Insights of biopolymeric blended formulations for diabetic wound healing.

Diabetic wounds (DWs) pose a significant health burden worldwide, with their management presenting numerous challenges. Biopolymeric formulations have recently gained attention as promising therapeutic approaches for diabetic wound healing. These formulations, composed of biocompatible and biodegradable polymers, offer unique properties such as controlled drug release, enhanced wound closure, and reduced scarring. In this review, we aim to provide a comprehensive overview of the current state of research and future prospects regarding the application of biopolymeric formulations for diabetic wound healing. The review begins by highlighting the underlying pathophysiology of DWs, including impaired angiogenesis, chronic inflammation, and compromised extracellular matrix (ECM) formation. It further explores the key characteristics of biopolymeric materials, such as their biocompatibility, biodegradability, and tunable physicochemical properties, which make them suitable for diabetic wound healing applications. The discussion further delves into the types of biopolymeric formulations utilized in the treatment of DWs. These include hydrogels, nanoparticles (NP), scaffolds, films, and dressings. Furthermore, the review addresses the challenges associated with biopolymeric formulations for diabetic wound healing. In conclusion, biopolymeric formulations present a promising avenue for diabetic wound healing. Their unique properties and versatility allow for tailored approaches to address the specific challenges associated with DWs. However, further research and developments are required to optimize their therapeutic efficacy, stability, manufacturing processes, and regulatory considerations. With continued advancements in biopolymeric formulations, the future holds great promise for improving the management and outcomes of DWs.

Nanomaterials in the Wound Healing Process: New Insights and Advancements.

Wounds, which are becoming more common as a result of traumas, surgery, burns, and chronic illnesses like diabetes, remain a critical medical problem. Infectious bacteria impact the healing process, particularly if its biofilm (biological films) leads to a prolonged effect. Nanomaterials have emerged as promising candidates in the field of wound healing due to their unique properties and versatile applications. New insights into the interactions between nanomaterials and wound microenvironments have shed light on the mechanisms underlying their therapeutic effects. However, a significantly minimal amount of research has been carried out to see if these nanomaterials significantly promote the wound healing process. In this review, we provided an outline of the various types of nanomaterials that have been studied for healing wounds and infection prevention. Overall, the utilization of nanomaterials in wound healing holds great promise and continues to evolve, providing new opportunities for the development of effective and efficient wound care therapies.

Stimuli responsiveness of recent biomacromolecular systems (concept to market): A review.

Stimuli responsive delivery systems, also known as smart/intelligent drug delivery systems, are specialized delivery vehicles designed to provide spatiotemporal control over drug release at target sites in various diseased conditions, including tumor, inflammation and many others. Recent advances in the design and development of a wide variety of stimuli-responsive (pH, redox, enzyme, temperature) materials have resulted in their widespread use in drug delivery and tissue engineering. The aim of this review is to provide an insight of recent nanoparticulate drug delivery systems including polymeric nanoparticles, dendrimers, lipid-based nanoparticles and the design of new polymer-drug conjugates (PDCs), with a major emphasis on natural along with synthetic commercial polymers used in their construction. Special focus has been placed on stimuli-responsive polymeric materials, their preparation methods, and the design of novel single and multiple stimuli-responsive materials that can provide controlled drug release in response a specific stimulus. These stimuli-sensitive drug nanoparticulate systems have exhibited varying degrees of substitution with enhanced in vitro/in vivo release. However, in an attempt to further increase drug release, new dual and multi-stimuli based natural polymeric nanocarriers have been investigated which respond to a mixture of two or more signals and are awaiting clinical trials. The translation of biopolymeric directed stimuli-sensitive drug delivery systems in clinic demands a thorough knowledge of its mechanism and drug release pattern in order to produce affordable and patient friendly products.

Chitosan in Oral Drug Delivery Formulations: A Review.

Nanoformulations have become increasingly useful as drug delivery technologies in recent decades. As therapeutics, oral administration is the most common delivery method, although it is not always the most effective route because of challenges with swallowing, gastrointestinal discomfort, low solubility, and poor absorption. One of the most significant barriers that medications must overcome to exert a therapeutic effect is the impact of the first hepatic transit. Studies have shown that controlled-release systems using nanoparticles composed of biodegradable natural polymers significantly improve oral administration, which is why these materials have attracted significant attention. Chitosan possesses a wide variety of properties and functions in the pharmaceutical as well as healthcare industries. Drug encapsulation and transport within the body are two of its most important features. Moreover, chitosan can enhance drug efficacy by facilitating drug interaction with target cells. Based on its physicochemical properties, chitosan can potentially be synthesized into nanoparticles, and this review summarizes recent advances and applications of orally delivered chitosan nanoparticle interventions.

