Development and biological evaluation of smart powder bandage for wound healing and dressing applications.

Cutaneous wounds are one of the pressing concerns for healthcare systems globally. With large amounts of water, conventional hydrogels encounter obstacles in effectively delivering small molecules and peptides for wound healing. The surplus water content challenges the stability and sustained release of small molecules and peptides, diminishing their therapeutic efficacy. Our pioneering smart powder bandage, fabricated through freeze-drying, ensures a water content of <1 % during storage. Upon contact with wound exudate, it forms hydrogel layers, thereby optimizing the delivery of peptides. Tailored for thermosensitive peptides such as EGF, this strategy surmounts the limitations of conventional hydrogels, providing a robust platform for efficacious therapeutic delivery in wound healing applications. Developing multifunctional wound dressings with antibacterial, anti-inflammatory, hemostatic, and healing properties is essential to promote wound healing. Therefore, the current investigation reports the development of multifunctional EGF@Silnanom SPB with the above-mentioned properties to promote wound healing using silver nanomix (Silnanom) and bioactive epidermal growth factors (EGF) as active therapeutics. The characterization of smart powder bandage (SPB) revealed that Silnanom were homogeneously dispersed in the entangled polymer network. The multifunctional smart powder bandage exhibited high bacterial inhibition rates against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and rigorous hemocompatibility, cell compatibility, and in vivo studies also confirmed its biocompatibility. Furthermore, multifunctional EGF@Silnanom SPB effectively reduced pro-inflammatory markers, enhanced collagen deposition, promoted angiogenesis, and accelerated wound healing in a full-thickness mouse wound model through the sustained release of Silnanom and EGF. Additionally, the results of hemostasis analysis on the tail amputation mouse model confirmed the hemostasis properties of the EGF@Silnanom SPB. Overall, the multifunctional EGF@Silnanom SPB shows promising potential for skin wound repair, offering a potent and effective solution to the challenges posed by conventional wound dressings.

Carbonaceous Nanomaterials for Phototherapy of Cancer.

Carbonaceous nanomaterials (CNMs) have drawn tremendous biomedical research interest because of their unique structural features. Recently, CNMs, namely carbon dots, fullerenes, graphene, etc, have been successful in establishing them as considerable nanotherapeutics for phototherapy applications due to their electrical, thermal, and surface properties. This review aims to crosstalk the current understanding of CNMs as multimodal compounds in photothermal and photodynamic therapies as an integrated approach to treating cancer. It also expounds on phototherapy's biomechanics and illustrates its relation to cancer biomodulation. Critical considerations related to the structural properties, fabrication approaches, surface functionalization strategies, and biosafety profiles of CNMs have been explained. This article provides an overview of the most recent developments in the study of CNMs used in phototherapy, emphasizing their usage as nanocarriers. To conquer the current challenges of CNMs, we can raise the standard of cancer therapy for patients. The review will be of interest to the researchers working in the area of photothermal and photodynamic therapies and aiming to explore CNMs and their conjugates in cancer therapy.

Development and Evaluation of Silver Nanomix as a Next-Generation Tool for Wound Healing and Dressing Applications.

This investigation reports silver nanomix as a next-generation, cost-effective, and clinically translatable nanomaterial tool for wound healing and dressing applications. Silver nanomix was developed by systematically hybridizing silver nanoparticles (AgNPs; sub-15 nm; Design Expert tool) with ionic Ag. The silver nanomix elicited significantly higher antibacterial potential than conventional silver products and marketed reference antibiotics, as studied in Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Furthermore, the biomechanics of action, safety profile, and intracellular silver organization by silver nanomix are also studied exhaustively. This research presents a viewpoint and direction in designing silver-based antimicrobial dressings with a 40% reduction in their cost.

A Bird's Eye View of Various Cell-Based Biomimetic Nanomedicines for the Treatment of Arthritis.

Arthritis is the inflammation and tenderness of the joints because of some metabolic, infectious, or constitutional reasons. Existing arthritis treatments help in controlling the arthritic flares, but more advancement is required to cure arthritis meticulously. Biomimetic nanomedicine represents an exceptional biocompatible treatment to cure arthritis by minimizing the toxic effect and eliminating the boundaries of current therapeutics. Various intracellular and extracellular pathways can be targeted by mimicking the surface, shape, or movement of the biological system to form a bioinspired or biomimetic drug delivery system. Different cell-membrane-coated biomimetic systems, and extracellular-vesicle-based and platelets-based biomimetic systems represent an emerging and efficient class of therapeutics to treat arthritis. The cell membrane from various cells such as RBC, platelets, macrophage cells, and NK cells is isolated and utilized to mimic the biological environment. Extracellular vesicles isolated from arthritis patients can be used as diagnostic tools, and plasma or MSCs-derived extracellular vesicles can be used as a therapeutic target for arthritis. Biomimetic systems guide the nanomedicines to the targeted site by hiding them from the surveillance of the immune system. Nanomedicines can be functionalized using targeted ligand and stimuli-responsive systems to reinforce their efficacy and minimize off-target effects. This review expounds on various biomimetic systems and their functionalization for the therapeutic targets of arthritis treatment, and discusses the challenges for the clinical translation of the biomimetic system.

