Determination of 3-acetyl-11-keto-ß-boswellic acid in analytical and biological samples using streamlined and robust RP-HPLC method.

AKBA (3-acetyl-11-keto-ß-boswellic acid) is a phytoconstituent derived from Boswellia serrata extract and utilized in the management of rheumatoid arthritis. Drug delivery approaches showed interest in delivering AKBA with advanced nanotechnology. There is a need for a simple, sensitive, and robust HPLC method that can determine AKBA in complex nanoformulation and in vitro and ex vivo samples. In the proposed work, the RP-HPLC method was developed using a mobile phase comprising a mixture of acetonitrile : milli Q (90 : 10) at detection λmax 250 nm. The method exhibited a linearity of 250 to 20 000 ng mL-1 with a high correlation coefficient of 1. The limit of detection and limit of quantification for the analytes were found to be 41.32 ng mL-1 and 125.21 ng mL-1, respectively. In the accuracy study, the % recovery of AKBA was found to be 98% to 102%, and the precision study showed less than 2% relative standard deviation. The developed method was found to be robust under chromatographic conditions with changes in pH and mobile phase mixture ratio. The method was also explored for forced degradation study, and the results showed the successful separation of degradation products from the AKBA. Further, the RP-HPLC method was applied for the quantification of AKBA in topical nanoformulations and different matrices, such as skin matrices and adhesive tapes. The method was able to measure entrapment efficiency (93.13 ± 1.94%), drug loading (25.83 ± 0.54%), drug assay in a gel matrix (96.99 ± 3.89%), drug amount in stratum corneum (7.90 ± 0.62 µg cm-2), and drug amount in viable skin layers (33.94 ± 0.21 µg cm-2) with high-speed reproducibility. The developed method can be utilized for the routine analysis of AKBA in conventional and complex formulations in academia and industry.

Bridging the gap in rheumatoid arthritis treatment with hyaluronic acid-based drug delivery approaches.

Rheumatoid Arthritis (RA) is a chronic, inflammatory, auto-immune disease that is majorly associated with the degradation of the synovial linings of the joints. It is a progressive disease that reduces the life span in affected individuals. Nanoparticles involving hyaluronic acid (HA) have gained the limelight for designing target-specific and more effective drug delivery options for RA. HA is found abundantly in the synovial fluid and acts as a natural ligand for the CD44 receptors. The targeted delivery approach using CD44 as the target can help in minimizing off-target drug distribution. These HA-based surface-decorated nanocarriers, hydrogels, and MNs are cutting-edge strategies that promise tailored delivery, fewer side effects, and more patient adherence to address the common issues associated with RA therapy. Considering the above facts, this review attempts to discuss the role of HA in making more effective formulations for therapeutic delivery in treating RA. Additionally, it provides a comprehensive overview of the potential advancements, mainly in treating RA by HA-based topical, transdermal, and parenteral drug delivery systems, with relevant case studies. The existing difficulties and potential paths for future research on HA-based non-conventional formulations for the management of RA are also discussed.

Exploring polysaccharide-based bio-adhesive topical film as a potential platform for wound dressing application: A review.

Wound dressings act as a physical barrier between the wound site and the external environment, preventing additional harm; choosing suitable wound dressings is essential for the healing process. Polysaccharide biopolymers have demonstrated encouraging findings and therapeutic prospects in recent decades about wound therapy. Additionally, polysaccharides have bioactive qualities like anti-inflammatory, antibacterial, and antioxidant capabilities that can help the process of healing. Due to their excellent tissue adhesion, swelling, water absorption, bactericidal, and immune-regulating properties, polysaccharide-based bio-adhesive films have recently been investigated as intriguing alternatives in wound management. These films also mimic the structure of the skin and stimulate the regeneration of the skin. This review presented several design standards and functions of suitable bio-adhesive films for the healing of wounds. Additionally, the most recent developments in the use of bio-adhesive films as wound dressings based on polysaccharides, including hyaluronic acid, chondroitin sulfate, dextran, alginate, chitosan, cellulose, konjac glucomannan, gellan gum, xanthan gum, pectin, guar gum, heparin, arabinogalactans, carrageen, and tragacanth gum, are thoroughly discussed. Lastly, to create a road map for the function of polysaccharide-based bio-adhesive films in advanced wound care, their clinical performances and future challenges in making bio-adhesive films by three-dimensional bioprinting are summarized.