Phytoconstituent-Loaded Nanofibrous Meshes as Wound Dressings: A Concise Review.

In the past, wounds were treated with natural materials, but modern wound dressings include functional elements to expedite the process of healing and to improve skin recovery. Due to their exceptional properties, nanofibrous wound dressings are now the most cutting-edge and desirable option. Similar in structure to the skin's own extracellular matrix (ECM), these dressings can promote tissue regeneration, wound fluid transportation, and air ductility for cellular proliferation and regeneration owing to their nanostructured fibrous meshes or scaffolds. Many academic search engines and databases, such as Google Scholar, PubMed, and Sciencedirect, were used to conduct a comprehensive evaluation of the literature for the purposes of this investigation. Using the term "nanofibrous meshes" as a keyword, this paper focuses on the importance of phytoconstituents. This review article summarizes the most recent developments and conclusions from studies on bioactive nanofibrous wound dressings infused with medicinal plants. Several wound-healing methods, wound-dressing materials, and wound-healing components derived from medicinal plants were also discussed.

A propitious role of marine sourced polysaccharides: Drug delivery and biomedical applications.

Numerous compounds, with extensive applications in biomedical and biotechnological fields, are present in the oceans, which serve as a prime renewable source of natural substances, further promoting the development of novel medical systems and devices. Polysaccharides are present in the marine ecosystem in abundance, promoting minimal extraction costs, in addition to their solubility in extraction media, and an aqueous solvent, along with their interactions with biological compounds. Certain algae-derived polysaccharides include fucoidan, alginate, and carrageenan, while animal-derived polysaccharides comprise hyaluronan, chitosan and many others. Furthermore, these compounds can be modified to facilitate their processing into multiple shapes and sizes, as well as exhibit response dependence to external conditions like temperature and pH. All these properties have promoted the use of these biomaterials as raw materials for the development of drug delivery carrier systems (hydrogels, particles, capsules). The present review enlightens marine polysaccharides providing its sources, structures, biological properties, and its biomedical applications. In addition to this, their role as nanomaterials is also portrayed by the authors, along with the methods employed to develop them and associated biological and physicochemical properties designed to develop suitable drug delivery systems.

Natural product-based pharmacological studies for neurological disorders.

Central nervous system (CNS) disorders and diseases are expected to rise sharply in the coming years, partly because of the world's aging population. Medicines for the treatment of the CNS have not been successfully made. Inadequate knowledge about the brain, pharmacokinetic and dynamic errors in preclinical studies, challenges with clinical trial design, complexity and variety of human brain illnesses, and variations in species are some potential scenarios. Neurodegenerative diseases (NDDs) are multifaceted and lack identifiable etiological components, and the drugs developed to treat them did not meet the requirements of those who anticipated treatments. Therefore, there is a great demand for safe and effective natural therapeutic adjuvants. For the treatment of NDDs and other memory-related problems, many herbal and natural items have been used in the Ayurvedic medical system. Anxiety, depression, Parkinson's, and Alzheimer's diseases (AD), as well as a plethora of other neuropsychiatric disorders, may benefit from the use of plant and food-derived chemicals that have antidepressant or antiepileptic properties. We have summarized the present level of knowledge about natural products based on topological evidence, bioinformatics analysis, and translational research in this review. We have also highlighted some clinical research or investigation that will help us select natural products for the treatment of neurological conditions. In the present review, we have explored the potential efficacy of phytoconstituents against neurological diseases. Various evidence-based studies and extensive recent investigations have been included, which will help pharmacologists reduce the progression of neuronal disease.

A Comprehensive Review on Nutraceuticals: Therapy Support and Formulation Challenges.

Nutraceuticals are the nourishing components (hybrid of nutrition and pharmaceuticals) that are biologically active and possess capability for maintaining optimal health and benefits. These products play a significant role in human health care and its endurance, most importantly for the future therapeutic development. Nutraceuticals have received recognition due to their nutritional benefits along with therapeutic effects and safety profile. Nutraceuticals are globally growing in the field of services such as health care promotion, disease reduction, etc. Various drug nutraceutical interactions have also been elaborated with various examples in this review. Several patents on nutraceuticals in agricultural applications and in various diseases have been stated in the last section of review, which confirms the exponential growth of nutraceuticals' market value. Nutraceuticals have been used not only for nutrition but also as a support therapy for the prevention and treatment of various diseases, such as to reduce side effects of cancer chemotherapy and radiotherapy. Diverse novel nanoformulation approaches tend to overcome challenges involved in formulation development of nutraceuticals. Prior information on various interactions with drugs may help in preventing any deleterious effects of nutraceuticals products. Nanotechnology also leads to the generation of micronized dietary products and other nutraceutical supplements with improved health benefits. In this review article, the latest key findings (clinical studies) on nutraceuticals that show the therapeutic action of nutraceutical's bioactive molecules on various diseases have also been discussed.