Recent Advances in Polymer-Based Nanomaterials for Non-Invasive Photothermal Therapy of Arthritis.

To date, nanomaterials have been widely used for the treatment and diagnosis of rheumatoid arthritis. Amongst various nanomaterials, polymer-based nanomaterials are becoming increasingly popular in nanomedicine due to their functionalised fabrication and easy synthesis, making them biocompatible, cost-effective, biodegradable, and efficient nanocarriers for the delivery of drugs to a specific target cell. They act as photothermal reagents with high absorption in the near-infrared region that can transform near-infrared light into localised heat with fewer side effects, provide easier integration with existing therapies, and offer increased effectiveness. They have been combined with photothermal therapy to understand the chemical and physical activities behind the stimuli-responsiveness of polymer nanomaterials. In this review article, we provide detailed information regarding the recent advances in polymer nanomaterials for the non-invasive photothermal treatment of arthritis. The synergistic effect of polymer nanomaterials and photothermal therapy has enhanced the treatment and diagnosis of arthritis and reduced the side effects of drugs in the joint cavity. In addition, further novel challenges and future perspectives must be resolved to advance polymer nanomaterials for the photothermal therapy of arthritis.

A 3D-Printed Graphene BioFuse Implant for Postsurgical Adjuvant Therapy of Cancer: Proof of Concept in 2D- and 3D-Spheroid Tumor Models.

Three-dimensional printing is an emerging technology that is finding its niche applications in diverse fields owing to its flexibility concerning personalization and design. Surgery followed by adjuvant therapy is the standard treatment plan in most cancers from stage I to stage III. Most of the available adjuvant therapies, like chemotherapy, radiation therapy, immunotherapy, hormonal therapy, etc., are associated with severe side effects that considerably reduce the quality of life of patients. In addition, there is always the chance of tumor recurrence or metastasis development followed by surgery. This investigation reports the development of a 3D-printed, biodegradable, laser-responsive implant with a chemo-combined thermal ablating potential for adjuvant therapy of cancer. The 3D-printable ink was developed using poly(l-lactide) and hydroxypropyl methylcellulose as the base polymer, doxorubicin as the chemotherapeutic agent, and reduced graphene oxide as the photothermal ablating agent. The personalized implant released the drug pH-dependently (p value < 0.0001) for an extended period (93.55 ± 1.80% → 28 days). The 3D-printed implant exhibited acceptable biophysical properties (tensile strength: 3.85 ± 0.15 MPa; modulus: 92.37 ± 11.50 MPa; thickness: 110 µm) with laser-responsive hyperthermia (ΔT: 37 ± 0.9 °C → 48.5 ± 1.07 °C; 5 min; 1.5 W/cm2) and inherent biodegradable property (SEM analysis). The 3D-printed implant was evaluated for its therapeutic potential in 2D- and 3D-spheroid tumor models (MDA-MB 231 and SCC 084 2D cells) employing MTT cytotoxicity assay, apoptosis assay, cell cycle analysis, and gene expression analysis. The biomolecular aspects and biomechanics of the 3D-printed BioFuse implant were also evaluated by determining the effect of treatment on the expression levels of HSP1A, Hsp70, BAX, and PTEN. It is advocated that the knowledge developed in this project will significantly assist and advance the science aiming to develop a clinically translatable postsurgical adjuvant therapy for cancer.

Lung-on-chip microdevices to foster pulmonary drug discovery.

Respiratory diseases account for unprecedented mortality owing to a lack of personalized or insufficient therapeutic interventions. Fostering pulmonary research into managing pulmonary threat requires a potential alternative approach that can mimick the in vivo complexities of the human body. The in vitro miniaturized bionic simulation of the lung holds great potential in the quest for a successful therapeutic intervention. This review discusses the emerging roles of lung-on-chip microfluidic simulator devices in fostering translational pulmonary drug discovery and personalized medicine. This review also explicates how the lung-on-chip model emulates the breathing patterns, elasticity, and vascularization of lungs in creating a 3D pulmonary microenvironment.

Cancer Cell-Specific and Laser-Activatable NanoSeeds for Targeted Photothermal Ablation of Triple-Negative Breast Cancer.

