Nanobiocatalysis: Approach and Applications in Drug Development and Sensing.

Enzymes play a pivotal role in the human body, but their potential is not limited to just that. Scientists have successfully modified these enzymes as nanobiocatalysts or nanozymes for industrial or commercial use, either in the food, medicine, biotech or even textile industries. These nanobiocatalysts and nanozymes offer several advantages over enzymes, like better stability, improved shelf-life, increased percentage yield, and reuse potential, which is very difficult with normal enzymes. The various techniques of NBC synthesis using immobilization techniques like adsorption, covalent binding, affinity immobilization, and entrapment methods are briefly discussed. The enzymes are either entrapped or adsorbed on the nanocarrier matrices, which can be nanofibers, nanoporous carriers, or nanocontainers as nanobiocatalysts. We also highlight the challenges the nanobiocatalyst overcomes in the industrial production of some drugs like sitagliptin, montelukast, pregabalin, and atorvastatin. Also, the inactivation of an organophosphate or opioid poisoning treating agent, SSOPOX nanohybrid, is discussed in this paper. Nanozymes are intrinsic enzyme-like compounds, and they also show wide application in themselves. Their GQD/AGNP nanohybrid shows antibacterial potential; they can also be utilized in optical sensing to detect small molecules, ions, nucleic acids, proteins, and cancer cells. In this paper, various applications of these NBCs have been discussed, and their potential applications with examples are also mentioned. Nanoenzymes can address targeted drug delivery via the controlled release of drugs to increase the efficacy of anticancer drugs that minimize damage to healthy tissue or cells.

Unlocking Antioxidant-Anticancer Synergy: An Exploration of Therapeutic Bioactives from Methanolic Extracts of Rubus ellipticus and Boerhavia diffusa Using HeLa Cell Line.

This study aimed to assess the synergistic antioxidant and anticancer effects of methanolic extracts derived from Rubus ellipticus and Boerhavia diffusa fruits against the HeLa cell line. The methanolic extracts were prepared from the fruits of R. ellipticus and B. diffusa, and their antioxidant potential was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity assay and the ferric reducing antioxidant power (FRAP) assay. The anticancer effects of benzoic acid and rutin extracted from the aforementioned fruits were also investigated against the HeLa cell line using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay to measure the cell metabolic activity. Using Synergy Finder plus software, the bioactive compounds were tested to explore any synergistic effects. R. ellipticus exhibited higher antioxidant potential as revealed by higher DPPH scavenging activity and FRAP value compared with B. diffusa. The benzoic acid extracted from R. ellipticus demonstrated potent anticancer activity against the HeLa cell line, with an IC50 of 1.07 µg/mL. Similarly, rutin extracted from B. diffusa displayed moderate anticancer activity with an IC50 of 1.4 µg/mL while exhibiting minimal impact on normal cell lines. The combination studies of the extracted bioactive compounds revealed a synergistic effect. These findings suggest the therapeutic potential of R. ellipticus and B. diffusa in combating the oxidative stress and cancer. Their bioactive compounds like benzoic acid and rutin were observed to act synergistically. Further investigations are warranted to elucidate the underlying mechanisms and evaluate their applicability in clinical settings.

Latest Delivery Advancements of Lipid Nanoparticles for Cancer Treatment.

As one of the primary causes of illness and death globally, cancer demands novel and potent treatment approaches, which is why lipid nanoparticles (LNPs) have gained attention as a promising delivery system for anticancer drugs with precision and efficacy. The article discusses the salient characteristics of LNPs, such as the lipid components, particle size, polydispersity index, and encapsulation efficiency, followed by strategies that enhance their remarkable drug delivery capabilities. The articles explore LNPs ability to improve the solubility, stability, and bioavailability of various chemotherapeutics, nucleic acids, and immunotherapeutic modalities. It also highlights the recent advancement in surface modification of LNPs, which is essential to improve their effectiveness. Tailored coatings of LNPs improve targeting precision, stability, and biocompatibility; enhancing their transport to boost therapeutic efficacy for cancer targeting. The review summarizes the recent advancements made in using LNPs to treat different forms of cancer and focuses on the most recent clinical studies. Overall, the review highlights that the LNPs can target and treat cancer in a tailored manner through gene therapy, RNA interference, and immunotherapy.

