A comprehensive review of the application of 3D-bioprinting in chronic wound management.

INTRODUCTION: Chronic wounds require more sophisticated care than standard wound care because they are becoming more severe as a result of diseases like diabetes. By resolving shortcomings in existing methods, 3D-bioprinting offers a viable path toward personalized, mechanically strong, and cell-stimulating wound dressings. AREAS COVERED: This review highlights the drawbacks of traditional approaches while navigating the difficulties of managing chronic wounds. The conversation revolves around employing natural biomaterials for customized dressings, with a particular emphasis on 3D-bioprinting. A thorough understanding of the uses of 3D-printed dressings in a range of chronic wound scenarios is provided by insights into recent research and patents. EXPERT OPINION: The expert view recognizes wounds as a historical human ailment and emphasizes the growing difficulties and expenses related to wound treatment. The expert acknowledges that 3D printing is revolutionary, but also points out that it is still in its infancy and has the potential to enhance mass production rather than replace it. The review highlights the benefits of 3D printing for wound dressings by providing instances of smart materials that improve treatment results by stimulating angiogenesis, reducing pain, and targeting particular enzymes. The expert advises taking action to convert the technology's prospective advantages into real benefits for patients, even in the face of resistance to change in the healthcare industry. It is believed that the increasing evidence from in-vivo studies is promising and represents a positive change in the treatment of chronic wounds toward sophisticated 3D-printed dressings.

Optimization and Characterization of a Novel Antioxidant Naringenin-Loaded Hydrogel for Encouraging Re-Epithelization in Chronic Diabetic Wounds: A Preclinical Study.

Nonhealed wounds are one of the most dangerous side effects of type-2 diabetes, which is linked to a high frequency of bacterial infections around the globe that eventually results in amputation of limbs. The present investigation aimed to explore the drug-loaded (naringenin) hydrogel system for chronic wound healing. The hydrogel membranes comprising Na-alginate with F-127 and poly(vinyl alcohol) were developed to treat chronic wounds using the quality-by-design (QbD) approach. The optimized formulation was tested for various parameters, such as swelling, gel fraction, water vapor transition rate (WVTR), etc. In vitro evaluation indicated that a drug-loaded hydrogel displayed better tissue adhesiveness and can release drugs for a prolonged duration of 12 h. Scratch assay performed on L929 cell lines demonstrated good cell migration. The diabetic wound healing potential of the hydrogel membrane was assessed in streptozotocin-induced male Wistar rats (50 mg/kg). Higher rates of wound closure, re-epithelialization, and accumulation of collagen were seen in in vivo experiments. Histopathologic investigation correspondingly implied that the drug-loaded hydrogel could enhance dermal wound repair. The improved antimicrobial and antioxidant properties with expedited healing indicated that the drug-loaded hydrogel is a perfect dressing for chronic wounds.

Recent advances in BCRP-induced breast cancer resistance treatment with marine-based natural products.

Breast cancer is the prominent cause of cancer-related death in women globally in terms of incidence and mortality. Despite, recent advances in the management of breast cancer, there are still a lot of cases of resistance to medicines, which is currently one of the biggest problems faced by researchers across the globe. Out of several mechanisms, breast cancer resistance protein (BCRP) arbitrated drug resistance is a major concern. Hormonal, cytotoxic and immunotherapeutic drugs are used in the systemic therapy of breast cancer. It is vital to choose drugs based on the clinical and molecular attributes of the tumor to provide better treatment with greater efficacy and minimal harm. Given the aforementioned necessity, the use of marine flora in treating breast cancer cannot be neglected. The scientists also stressed the value of marine-derived goods in avoiding breast cancer resistance. Future research into the identification of anticancer drugs will heavily draw upon the marine environment's ample supply of marine-derived natural products (MNPs), which have a wide range of biological functions. Cell cycle arrest, induction of apoptosis and anti-angiogenic, anti-proliferative and anti-metastasis actions are all part of their processes. The overview of breast cancer, the mechanisms underlying its resistance, recent clinical trials based on marine-derived products in breast cancer and the use of marine products in the treatment of breast cancer are highlighted in this paper. Moreover, the authors also emphasised the importance of marine-derived products in preventing breast cancer resistance.