Exploring the potential of polysaccharide-based hybrid hydrogel systems for their biomedical and therapeutic applications: A review.

Hydrogels are a versatile category of biomaterials that have been widely applied in the fields of biomedicine for the last several decades. The three-dimensional polymeric crosslinked hydrophilic structures of the hydrogel can proficiently hold drugs, nanoparticles, and cells, making them a potential delivery system. However, disadvantages like low mechanical strength, poor biocompatibility, and unusual in-vivo biodegradation are associated with conventional hydrogels. To overcome these hurdles, hybrid hydrogels are designed using two or more structurally different polymeric units. Polysaccharides, characterized by their innate biocompatibility, biodegradability, and abundance, establish an ideal foundation for the development of these hybrid hydrogels. This review aims to discuss the studies that have utilized naturally occurring polysaccharides to prepare hybrid systems, which were aimed for various biomedical applications such as tissue engineering, bone and cartilage regeneration, wound healing, skin cancer treatment, antimicrobial therapy, osteoarthritis treatment, and drug delivery. Furthermore, this review extensively examines the properties of the employed polysaccharides within hydrogel matrices, emphasizing the advantageous characteristics that make them a preferred choice. Furthermore, the challenges associated with the commercial implementation of these systems are explored alongside an assessment of the current patent landscape.

Evolving Trends in Nanofibers for Topical Delivery of Therapeutics in Skin Disorders.

Nanotechnology has yielded nanostructure-based drug delivery approaches, among which nanofibers have been explored and researched for the potential topical delivery of therapeutics. Nanofibers are filaments or thread-like structures in the nanometer size range that are fabricated using various polymers, such as natural or synthetic polymers or their combination. The size or diameter of the nanofibers depends upon the polymers, the techniques of preparation, and the design specification. The four major processing techniques, phase separation, self-assembly, template synthesis, and electrospinning, are most commonly used for the fabrication of nanofibers. Nanofibers have a unique structure that needs a multimethod approach to study their morphology and characterization parameters. They are gaining attention as drug delivery carriers, and the substantially vast surface area of the skin makes it a potentially promising strategy for topical drug products for various skin disorders such as psoriasis, skin cancers, skin wounds, bacterial and fungal infections, etc. However, the large-scale production of nanofibers with desired properties remains challenging, as the widely used electrospinning processes have certain limitations, such as poor yield, use of high voltage, and difficulty in achieving in situ nanofiber deposition on various substrates. This review highlights the insights into fabrication strategies, applications, recent clinical trials, and patents of nanofibers for different skin disorders in detail. Additionally, it discusses case studies of its effective utilization in the treatment of various skin disorders for a better understanding for readers.

Enhanced skin drug delivery using dissolving microneedles: a potential approach for the management of skin disorders.

INTRODUCTION: For decades, finding effective long-term or disease-modifying treatments for skin disorders has been a major focus of scientists. The conventional drug delivery systems showed poor efficacy with high doses and are associated with side effects, which lead to challenges in adherence to therapy. Therefore, to overcome the limitations of conventional drug delivery systems, drug delivery research has focused on topical, transdermal, and intradermal drug delivery systems. Among all, the dissolving microneedles have gained attention with a new range of advantages of drug delivery in skin disorders such as breaching skin barriers with minimal discomfort and its simplicity of application to the skin, which allows patients to administer it themselves. AREAS COVERED: This review highlighted the insights into dissolving microneedles for different skin disorders in detail. Additionally, it also provides evidence for its effective utilization in the treatment of various skin disorders. The clinical trial status and patents for dissolving microneedles for the management of skin disorders are also covered. EXPERT OPINION: The current review on dissolving microneedles for skin drug delivery is accentuating the breakthroughs achieved so far in the management of skin disorders. The output of the discussed case studies anticipated that dissolving microneedles can be a novel drug delivery strategy for the long-term treatment of skin disorders.