Regulatory landscape and challenges in CAR-T cell therapy development in the US, EU, Japan, and India.

Chimeric Antigen Receptor-T cell (CAR-T) therapy has evolved as a revolutionary cancer treatment modality, offering remarkable clinical responses by harnessing the power of a patient's immune system to target and eliminate cancer cells. However, the development and commercialization of CAR-T cell therapies are accompanied by complex regulatory requirements and challenges. This therapy falls under the regulatory category of advanced therapy medicinal products. The regulatory framework and approval tools of regenerative medicine, especially CAR-T cell therapies, vary globally. The present work comprehensively analyses the regulatory landscape and challenges in CAR-T cell therapy development in four key regions: the United States, the European Union, Japan, and India. This work explores the unique requirements and considerations for preclinical studies, clinical trial design, manufacturing standards, safety evaluation, and post-marketing surveillance in each jurisdiction. Due to their complex nature, developers and manufacturers face several challenges. In India, despite advancements in treatment protocols and government-sponsorships, there are still several difficulties regarding access to treatment for the increasing number of cancer patients. However, India's first indigenously developed CAR-T cell therapy, NexCAR19, for B-cell lymphoma or leukemia, approved and available at a low cost compared to other available CAR-T therapies, raises great hope in the battle against cancer. Several strategies are proposed to address the identified hurdles from global and Indian perspectives. It discusses the benefits of aligning regulatory requirements across regions, eventually facilitating international development and enabling access to this transformative therapy.

Pulmonary Fibrosis: Unveiling the Pathogenesis, Exploring Therapeutic Targets, and Advancements in Drug Delivery Strategies.

Idiopathic pulmonary fibrosis (IPF) is an ailment with no cure and a very high rate of progression that ultimately leads to death. The exact reason for this disease is still not acknowledged. Many underlying mechanisms of wound healing and various types of stimuli that trigger the pathogenesis of IPF continue to be intensively explored. The exact therapy for the reversal of this disease is not yet known and is constantly in progress. Existing treatments only slow down the process or mitigate the symptoms to enhance the patient's healthcare system. The only two Food and Drug Administration-approved oral medications include pirfenidone and nintedanib whose high dose and systemic circulation can have side effects to a greater extent. Further research on restorative and extra-curative therapies for IPF is necessary due to the absence of viable therapeutic choices. To assure minimum off-targeted site delivery and longer duration of action, techniques that offer a sustainable release of the drug, better bioavailability, and patient compliance can be used.The work is an overview of the main therapeutic targets and pertinent developing therapies for the management of IPF. This study is an attempt to focus on various drug delivery systems that are responsible for showing effectiveness in defense mechanisms against IPF.

The electronic tongue: an advanced taste-sensing multichannel sensory tool with global selectivity for application in the pharmaceutical and food industry.

Taste is a crucial organoleptic characteristic that determines whether a substance will be accepted for delivery through the mouth. However, the vast majority of medications have an unpleasant taste. Drugs with a bitter taste are often depicted using a variety of flavouring compounds to increase patient acceptance and compliance. Human panellists are the principal means of assessing the flavour of medication ingredients and formulations. Due to the toxicity of medications and subjectivity of taste panellists, as well as issues with hiring taste panellists and panel upkeep when working with unpleasant items, the use of sensory panellists in the industry is particularly challenging and troublesome. Furthermore, tests cannot be conducted on compounds that have not received FDA approval. As a result, the analytical taste-sensing multichannel sensory system known as the electronic tongue (also known as the artificial tongue or e-tongue) helps in reducing the number of samples that are ought to be assessed by trained sensory panels and also when the sample to be tasted is injurious or harmful for the concerned person. Therefore, e-tongue has advantages like lowering reliance on human panels. The working theory, the sensors used, and the pharmaceutical and food applications are covered, along with the major software used, difficulties, and future scope are also highlighted.