New Insights in Topical Drug Delivery for Skin Disorders: From a Nanotechnological Perspective.

Skin, the largest organ in humans, is an efficient route for the delivery of drugs as it circumvents several disadvantages of the oral and parenteral routes. These advantages of skin have fascinated researchers in recent decades. Drug delivery via a topical route includes moving the drug from a topical product to a locally targeted region with dermal circulation throughout the body and deeper tissues. Still, due to the skin's barrier function, delivery through the skin can be difficult. Drug delivery to the skin using conventional formulations with micronized active components, for instance, lotions, gels, ointments, and creams, results in poor penetration. The use of nanoparticulate carriers is one of the promising strategies, as it provides efficient delivery of drugs through the skin and overcomes the disadvantage of traditional formulations. Nanoformulations with smaller particle sizes contribute to improved permeability of therapeutic agents, targeting, stability, and retention, making nanoformulations ideal for drug delivery through a topical route. Achieving sustained release and preserving a localized effect utilizing nanocarriers can result in the effective treatment of numerous infections or skin disorders. This article aims to evaluate and discuss the most recent developments of nanocarriers as therapeutic agent vehicles for skin conditions with patent technology and a market overview that will give future directions for research. As topical drug delivery systems have shown great preclinical results for skin problems, for future research directions, we anticipate including in-depth studies of nanocarrier behavior in various customized treatments to take into account the phenotypic variability of the disease.

Potential of nanoemulsions for accelerated wound healing: innovative strategies.

Wounds represent various significant health concerns for patients and also contribute major costs to healthcare systems. Wound healing comprises of overlapped and various coordinated steps such as homeostasis, inflammation, proliferation, and remodeling. In response to the failure of many strategies in delivering intended results including wound closure, fluid loss control, and exhibiting properties such as durability, targeted delivery, accelerated action, along with histocompatibility, numerous nanotechnological advances have been introduced. To understand the magnitude of wound therapy, this systematic and updated review discussing the effectiveness of nanoemulsions has been undertaken. This review portrays mechanisms associated with wound healing, factors for delayed wound healing, and various technologies utilized to treat wounds effectively. While many strategies are available, nanoemulsions have attracted the tremendous attention of scientists globally for the research in wound therapy due to their long-term thermodynamic stability and bioavailability. Nanoemulsions not only aid in tissue repair, but are also considered as an excellent delivery system for various synthetic and natural actives. Nanotechnology provides several pivotal benefits in wound healing, including improved skin permeation, controlled release, and stimulation of fibroblast cell proliferation. The significant role of nanoemulsions in improved wound healing along with their preparation techniques has also been highlighted with special emphasis on mechanistic insights. This article illustrates recent research advancements for the utilization of nanoemulsions in wound treatment. An adequate literature search has been conducted using the keywords 'Nanoemulsions in wound healing', 'Wound therapy and nanoemulsions', 'Herbal actives in wound therapy', 'Natural oils and wounds treatment' etc., from PubMed, Science Direct, and Google Scholar databases. Referred and original publications in the English language accessed till April 2022 has been included, whereas nonEnglish language papers, unpublished data, and nonoriginal papers were excluded from the study.

Advancement in nanotechnology for treatment of rheumatoid arthritis: scope and potential applications.