Antibody drug conjugates in gastrointestinal cancer: From lab to clinical development.

The antibody-drug conjugates (ADCs) are one the fastest growing biotherapeutics in oncology and are still in their infancy in gastrointestinal (GI) cancer for clinical applications to improve patient survival. The ADC based approach is developed with tumor specific antigen, antibody carrying cytotoxic agents to precisely target and deliver chemotherapeutics at the tumor site. To date, 11 ADCs have been approved by US-FDA, and more than 80 are in the clinical development phase for different oncological indications. However, The ADCs based therapies in GI cancers are still far from having high-efficient clinical outcomes. The limited success of these ADCs and lessons learned from the past are now being used to develop a newer generation of ADC against GI cancers. In this review, we did a comprehensive assessment of the key components of ADCs, including tumor marker, antibody, cytotoxic payload, and linkage strategy, with a focus on technical improvement and some future trends in the pipeline for clinical translation. The various preclinical and clinical ADCs used in gastrointestinal malignancies, their target, composition and bioconjugation, along with preclinical and clinical outcomes, are discussed. The emphasis is also given to new generation ADCs employing novel mAb, payload, linker, and bioconjugation methods are also included.

Design, synthesis and comparative analysis of triphenyl-1,2,3-triazoles as anti-proliferative agents.

Herein, a series of triaryl-1,2,3-triazoles, in order to check cytotoxicity on breast cancer cell lines have been synthesized with pendent benzyl ring to mimic the phenolic A ring of Tamoxifene. The biological results indicated that most of the compounds possessed comparative anti-proliferative activities in both ER + ve (MCF-7) and ER-ve (MDA-MB-231) breast cancer cell lines. Among synthesized derivatives, five compounds 8f, 8i, 8j, 8n and 8p showed anti-proliferative activities at <5 µM against MCF-7 cell line and three compounds 8e, 8f and 8j show IC50 value greater than 30 µM in FR-2 cells (normal cell). Moreover, to understand the mechanistic behavior of the selective compound 8f, various studies performed viz. surface morphological changes by bright field microscopic examination, nuclear morphological alteration by DAPI staining, measurement of intracellular ROS level and determination of change in mitochondrial membrane potential. It was observed that, the selective compound 8f associated with higher ROS generation along with decrease in mitochondrial membrane potential in addition to surface and nuclear morphological alterations such as reduction in number and shrinkage of cells coupled with nuclear blabbing indicating sign of apoptosis. Further, molecular docking study in comparison to tamoxifen was also carried out to investigate the interaction of 8f with ER-α which favors its possible mode of anticancer action.

Andrographolide: Chemical modification and its effect on biological activities.

The major natural bioactive constituent of Andrographis paniculata (AP) (Burm. f.) Nees Andrographolide (1) and its derivatives are well acknowledged in literature for its biological activities such as anti-cancer, anti-diabetic, anti-inflammatory, anti-bacterial, anti-malarial, antihepatitis, anti-HIV, anti-atherosclerosis, hepatoprotective, FXR antagonist, and α-glucosidase inhibition. Many reports are available related to Andrographolide (1) but a consolidated review on the chemical modification of andrographolide with special emphasis on its different functional groups with respect to their biological activities is still missing from the previous literature. Therefore, herein we have collected a literature for the period 2009 onwards in relation to chemistry on andrographolide (1) and its effect on respective biological activity. Also, special attempt on increasing the bioavailability of andrographolide (1) has been given for the designing of various targeted drug delivery systems.

BCl3-Mediated C-N, C-S, and C-O Bond Formation of Imidazo[1,2-a]pyridine Benzylic Ethers.

An efficient BCl3-mediated reaction of imidazo[1,2-a]pyridines has been developed for the C-N, C-S, and C-O bond formation. The salient features of this method correspond to the substitution of different nucleophiles via in situ unconventional debenzylation. The developed process is applicable for the synthesis of a wide variety of ((3-amino/thio/alkoxy)-methyl)-imidazo[1,2-a]pyridines.

Cathepsin-sensitive nanoscale drug delivery systems for cancer therapy and other diseases.