Recent Advances and Prospects for Plant Gum-Based Drug Delivery Systems: A Comprehensive Review.

This work is an effort to first introduce plant-based gums and discussing their drug delivery applications. The composition of these plant gums and their major characteristics, which make them suitable as pharmaceutical excipients are also described in detail. The various modifications methods such as physical and chemical modifications of gums and polysaccharides have been discussed along with their applications in different fields. Consequently, plant-based gums modification such as etherification and grafting is attracting much scientific attention to satisfy industrial demand. The evaluation tests to characterize gum-based drug delivery systems have been summarized. The release behavior of drug from plant-gum-based drug delivery is being discussed. Thus, this review is an attempt to critically summarize different aspect of plant-gum-based polysaccharides to be utilized in drug delivery systems having potential industrial applications.

The Role of Polymers and Excipients for Better Gastric Retention of Captopril.

Captopril is an angiotensin-converting enzyme (ACE) inhibitor that prevents angiotensin I (ATI) from being converted to angiotensin II (ATII). However, it offers certain limitations like instability, dose dumping and burst release due to its usage in the native state. In the last two decades, different polymers and excipients have been used to make captopril more accessible and well-accepted. The present work discusses the efforts made by various scientists so far to make the oral administration of captopril more acceptable by overcoming its limitations. The different factors affecting gastric retention, approaches to achieve better gastric retention. The oral managed release dosage forms have enormous curative benefits such as improved therapeutics and better patient compliance. The polymer based gastro-retentive drug delivery systems (GRDDS) include microspheres, soild inclusion complex, floating tablets, alginate based beads, etc utilizes better retention in the stomach for longer duration of action and improved bioavailability. Overall, the work aims to summarize the attempts made as novel drug delivery approaches over the last two decades in reverse chronological order to make captopril more gastro retentive and orally acceptable by the patients.

Getting into the Brain: Are We in Yet or Just Knocking at the Door?

Nanomedicine, a promising addition to the spectrum of biomedicine, has viewed countless breakthroughs in the implementations of "site-specific" drug delivery. The promises of nanomedicines revolve around their unique physicochemical properties that permit the transport of therapeutics to the desired site of action, improve the pharmacokinetic endpoint, maximize the pharmacological influence of treatment, and overcome the limitation of remedies that otherwise would impede the therapeutic effectiveness. One of most insurmountable challenge possessed by conventional drug-delivery in getting therapeutics across the central-nervous-system is to conquer the harsh passage of the blood-brain barrier (BBB). Many published studies revealed BBB to be a complex, dynamic interface that acclimatizes to the needs of the central nervous system (CNS). These physical and biochemical barriers pose a significant challenge to the effective management of brain-related disorders such as neurodegenerative diseases. This challenge is widely accepted and defeated with the advent of a new class of brain-targeted nanomedicines. This review is an effort to overview the key research trends in nanotechnology over the past decade concerning the BBB as a regulatory interface and factors affecting CNS drug delivery. The review further summarized the specific diversity of various nanomedicinal approaches, the critical and elementary structural component of their design, the surface engineering of vehicles carrying drug at the nanoscale, selected current clinical successes, and future prospects along with hidden perils.

Nanomedicine-Based Delivery Strategies for Breast Cancer Treatment and Management.

Breast cancer is one of the most common types of cancer among women globally. It is caused by mutations in the estrogen/progesterone receptors and conventional treatment methods are commonly utilized. About 70-80 percent of individuals with the early-stage non-metastatic disease may be cured. Conventional treatment is far less than the optimal ratio, as demonstrated through the high mortality rate of women with this cancer. However, conventional treatment methods like surgery, radiotherapy, and chemotherapy are not as effective as expected and lead to concerns about low bioavailability, low cellular uptake, emerging resistance, and adverse toxicities. A nanomedicine-based approach is a promising alternative for breast cancer treatment. The present era is witnessing rapid advancements in nanomedicine as a platform for investigating novel therapeutic applications and modern intelligent healthcare management strategies. This paper focuses on nanomedicine-based therapeutic interventions that are becoming more widely accepted for improving treatment effectiveness and reducing undesired side effects in breast cancer patients. By evaluating the state-of-the-art tools and taking the challenges involved into consideration, various aspects of the proposed nano-enabled therapeutic approaches have been discussed in this review.