Rheumatoid arthritis is a hyperactive immune disorder that results in severe inflammation in synovial joints, cartilage, and bone deterioration, resulting in immobilization of joints. Traditional approaches for the treatment of rheumatoid arthritis are associated with some limiting factors such as suboptimal patient compliance, inability to control the progression of disorder, and safety concerns. Therefore, innovative drug delivery carriers for efficient therapeutic delivery at inflamed synovial sites with better safety assessment are urgently needed to address these issues. From this perspective, nanotechnology is an outstanding alternative to traditional drug delivery approaches, and it has shown great promise in developing novel carriers to treat rheumatoid arthritis. Considering the current research and future application of nanocarriers, it is believed that nanocarriers can be a crucial element in rheumatoid arthritis treatment. This paper covers all currently available pathophysiological aspects of rheumatoid arthritis and treatment options. Future research for the reduction of synovial inflammation should focus on developing multifunction nanoparticles capable of delivering therapeutic agents with improved safety, efficacy, and cost-effectiveness to be commercialized.

Nano-mediated strategy for targeting and treatment of non-small cell lung cancer (NSCLC).

Lung cancer is the most common type of cancer, with over 2.1 million cases diagnosed annually worldwide. It has a high incidence and mortality rate, leading to extensive research into various treatment options, including the use of nanomaterial-based carriers for drug delivery. With regard to cancer treatment, the distinct biological and physico-chemical features of nano-structures have acquired considerable impetus as drug delivery system (DDS) for delivering medication combinations or combining diagnostics and targeted therapy. This review focuses on the use of nanomedicine-based drug delivery systems in the treatment of lung cancer, including the use of lipid, polymer, and carbon-based nanomaterials for traditional therapies such as chemotherapy, radiotherapy, and phototherapy. The review also discusses the potential of stimuli-responsive nanomaterials for drug delivery in lung cancer, and the limitations and opportunities for improving the design of nano-based materials for the treatment of non-small cell lung cancer (NSCLC).

Recent updates on nano-phyto-formulations based therapeutic intervention for cancer treatment.

Cancer is a leading cause of death globally, with limited treatment options and several limitations. Chemotherapeutic agents often result in toxicity which long-term conventional treatment. Phytochemicals are natural constituents that are more effective in treating various diseases with less toxicity than the chemotherapeutic agents providing alternative therapeutic approaches to minimize the resistance. These phytoconstituents act in several ways and deliver optimum effectiveness against cancer. Nevertheless, the effectiveness of phyto-formulations in the management of cancers may be constrained due to challenges related to inadequate solubility, bioavailability, and stability. Nanotechnology presents a promising avenue for transforming current cancer treatment methods through the incorporation of phytochemicals into nanosystems, which possess a range of advantageous characteristics such as biocompatibility, targeted and sustained release capabilities, and enhanced protective effects. This holds significant potential for future advancements in cancer management. Herein, this review aims to provide intensive literature on diverse nanocarriers, highlighting their applications as cargos for phytocompounds in cancer. Moreover, it offers an overview of the current advancements in the respective field, emphasizing the characteristics that contribute to favourable outcomes in both in vitro and in vivo settings. Lastly, clinical development and regulatory concerns are also discussed to check on the transformation of the concept as a promising strategy for combination therapy of phytochemicals and chemotherapeutics that could lead to cancer management in the future.

Recent Advances in Cancer Vaccines: Challenges, Achievements, and Futuristic Prospects.

Cancer is a chronic disease, and it can be lethal due to limited therapeutic options. The conventional treatment options for cancer have numerous challenges, such as a low blood circulation time as well as poor solubility of anticancer drugs. Therapeutic cancer vaccines emerged to try to improve anticancer drugs' efficiency and to deliver them to the target site. Cancer vaccines are considered a viable therapeutic technique for most solid tumors. Vaccines boost antitumor immunity by delivering tumor antigens, nucleic acids, entire cells, and peptides. Cancer vaccines are designed to induce long-term antitumor memory, causing tumor regression, eradicate minimal residual illness, and prevent non-specific or unpleasant effects. These vaccines can assist in the elimination of cancer cells from various organs or organ systems in the body, with minimal risk of tumor recurrence or metastasis. Vaccines and antigens for anticancer therapy are discussed in this review, including current vaccine adjuvants and mechanisms of action for various types of vaccines, such as DNA- or mRNA-based cancer vaccines. Potential applications of these vaccines focusing on their clinical use for better therapeutic efficacy are also discussed along with the latest research available in this field.