Exploring the Mechanical Perspective of a New Anti-Tumor Agent: Melatonin.

Melatonin is a serotonin-derived pineal gland hormone with many biological functions like regulating the sleep-wake cycle, circadian rhythm, menstrual cycle, aging, immunity, and antioxidants. Melatonin synthesis and release are more pronounced during the night, whereas exposure to light decreases it. Evidence is mounting in favor of the therapeutic effects of melatonin in cancer prevention, treatment and delayed onset in various cancer subtypes. Melatonin exerts its anticancer effect through modification of its receptors such as melatonin 1 (MT1), melatonin 2 (MT2), and inhibition of cancer cell proliferation, epigenetic alterations (DNA methylation/demethylation, histone acetylation/deacetylation), metastasis, angiogenesis, altered cellular energetics, and immune evasion. Melatonin performs a significant function in immune modulation and enhances innate and cellular immunity. In addition, melatonin has a remarkable impact on epigenetic modulation of gene expression and alters the transcription of genes. As an adjuvant to cancer therapies, it acts by decreasing the side effects and boosting the therapeutic effects of chemotherapy. Since current treatments produce drug-induced unwanted toxicities and side effects, they require alternate therapies. A recent review article attempts to summarize the mechanistic perspective of melatonin in different cancer subtypes like skin cancer, breast cancer, hepatic cancer, renal cell cancer, non-small cell lung cancer (NSCLC), colon oral, neck, and head cancer. The various studies described in this review will give a firm basis for the future evolution of anticancer drugs.

Surface Modification of Lipid-Based Nanocarriers: A Potential Approach to Enhance Targeted Drug Delivery.

Nanocarriers have the utmost significance for advancements in drug delivery and nanomedicine technology. They are classified as polymer-based nanocarriers, lipid-based nanocarriers, viral nanoparticles, or inorganic nanoparticles, depending on their constituent parts. Lipid-based nanocarrier systems have gained tremendous attention over the years because of their noteworthy properties like high drug-loading capacity, lower toxicity, better bioavailability and biocompatibility, stability in the gastrointestinal tract, controlled release, simpler scale-up, and validation process. Nanocarriers still have some disadvantages like poor drug penetration, limited drug encapsulation, and poor targeting. These disadvantages can be overcome by their surface modification. Surface-modified nanocarriers result in controlled release, enhanced penetration efficiency, and targeted medication delivery. In this review, the authors summarize the numerous lipid-based nanocarriers and their functionalization through various surface modifiers such as polymers, ligands, surfactants, and fatty acids. Recent examples of newly developing surface-modified lipid-based nanocarrier systems from the available literature, along with their applications, have been compiled in this work.

Insight on updates in polysaccharides for ocular drug delivery.

Ocular drug delivery is a significantly challenging task due to the presence of various anatomical and physiological barriers in the eye. Naturally available polysaccharides, when used as drug vehicles provide increased retention time, bioavailability, and penetration due to their unique mucoadhesive and charge-possessing nature. This review discusses the polysaccharide-based drug delivery system for the eye. Polysaccharides like alginic acid, cellulose derivatives, chitosan, pectin, xanthan gum, gellan gum, and hyaluronic acid are reviewed in this report. Additionally, emphasis is given to some of the recently investigated polymers such as sugarcane bagasse cellulose, a polysaccharide extracted from the seeds of Manilkara zapota, and Tremella fuciformis polysaccharide as drug vehicles for effective ocular drug delivery. This review also provides insight on clinical status and FDA-approved polysaccharides for ophthalmic delivery of therapeutics.