COVID-19 associated rhino-orbital-cerebral mucormycosis-an institutional series.

Mucormycosis is almost always confined to the patients with altered host defenses amongst which diabetes is considered as the strongest risk factor. COVID-19 only been seen in severe cases but also in mild and moderate cases of SARS-CoV-2 infections. After preliminary clinical and radiological diagnosis, surgical management in the form of endoscopic sinus surgery, debridement, and orbital exenteration (8) was performed. Medical management in the form of antifungal therapy (amphotericin-B, posaconazole, and isavuconazole) was initiated. In this case series, 79 proven cases of COVID-19 associated rhino-orbital-cerebral mucormycosis were analyzed retrospectively from mid-April 2021 to mid-September 2021. 67 patients were known diabetics, whereas rest 12 had new onset diabetes mellitus. Of these 79 cases, 27 cases had the disease limited to sinuses (rhino-mucormycosis), 43 had orbital involvement also (rhino-orbital mucormycosis), and 9 had cerebral involvement as well (rhino-orbital-cerebral mucormycosis). During this time-period, a total of 14 mortalities occurred. Most of the patients were discharged after completion of amphotericin-B therapy and rest stayed little longer till their general condition improved. COVID-19 causes dysregulation and alteration of immune response in the body which predispose to invasive fungal infections. In addition, uncontrolled diabetes mellitus and corticosteroid treatment increase the risk of mucormycosis by many folds.

A Critical Review on Floating Tablets as a Tool for Achieving Better Gastric Retention.

Most of the oral drug delivery systems demand better retention of drug in the gastrointestinal tract (GIT) for better bioavailability. One of the tools for better gastric retention of the drug is to administer it as a floating drug delivery system (FDDS) by reducing its density, compared to the gastric fluids. This system is helpful to overcome the problems associated with the conventional pharmaceutical dosage forms. The present work is an effort to systematically review the latest advancements in FDDS with a major spotlight on how these systems act to make the dosage form float in the gastric fluid for the slow release, better gastric retention, and improved bioavailability of the orally administered drug. As managing diseases through medicines is going in a new age in which innovative delivery system is being used as well as made accessible for remedial use. The excipients used for making such oral gastro-retention dosage forms (GRDF) to provide sustained release profile of drugs along with the work done so far by different scientists in the past two decades; the patents filed in this area; the evaluation methods for checking the quality of FDDS; and their applications are the major highlights of this work.

Ellagic acid-loaded, tween 80-coated, chitosan nanoparticles as a promising therapeutic approach against breast cancer: In-vitro and in-vivo study.

AIMS: Among polyphenolic phytoconstituents with anticancer properties, Ellagic acid (EA) is widely reported for its translational potential in vitro but efficient in vivo delivery of EA has been a challenge. We, for the first time, used a tween 80 coated nano delivery of Ellagic acid to evaluate its preclinical efficacy in vitro and in vivo for breast cancer. MAIN METHODS: To overcome the challenges of in vivo delivery, two batches of chitosan-based nanoformulations of EA (with and without tween 80 coating) were prepared by the ionotropic gelation method. The nanoformulations were characterized and further evaluated in vitro against breast cancer cells (MCF7) and in vivo with EAC tumor-bearing mice for establishing their anticancer efficacy compared to Ellagic acid alone. A quantitative simulation study was undertaken to understand if the observed antitumor efficacy is due to the synergistic efficacy of the Chitosan-Ellagic acid combination. KEY FINDINGS: Results revealed that nanoformulations consist of good nano-sized encapsulation of EA and showed good drug entrapment-release capacity. Nano-encapsulated EA is biocompatible and exhibited higher cytotoxicity in vitro compared to EA alone. Similarly, significantly higher tumor regression was observed in nano-EA treated mice compared to EA alone, and best efficacy was observed with the nanoformulation with tween 80 coating. Furthermore, nanoformulations showed higher apoptosis in tumor tissues with no significant tissue toxicity in vital organs. SIGNIFICANCE: We report synergism of Chitosan-Ellagic acid combination in the tween 80 coated nanoparticles of Ellagic acid resulting in enhanced anti-breast tumor efficacy that may be of translational value for other tumor types, too.