Polysaccharide-based hydrogels: New insights and futuristic prospects in wound healing.

Polysaccharides elicit enormous and promising applications due to their extensive obtainability, innocuousness, and biodegradability. Various outstanding features of polysaccharides can be employed to fabricate biomimetic and multifunctional hydrogels as efficient wound dressings. These hydrogels mimic the natural extracellular matrix and also boost the proliferation of cells. Owing to distinctive architectures and abundance of functional groups, polysaccharide-derived hydrogels have exceptional physicochemical properties and unique therapeutic interventions. Hydrogels designed using polysaccharides can effectively safeguard wounds from bacterial attack. This review includes wound physiology and emphasises on numerous polysaccharide-based hydrogels for wound repair applications. Polysaccharide hydrogels for different wound types and diverse therapeutic agents loaded in hydrogels for wound repair with recent patents are portrayed in the current manuscript, debating the potential of fascinating hydrogels for effective wound healing. More research is required to engineer multifaceted advanced polysaccharide hydrogels with tuneable and adjustable properties to attain huge potential in wound healing.

Wound-Healing Effects of Curcumin and Its Nanoformulations: A Comprehensive Review.

Wound healing is an intricate process of tissue repair or remodeling that occurs in response to injury. Plants and plant-derived bioactive constituents are well explored in the treatment of various types of wounds. Curcumin is a natural polyphenolic substance that has been used since ancient times in Ayurveda for its healing properties, as it reduces inflammation and acts on several healing stages. Several research studies for curcumin delivery at the wound site reported the effectiveness of curcumin in eradicating reactive oxygen species and its ability to enhance the deposition of collagen, granulation tissue formation, and finally, expedite wound contraction. Curcumin has been widely investigated for its wound healing potential but its lower solubility and rapid metabolism, in addition to its shorter plasma half-life, have limited its applications in wound healing. As nanotechnology has proven to be an effective technique to accelerate wound healing by stimulating appropriate mobility through various healing phases, curcumin-loaded nanocarriers are used for targeted delivery at the wound sites. This review highlights the potential of curcumin and its nanoformulations, such as liposomes, nanoparticles, and nano-emulsions, etc. in wound healing. This paper emphasizes the numerous biomedical applications of curcumin which collectively prepare a base for its antibiofilm and wound-healing action.

Drug Delivery Strategies and Biomedical Significance of Hydrogels: Translational Considerations.

Hydrogels are a promising and attractive option as polymeric gel networks, which have immensely fascinated researchers across the globe because of their outstanding characteristics such as elevated swellability, the permeability of oxygen at a high rate, good biocompatibility, easy loading, and drug release. Hydrogels have been extensively used for several purposes in the biomedical sector using versatile polymers of synthetic and natural origin. This review focuses on functional polymeric materials for the fabrication of hydrogels, evaluation of different parameters of biocompatibility and stability, and their application as carriers for drugs delivery, tissue engineering and other therapeutic purposes. The outcome of various studies on the use of hydrogels in different segments and how they have been appropriately altered in numerous ways to attain the desired targeted delivery of therapeutic agents is summarized. Patents and clinical trials conducted on hydrogel-based products, along with scale-up translation, are also mentioned in detail. Finally, the potential of the hydrogel in the biomedical sector is discussed, along with its further possibilities for improvement for the development of sophisticated smart hydrogels with pivotal biomedical functions.

PEG mediated destabilization of holo α-lactalbumin probed by in silico and in vitro studies: deviation from excluded volume effect.

