments are frequently accompanied by side effects or may cause antibacterial resistance. New formulations and emerging treatments with novel mechanisms of action and improved formulations have recently been made available or are currently under development. This review provides an update on the most recent advances in topical or systemic acne therapy related to recent data on the pathophysiology of acne. A review of the most recent literature about new and emerging acne treatments since 2016 listed in the PubMed and Clinicaltrials.gov database was performed by a group of dermatologists interested in acne (GEA). Several novel treatments have been made available or are currently under development, including Clascosterone, Trifarotene and Sarecy-cline, as well as more effective and better tolerated formulations of existing compounds, such as Minocycline, Tretinoin, Tazarotene and Lidose-isotretinoin, and emerging acne therapies (including hyaluronic acid, cannabidiol, modulators of the skin microbiota, insulin-like growth factor, vaccines, bacteriophages, probiotics and antimicrobial peptides), targeting the sebaceous gland and its activity, inflammation or keratinocytes of the follicle and skin microbiome including Cutibacterium acnes. Recently, in addition to other fixed combinations, a fixed combination of adapalene and benzoyl peroxide that targets acne scars has been made available for the first time. The newly available products and other potentially emerging treatment options will increase the armamentarium of acne therapies and potentially reduce its prevalence worldwide.

Novel Hydrogels for Topical Applications: An Updated Comprehensive Review Based on Source.

Active pharmaceutical ingredients (API) or drugs are normally not delivered as pure chemical substances (for the prevention or the treatment of any diseases). APIs are still generally administered in prepared formulations, also known as dosage forms. Topical administration is widely used to deliver therapeutic agents locally because it is convenient and cost-effective. Since earlier civilizations, several types of topical semi-solid dosage forms have been commonly used in healthcare society to treat various skin diseases. A topical drug delivery system is designed primarily to treat local diseases by applying therapeutic agents to surface level parts of the body such as the skin, eyes, nose, and vaginal cavity. Nowadays, novel semi-solids can be used safely in pediatrics, geriatrics, and pregnant women without the possibility of causing any allergy reactions. The novel hydrogels are being used in a wide range of applications. At first, numerous hydrogel research studies were carried out by simply adding various APIs in pure form or dissolved in various solvents to the prepared hydrogel base. However, numerous research articles on novel hydrogels have been published in the last five to ten years. It is expected that novel hydrogels will be capable of controlling the APIs release pattern. Novel hydrogels are made up of novel formulations such as nanoparticles, nanoemulsions, microemulsions, liposomes, self-nano emulsifying drug delivery systems, cubosomes, and so on. This review focus on some novel formulations incorporated in the hydrogel prepared with natural and synthetic polymers.

An Insight into the Dermatological Applications of Neem: A Review on Traditional and Modern Aspect.

BACKGROUND: Dermatological disorders are cutaneous infirmities which are frequently occurring and increasing at an alarming rate. These range from mild itching/redness (dermatitis) to fatal skin cancers and has posed a major health concern. Azadirachta indica A. Juss (commonly known as neem), a member of Meliaceae family, is an Indian medicinal plant which has been known for its health promoting effects since ancient times. OBJECTIVE: The review highlights the traditional practices, pharmacological aspects, and formulatory approach of neem for the treatment of dermatological disorders. Further, recent patents and novel delivery systems (developed and in pipeline) improving skin delivery and therapeutic profile of neem are discussed. RESULTS: Neem is a traditional medicinal plant that has been employed for the prevention and treatment of numerous ailments covering systemic and topical disorders. Scientific studies have validated the traditional claims of neem and attributed these health benefits to the presence of more than 300 structurally diverse and complex compounds. It possesses anti-inflammatory, antibacterial, analgesic, antiviral, antifungal, immunomodulatory and antioxidant activities which substantiate its use as skin therapy. Various novel formulations and associated patents that improved the permeability of neem based products across skin could be found in literature. CONCLUSION: Critical appraisal of available literature revealed that neem possesses anti-microbial, anti-inflammatory, antioxidant and antiseptic properties. Thus it has the potential to be developed as a single effective therapy for the management of multimodal skin disorders. Further, pharmaceutical tailoring of neem by implication of novel carriers could enhance its penetrability across skin.

Small Airways, Big Problem: Extrafine beclomethasone/formoterol in asthma and chronic obstructive pulmonary disease.

Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases characterized by an inflammatory process that extends from the central to peripheral airways. Conventional pressurized metered-dose inhalers and most dry-powder inhalers emit drug particles too large to target the small airways effectively. Advancements in drug formulation have given rise to a new generation of inhalers that can generate aerosols with extrafine drug particles that leads to more effective aerosol penetration into the lung periphery. An extrafine formulation of inhaled beclomethasone/formoterol (BDP-FF) with enhanced lung deposition is now available. This document reviews the various real-world and controlled studies that have evaluated the efficacy of extrafine BDP-FF in asthma and COPD.

Emerging Nanomedicines for the Treatment of Atopic Dermatitis.

Globally, the prevalence of Atopic dermatitis (AD) is significantly increasing and affecting around 20% of population including children. Complex interactions amongst abnormality in epidermal barrier function, environment, infectious agents and immunological defects are considered as key factors in the pathogenesis of AD. Although the role of oxidative stress has been studied in some skin diseases, investigation of the same in AD is intermittent. Calcineurin inhibitors and/or topical corticosteroids are currently available; however, it causes atrophy of the skin, burning sensation, and systemic side effects which leads to poor patient compliance. These limitations provoke the strong need to develop an innovative approach in managing AD. Nanomaterials for effective drug delivery to skin conditions such as AD have attracted a lot of attention owing to its ability to encapsulate, protect, and release the cargo at the diseased skin site. However, there are lots of unmet challenges especially in terms of development of non-toxic formulations and clinical translation of established nanomedicines in the form of accessible products. Numerous formulations have emerged as carrier for poorly soluble and permeable drugs, viz., lipidic, polymeric, metal, silica, liposomes, hydrocarbon gels and this field is evolving. This review is intended to provide an insight incidences associated with pathophysiology of AD and challenges with existing treatments of AD. Focus is kept on reviewing current development and emerging nanomedicines for effective treatment of AD. The review also inculcates merits of several nanomedicines in overcoming challenges of existing products and its future implications.

Novel formulation development from Ophiocordyceps sinensis (Berk.) for management of high-altitude maladies.

Ophiocordyceps sinensis (Berk.) is a fungus closely related to medicinal mushroom, which belongs to the family Ophiocordycipitaceae. It is a well-known and rich herbal source of bioactive active constituents. The medicinal mushroom has garnered worldwide attention owing to its multifarious bioactivities. This mushroom grows on the larva of ghost moths (Hepialidae) and produces fruiting bodies, which serve as a vital natural source of medicine and supplementary diets. On account of the diverse pharmacological and bioactive constituents present in O. sinensis, it has been established as a potential antioxidant, anticancer, antibacterial, anti-proliferative, anti-inflammatory agent that has been successfully used for treating several health issues, including hypoxia-related problems encountered by mountaineers, pilgrims, tourists and soldiers occurring at high-altitude regions such as acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), high-altitude cerebral edema (HACE), frostbite, chilblains, hypothermia, etc. The most important pharmacologically active compounds present in the O. sinensis include nucleobases and its derivatives (adenosine, cordycepin, 3-deoxyadenosine, AMP, GMP, UMP, guanosine, uridine), polysaccharides (mannose, glucose, galactose, rhamnose, arabinose, xylose, galactose), proteins, peptides and steroids. This article focuses on the various research endeavors undertaken to scientifically establish the medicinal properties of O. sinensis, highlighting the various principally active compounds, their pharmacological action, drug designing and development and future perspective for various health benefits.

Recent Advances in the Novel Formulation of Docosahexaenoic Acid for Effective Delivery, Associated Challenges and Its Clinical Importance.

Docosahexaenoic Acid (DHA) is an essential polyunsaturated omega-3 fatty acid, and a fundamental structural component of the phospholipid membranes, especially of neural and retinal cells. DHA is found to be critical for the normal development and functioning of neurons and synaptogenesis in the brain, and is required during pre- and post-natal stages of life. DHA has also been observed to exhibit neuroprotective, cardioprotective, and anti-inflammatory properties. However, geographical dietary variations and poor economic conditions lead to insufficient DHA levels resulting in various health deficits like improper brain development, cognitive disorders, and other clinical complications. Thus, to prevent its deficiency-induced derangements, several authorities recommend DHA as a supplement during pregnancy, infancy, and throughout adulthood. In past decades, the soft gelatin capsule was only feasible resolute of DHA, but due to their limitations and invention of new technologies; it led to the development of new dosage forms with improved physicochemical characteristics of DHA. This article will discuss in detail about the role of DHA in brain development, microalgae oil as an emerging source of DHA, clinical- and pharmacological-activities of DHA, issues related to DHA oil, current formulation of DHA along with their application, limitations, and strategies used for improvement and future prospectives.