Critical Reviews on Pediatric Dosage Form Developments and Medical Devices.

The pediatric population is generally considered as "miniature adults," but they actually differ from adults due to their different body compositions and varied stages of organ development, which alter essential biopharmaceutical parameters. The physiological differences between the pediatric population and the adult population alter the essential kinetics and dynamics of the same drug administered at the same dose. For pediatric patients, the drug dose is generally calculated using different formulas based on age, body surface area, or weight, or is simply reduced to half of adult dose. This, however, is not the correct practice. New approaches have emerged for designing customized formulations and medical devices for the pediatric population. Examples of customized formulations are "mini-tablets" and "oro-dispersible films," which attempt to ease the administration of solid oral dosage forms. These specially designed medical devices have shown the ability to overcome many challenges in dose administration to children. One such medical device is the "oral solid dosage pen," which allows for dose adjustment by cutting a tablet-like drug carrier at a predefined height and offers flexibility and convenience for dose administration to the pediatric population. Other medical devices, such as the Nipple Shield Delivery System (NSDS) and Medibottle also aid in efficient drug delivery to pediatrics. This review summarizes the challenges in dosage form design and advances in suitable medical devices for better administration to the pediatric population to overcome accidents due to medical errors, incomplete absorption, and toxicity.

Emerging Pathophysiological Targets of Psoriasis for Future Therapeutic Strategies.

Psoriasis is a chronic autoimmune skin disorder which involves complex interactions between genes, keratinocytes, T-cells and inflammatory cells. It affects 2-3% population worldwide. Molecular biology and cellular immunology of psoriasis, when linked with biotechnology and genetic studies can help researchers to understand the pathophysiology of psoriasis. T-cells activation, keratinocyte hyperproliferation, and angiogenesis are the core mechanisms entailed in the development of psoriasis lesion. Investigators are trying to overcome the challenges of complex pathophysiology pathways involved in this disorder. The different possible hypotheses for its pathophysiology such as growth factors, enzymes, inflammation, and genetic factors mediated pathophysiology have been described in the present review paper in detail. Clinically available drugs only control the symptoms of psoriasis but are not effective for the treatment of the disorder completely and are also associated with some side effects such as itching, renal disorders, hematologic, nonmelanoma skin cancer, pulmonary, gastrointestinal toxicity, etc. This paper made an effort to understand the pathophysiological targets, discuss the research done so far and the treatments available for the effective management of psoriasis.

Dendrimers for Therapeutic Delivery: Compositions, Characterizations, and Current Status.

Dendrimers, commonly referred to as arborols, offer tremendous opportunities for drug delivery, diagnostics, and treatment applications. This may be attributed to the characteristic features of their three architectural components: core, branches, and terminal groups. These components provide vast flexibility to designers. They act as highly moldable platforms that can be modified to suit the needs of application designers. Effectively, the type, length, and molecular weight of the core, branches and terminal groups may be customized to achieve desired characteristics and satisfy the demands of numerous applications. These perfectly designed multifunctional structures are reviewed in the current paper, focusing on their complex archetypical design for interphase applications; novel drug delivery applications, especially oral, ocular, pulmonary, transdermal; targeted, and controlled-release; and diagnosis and treatment of diseases like cancer, diabetes, and autoimmune disorders.

Dendritic platforms for biomimicry and biotechnological applications.