Crowded and confined macromolecular milieus surround proteins, and both are stabilizing if the nature of the interaction between crowder and proteins are considered hard-core repulsive interactions. However, non-specific chemical interactions between a protein and its surroundings also play a significant role and the sum effect of both hard-core repulsion and soft interaction balances the overall effect of crowding/confinement. Previous studies showing the effect of polyethylene glycol (PEG) on protein and nucleic acid may be interpreted as either primarily excluded volume effect or, in some cases, chemical effect by changing solvent properties. In case of destabilizing interactions, charge-charge and hydrophobic contact have to gain more attention. For instance, in vitro and in vivo studies using protein as crowding agent revealed the destabilization of proteins induced by charge-charge interactions. To investigate the effect of PEG 10 kDa on holo α-lactalbumin (holo α-LA), structure and thermal stability of the protein were measured at different pH values using several techniques. Structural characterization by Trp-fluorescence, near-UV CD and far-UV measurements at different pH values clearly shows perturbation of tertiary and secondary structure of holo α-LA by PEG 10 kDa. Furthermore, the dynamic light scattering measurement shows that the protein is homogeneous under all experimental conditions. Analysis of the heat-induced denaturation profile in the presence of the crowder shows destabilization of the protein in terms of Tm (midpoint of denaturation) and ΔGD0 (Gibbs free energy change at 25 °C). To evaluate the interaction of PEG 10 kDa with holo α-LA and stability of PEG-α-LA complex, docking and molecular dynamic simulation were carried out for 100 ns.Communicated by Ramaswamy H. Sarma.

Therapeutic Management of COVID-19 Patients: Clinical Manifestation and Limitations.

Coronavirus disease-2019 (COVID-19) is a respiratory tract infection accompanied by severe or fatal pneumonia-like symptoms and sometimes death. It has posed to be an ongoing global health emergency caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to a sudden outbreak and a large number of infections and deaths, it became a major concern all over the world. The options available as effective therapeutics should be urgently exercised to handle this pandemic. So far, no specific and accurate anti- SARS-CoV-2 treatment is recommended because of the absence of sufficient clinical evidence. In such cases, the clinical use of available drugs is always considered to be on top priority. A broad-spectrum antiviral agent, remdesivir, is found effective in many cases and recommended by many clinicians in many countries. This drug acts as a potential inhibitor of viral RNA-dependent RNA polymerase protein and thus likely to be efficacious in SARS-CoV-2 infection. Tocilizumab is currently recommended by many hospitals as an alternative treatment for critically ill COVID-19 patients. Tocilizumab has been administered to control cytokine storms that occur due to the release of proinflammatory cytokine, including interleukin 6. Chloroquine and hydroxychloroquine are also used in hospitals to handle severe COVID-19 patients. Currently, plasma therapy has been exercised as a therapeutic alternative, especially to handle severe COVID-19 patients. In addition, herbal medicines are expected to play a significant role in the control and prevention of COVID-19. All these therapeutic options have their advantages and limitations. This review highlights the therapeutic potential of these available drugs, along with their mechanism of action and shortcomings. We have provided detailed information on available therapeutic options, which have proved to be effective in improving clinical symptoms of severe COVID-19 patients.

Concentration dependent effect of ethylene glycol on the structure and stability of holo α-lactalbumin: Characterization of intermediate state amidst soft interactions.

The interior of the cell is crowded with different kinds of biological molecules with varying sizes, shapes and compositions which may affect physiological processes especially protein folding, protein conformation and protein stability. To understand the consequences of such a crowded environment, pH-induced unfolding of holo alpha-lactalbumin (holo α-LA) was studied in the presence of ethylene glycol (EG). The effect of EG on the folding and stability of holo α-LA in aqueous solution was investigated using several spectroscopic techniques. The results indicate that stabilization/destabilization of holo α-LA by EG is concentration- and pH-dependent. Low concentration of EG stabilizes the protein at pH near its pI. From the results of far-UV CD, UV-visible and ANS fluorescence, intermediate state (MG state) was characterized in the presence of high concentration of ethylene glycol. The results invoke a new mechanism for the formation of MG state identical to active component of BAMLET. MG state of holo α-LA has a direct implication to cancer therapy. MG state of α-LA in complex with specific type of lipid is a novel class of protein-based anti-cancer complexes that incorporate oleic acid and deliver it to the cancer cells.