Microneedles-based drug delivery strategies: A breakthrough approach for the management of pain.

Pain is a personalized event or body alarm system that can limit a patient's activities and lead to negative repercussions. The commercially available conventional treatment strategies like oral, parenteral, and topical drug delivery systems for pain management are associated with side effects and poor patient compliance. The transdermal route is eminent for its painless distribution. Among transdermal drug delivery system, microneedles (MNs) are gaining attention for their application with delivery at the deeper dermal layer because it bypasses the major barrier of the skin, easily accesses the skin dermal microcirculation, prevents damage to dermal blood vessels, and can be simply inserted into the skin without utilizing any additional applicator devices. Hence, considered a promising drug delivery strategy with high patient compliance. This review highlights the recent advancements of MNs in pain management. The present work mainly emphasizes all the case studies reported from the past 10 years that utilize MNs containing therapeutics in the treatment of chronic pain-associated diseases like rheumatoid arthritis, neuropathic pain, osteoarthritis, psoriatic arthritis, and atopic dermatitis. These studies have proven the efficacious application of MNs in the management of chronic pain and inflammation. The review also covered the clinical trials, patents, and future goals of pain management by using MNs.

Polysaccharide-based nanofibers for pharmaceutical and biomedical applications: A review.

Nanofibers are fibrous nanocarriers that can be synthesized from natural polymers, synthetic polymers, semiconducting materials, composite materials, and carbon-based materials. Recently, natural polysaccharides-based nanofibers are gaining attention in the field of pharmaceuticals and biomedical as these are biocompatible, biodegradable, non-toxic, and economic. Nanofibers can deliver a significant amount of drug to the targeted site and provide effective interaction of therapeutic agent at the site of action due to a larger surface area. Other important advantages of nanofibers are low density, high porosity, small pore size, high mechanical strength, and low cost. In this review, natural polysaccharides such as alginate, pullulan, hyaluronic acid, dextran, cellulose, chondroitin sulfate, chitosan, xanthan gum, and gellan gum are discussed for their characteristics, pharmaceutical utility, and biomedical applications. The authors have given particular emphasis to the several fabrication processes that utilize these polysaccharides to form nanofibers, and their recent updates in pharmaceutical applications such as drug delivery, tissue engineering, skin disorders, wound-healing dressings, cancer therapy, bioactive molecules delivery, anti-infectives, and solubility enhancement. Despite these many advantages, nanofibers have been explored less for their scale-up and applications in advanced therapeutic delivery.

Revolutionizing Therapeutic Delivery with Microneedle Technology for Tumor Treatment.

The tumor is an uncontrolled growth of tissue that can be localized (benign) or possesses the capability of metastasis (malignant). The conventional methods of tumor diagnosis, such as acupuncture, endoscopy, and histopathology, and treatment methods, such as injections, chemotherapy, surgery, and radiotherapy, are invasive, expensive, and pose severe safety and management issues for the patients. Microneedle technology is a recently developed approach for active transdermal drug delivery. It is minimally invasive, self-administrable, bypasses the first-pass effect, and effectively delivers chemotherapeutics and drugs at low doses, thus, overcoming the drawbacks of conventional delivery systems. This review provides an idea of the types, materials utilized in the fabrication, and techniques used for the preparation of microneedles (MNs), as well as their application in tumor diagnosis and treatment. Additionally, emphasis is given to the case studies related to MNs-assisted tumor therapy, such as photothermal therapy, gene therapy, photodynamic therapy, chemotherapy, immunotherapy, and various combination therapies. MNs also serve as a tool for diagnosis by the bio-sampling of blood and interstitial skin fluid, as well as biosensing various cancer biomarkers. The combined therapy and diagnostics provide theranostic MNs for enhanced and personalized tumor therapy. The limitations and prospects of MNs development are also discussed.