Dendrimers, commonly referred to as polymeric trees, offer endless opportunities for biotechnological and biomedical applications. By controlling the type, length, and molecular weight of the core, branches and end groups, respectively, the chemical functionality and topology of dendrimeric archetypes can be customized which further can be applied to achieve required solubility, biodegradability, diagnosis and other applications. Given the physicochemical variability of the dendrimers and their hybrids, this review attempts to discuss a full spectrum of recent advances and strides made by these "perfectly designed structures". An extensive biotech/biomimicry application profiling of dendrimers is provided with focus on complex archetypical designs such as protein biomimicry (angiogenic inhibitors, regenerative hydroxyapatite and collagen) and biotechnology applications. In terms of biotechnological advances, dendrimers have provided distinctive advantages in the fields of biocatalysis, microbicides, artificial lights, mitochondrial function modulation, vaccines, tissue regeneration and repair, antigen carriers and even biosensors. In addition, this review provides overview of the extensive chemo-functionalization opportunities available with dendrimers which makes them a perfect candidate for forming drug conjugates, protein hybrids, bio mimics, lipidic derivatives, metal deposits and nanoconjugates thereby making them the most multifunctional platforms for diverse biotechnological applications.

Anti-inflammatory, Analgesic and Antiulcer properties of Porphyra vietnamensis.

OBJECTIVES: Aim of the present work was to investigate the anti-inflammatory, analgesic and antiulcer effects of red seaweed Porphyra vietnamensis (P. vietnamenis). MATERIALS AND METHODS: Aqueous (POR) and alcoholic (PE) fractions were successfully isolated from P. vietnamenis. Further biological investigations were performed using a classic test of paw edema induced by carrageenan, writhing induced by acetic acid, hot plate method and naproxen induced gastro-duodenal ulcer. RESULTS: Among the fractions POR showed better activity. POR and PE significantly (p < 0.05) reduced carrageenan induced paw edema in a dose dependent manner. In the writhing test POR significantly (p < 0.05) reduced abdominal writhes than PE. In hot plate method POR showed better analgesic activity than PE. POR showed comparable ulcers reducing potential (p<0.01) to that of omeprazole, and has more ulcer reducing potential then PE. CONCLUSIONS: The results of this study demonstrated that P. vietnamenis aqueous fraction possesses biological activity that is close to the standards taken for the treatment of peripheral painful or/and inflammatory and ulcer conditions.

Minocycline encapsulated chitosan nanoparticles for central antinociceptive activity.

The purpose of the study is to explore the central anti-nociceptive activity of brain targeted nanoparticles (NP) of minocycline hydrochloride (MH). The NP were formulated using the modified ionotropic gelation method (MHNP) and were coated with Tween 80 (T80) to target them to brain (cMHNP). The formulated nanoparticles have already been characterized for particle size, zeta potential, drug entrapment efficiency and in vitro drug release. The nanoparticles were then evaluated for pharmacodynamic activity using thermal methods. The pure drug and the formulation, MHNP were not able to show a statistically significant central analgesic activity. cMHNP on the other hand evidenced a significant central analgesic activity. Animal models evidenced that brain targeted nanoparticles may be utilized for effective delivery of central anti-nociceptive effect of MH. Further clinical studies are required to explore the activity for mankind.

Significance of algal polymer in designing amphotericin B nanoparticles.

Development of oral amphotericin B (AmB) loaded nanoparticles (NPs) demands a novel technique which reduces its toxicity and other associated problems. Packing of AmB in between two oppositely charged ions by polyelectrolyte complexation technique proved to be a successful strategy. We have developed a novel carrier system in form of polyelectrolyte complex of AmB by using chitosan (CS) and porphyran (POR) as two oppositely charged polymers with TPP as a crosslinking agent. Initially POR was isolated from Porphyra vietnamensis followed by the fact that its alkali induced safe reduction in molecular weight was achieved. Formulation was optimized using three-factor three-level (3(3)) central composite design. High concentration of POR in NPs was confirmed by sulfated polysaccharide (SP) assay. Degradation and dissolution studies suggested the stability of NPs over wide pH range. Hemolytic toxicity data suggested the safety of prepared formulation. In vivo and in vitro antifungal activity demonstrated the high antifungal potential of optimized formulation when compared with standard drug and marketed formulations. Throughout the study TPP addition did not cause any significant changes. Therefore, these experimental oral NPs may represent an interesting carrier system for the delivery of AmB.