Molecular basis of pathogenic parasitic infections: insights from parasite kinome.

Infectious diseases caused by numerous parasitic pathogens represent a global health conundrum. Several animal and plant pathogens are responsible for causing acute illness in humans and deadly plant infections. These pathogens have evolved a diverse array of infection strategies and survival methods within the host organism. Recent research has highlighted the role of protein kinases in the overall virulence and pathogenicity of the pathogens. Protein kinases (Pks) are a group of enzymes known to catalyse the phosphorylation of a wide variety of cellular substrates involved in different signalling cascades. They are also involved in regulating pathogen life cycle and infectivity. In this review, we attempt to address the role of parasite kinome in host infection, pathogen survival within the host tissue and thereby disease manifestation. The understanding of the parasite kinome can be a potential target for robust diagnosis and effective therapeutics.

Molecular and macromolecular crowding-induced stabilization of proteins: Effect of dextran and its building block alone and their mixtures on stability and structure of lysozyme.

Dextran 70 and its building block (glucose) has been used as macromolecular crowder and osmolyte, respectively. The difference in size and structure of both made us inquisitive to measure stability of lysozyme in the presence of their mixture. The effects of mixture of a fixed dextran 70 concentration (300 mg/ml) containing different concentrations of glucose and vice versa, were studied. It was observed that Tm (the midpoint of denaturation curve) and △GDo (standard Gibbs free energy change at 25 °C) of lysozyme increase with the increasing concentration of dextran 70 and glucose alone and their mixture. We asked a question whether the effect of synthetic crowding agent on the stability of protein is due to the property of its monomer or due to the crowder. In this study, we observed that both dextran and its monomer stabilize the protein by same mechanism which is volume exclusion. The stabilization arises due to change in in the entropy of unfolding, while there is insignificant change in enthalpy of the protein with increasing concentration of the co-solute. Furthermore, the efficacy of stabilization by glucose increases in the crowded environment, when the concentration of dextran 70 is more than 200 mg/ml in the mixture.

Brain targeted oral delivery of doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles against ketamine induced psychosis: behavioral, biochemical, neurochemical and histological alterations in mice.

To develop statistically optimized brain targeted Tween 80 coated chitosan nanoparticulate formulation for oral delivery of doxycycline hydrochloride for the treatment of psychosis and to evaluate its protective effect on ketamine induced behavioral, biochemical, neurochemical and histological alterations in mice. 32 full factorial design was used to optimize the nanoparticulate formulation to minimize particle size and maximize entrapment efficiency, while independent variables chosen were concentration of chitosan and Tween 80. The optimized formulation was characterized by particle size, drug entrapment efficiency, Fourier transform infrared, Transmission electron microscopy analysis and drug release behavior. Pure doxycycline hydrochloride (25 and 50 mg/kg, p.o.) and optimized doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles (DCNPopt) (equivalent to 25 mg/kg doxycycline hydrochloride, p.o.) were explored against ketamine induced psychosis in mice. The experimental studies for DCNPopt, with mean particle size 237 nm and entrapment efficiency 78.16%, elucidated that the formulation successfully passed through blood brain barrier and exhibited significant antipsychotic activity. The underlying mechanism of action was further confirmed by behavioral, biochemical, neurochemical estimations and histopathological study. Significantly enhanced GABA and GSH level and diminished MDA, TNF-α and dopamine levels were observed after administration of DCNPopt at just half the dose of pure doxycycline hydrochloride, showing better penetration of doxycyline hydrochloride in the form of Tween 80 coated nanoparticles through blood brain barrier. This study demonstrates the hydrophilic drug doxycycline hydrochloride, loaded in Tween 80 coated chitosan nanoparticles, can be effectively brain targeted through oral delivery and therefore represents a suitable approach for the treatment of psychotic symptoms.