Cathepsins are an important category of enzymes that have attracted great attention for the delivery of drugs to improve the therapeutic outcome of a broad range of nanoscale drug delivery systems. These proteases can be utilized for instance through actuation of polymer-drug conjugates (e.g., triggering the drug release) to bypass limitations of many drug candidates. A substantial amount of work has been witnessed in the design and the evaluation of Cathepsin-sensitive drug delivery systems, especially based on the tetra-peptide sequence (Gly-Phe-Leu-Gly, GFLG) which has been extensively used as a spacer that can be cleaved in the presence of Cathepsin B. This Review Article will give an in-depth overview of the design and the biological evaluation of Cathepsin-sensitive drug delivery systems and their application in different pathologies including cancer before discussing Cathepsin B-cleavable prodrugs under clinical trials.

Hyaluronic Acid-Tacrolimus Bioconjugate: Synthesis, Characterization, and Pharmacokinetic Investigation of an Acid-Responsive Macromolecular Prodrug.

Polymer-drug conjugates have been the cornerstone of several drug delivery systems owing to their numerous benefits such as improved drug solubilization, controlled release, increased efficacy, and improved pharmacokinetics. Herein, an acid-responsive macromolecular prodrug was synthesized by conjugation of Tacrolimus (TAC; FK506) with chemically modified hyaluronic acid (HA), and its physicochemical and pharmacokinetic properties were studied in detail. The prepared conjugate (HA-ADH-TAC) showed 1% drug loading, sustained drug release, and significantly enhanced solubility for the investigated drug. Additionally, cellular uptake study indicated augmented uptake of this conjugate, and hemolysis assay showed biocompatibility of the developed prodrug. Further, the pharmacokinetic behavior of the conjugate was investigated, and it was observed that pharmacokinetic parameters with the conjugate were improved. The results indicate that the developed HA-tacrolimus conjugate has the edge over the plain drug in terms of improved physicochemical properties and favorable pharmacokinetic response.

Tacrolimus: An updated review on delivering strategies for multifarious diseases.

From the current trends, tacrolimus (TAC) has become an important therapeutic option for the optimal individualization of immunosuppressive therapy especially in case of transplant recipients. TAC is used most frequently in comparison to other immunosuppressants because it offers better safety profile with increased long-term survival in patients especially in children and adolescents. This drug has developed an immense interest in the research field owing to its potential pharmacological scope but due to its poor water solubility, need of concomitant steroids and higher incidences of nephrotoxicity, there comes a need for future research to minimize such limitations and decipher maximum use of the drug. In addition, there are number of formulations attempted to enhance its erratic bioavailability through various techniques namely solid dispersions, inclusion complexes, prodrug approach, SMEDDS etc. The present review aims to acknowledge the TAC pharmacokinetic profile and novel drug delivery systems in multiple diseased conditions by particularly enhancing its poor biopharmaceutical issues as well as dose related toxicity. Collectively, we have updated the data pertaining to the drug delivery prospects of TAC for the period of last 8-10years.

Medicinal attributes of 1,2,3-triazoles: Current developments.

1,2,3-Triazoles are important five-membered heterocyclic scaffold due to their extensive biological activities. This framework can be readily obtained in good to excellent yields on the multigram scale through click chemistry via reaction of aryl/alkyl halides, alkynes and NaN3 under ambient conditions. It has been an emerging area of interest for many researchers throughout the globe owing to its immense pharmacological scope. The present work aims to summarize the current approaches adopted for the synthesis of the 1,2,3-triazole and medicinal significance of these architectures as a lead structure for the discovery of drug molecules such as COX-1/COX-2 inhibitors (celecoxib, pyrazofurin), HIV protease inhibitors, CB1 cannabinoid receptor antagonist and much more which are in the pipeline of clinical trials. The emphasis has been given on the major advancements in the medicinal prospectus of this pharmacophore for the period during 2008-2016.

Polysaccharides based nanomaterials for targeted anti-cancer drug delivery.

Polysaccharides, an important class of biological polymers, are effectively bioactive, nontoxic, hydrophilic, biodegradable and offer a wide diversity in structure and properties. These can be easily modified chemically and biochemically to enhance the bioadhesion with biological tissues, better stability and can improve bioavailability of drugs. Most of the chemotherapeutic drugs have a narrow therapeutic index, slow drug delivery systems and poor water solubility that usually proves toxic to human bodies. The inherent biocompatibility of these biopolymers have shown enhancement of solubility of some chemotherapeutic drugs which also leads to the preparation of nanomaterials for the delivery of antibiotics, anticancer, proteins, peptides and nucleic acids using several routes of administration. Recently, synthesis and research on polysaccharides based nanomaterials have gained enormous attention as one of the most applicable resources in nanomedicine area. This review article will provide a specific emphasis on polysaccharides as natural biomaterials for targeted anticancer drug delivery system.