This investigation reports the quality-by-design (QbD) assisted novel templated approach for developing cancer cell-specific and laser-activatable nanoseeds (AuraTherm) for targeted photothermal ablation of triple-negative breast cancer (TNBC). AuraTherm was nanometric in size as characterized by SEM, TEM and particle analysis (80.28 ± 2.56 nm; -21.80 ± 0.17 mV) with hemocompatibility and neutrality towards blood components. AuraTherm showed reversible photothermal effect (ΔT: 37 ± 1.2°C → 49.4 ± 1.5°C; 15 min; 2.4 W cm-2 ) employing near-infrared 808 nm laser (NIR-808). The targeted cytosolic localization led to a significant anticancer activity as evaluated using apoptosis assay, cell cycle analysis, Intracellular ROS generation assay, cellular uptake and receptor binding assay. The NIR-808 laser-responsive photothermal ablation of cancer cell was found to be more effective compared to without NIR-808 laser-treated counterparts, suggesting the fundamental role of photothermal ablation in the treatment of TNBC.

Innovation in Strategies for Sensitivity Improvement of Chromatography and Mass Spectrometry Based Analytical Techniques.

Chromatography and mass spectrometry based techniques are the most commonly employed procedures to quantitate the analytes in pharmaceutical research. However, sensitivity of analytical methods significantly varies due to the difference in physicochemical characteristics of analytes. Sensitivity of methods greatly affects the quality of analytical results. Establishment of a sufficiently sensitive method ensures the suitability of a technique for its intended purpose. Although various types of advancement in chromatographic science are witnessed, issues related to sensitivity remain a major challenge for the analyte with low detection limit. Highly sensitive analytical methods are specifically essential to quantitate the analytes in the samples from dissolution study of sustained release formulations, cross-contamination study, impurity analysis, metabolite profiling, bioanalysis of highly potent and low bioavailable drugs. In recent years, huge involvement of researchers toward sensitivity enhancement of quantitative methods is evidenced. Wide verities of approaches are being reported in the field. Derivatization technique, introduction of ion-pairing reagents, sample pretreatment, and utilization of innovative methods such as 2-dimensional liquid chromatography, nano liquid chromatography, 2-dimensional gas chromatography, supercritical fluid chromatography, use of microcolumn are some approaches that are being employed. Online sample preparation techniques can significantly improve the sensitivity of a method by reducing sample loss and degradation. This review summarizes and critically discussed the approaches to improve the sensitivity of chromatographic and mass spectrometry based analytical methods. This article can guide the researchers to select suitable approaches for achieving the desired detection limit of analytical and bioanalytical methods based on their specific requirements.

Nanoplatform-Integrated Miniaturized Solid-Phase Extraction Techniques: A Critical Review.

Preparation of the biological samples is one of the most critical steps in sample analysis. In past decades, the liquid-liquid extraction technique has been used to extract the desired analytes from complex biological matrices. However, solid-phase extraction (SPE) gained popularity due to versatility, simplicity, selectivity, reproducibility, high sample recovery %, solvent economy, and time-saving nature. The superior extraction efficiency of SPE can be attributed to the development of advanced techniques, including the nanosorbents technology. The nanosorbent technology significantly simplified the sample preparation, improved the selectivity, diversified the application, and accelerated the sample analysis. This review critically expands on the to-date advancements reported in SPE with particular regards to the nanosorbent technology.

Current Update on Transcellular Brain Drug Delivery.

It is well known that the presence of a blood-brain barrier (BBB) makes drug delivery to the brain more challenging. There are various mechanistic routes through which therapeutic molecules travel and deliver the drug across the BBB. Among all the routes, the transcellular route is widely explored to deliver therapeutics. Advances in nanotechnology have encouraged scientists to develop novel formulations for brain drug delivery. In this article, we have broadly discussed the BBB as a limitation for brain drug delivery and ways to solve it using novel techniques such as nanomedicine, nose-to-brain drug delivery, and peptide as a drug delivery carrier. In addition, the article will help to understand the different factors governing the permeability of the BBB, as well as various formulation-related factors and the body clearance of the drug delivered into the brain.

CD44-Receptor Targeted Gold-Doxorubicin Nanocomposite for Pulsatile Chemo-Photothermal Therapy of Triple-Negative Breast Cancer Cells.

This study reports the CD44 receptor-targeted gold-doxorubicin nanocomposite (TGNC-DOX) for pulsatile chemo-photothermal therapy of triple-negative breast cancer (TNBC). The developed TGNC-DOX was nanometric, having a particle size of 71.34 ± 3.66 nm. The doxorubicin was loaded by electrostatic interaction with high entrapment and loading efficiency (>75%). TGNC-DOX showed potent photothermal response and reversible photothermal stability following irradiation with 808 nm NIR laser irradiation. Further, TGNC-DOX showed laser-responsive and pH-dependent drug release behavior suggesting its suitability for chemo-photothermal therapy, specifically at the tumor microenvironment site. Cellular viability, cellular uptake, ROS generation, and apoptosis assays suggested selective localization of TGNC-DOX in cancer cells that showed a significant cytotoxic effect against MDA-MB-231 breast cancer cells. Moreover, the developed TGNC-DOX showed ferroptosis in MDA-MB-231 cells. The event of TGNC-DOX-mediated thermal ablation is marked by a significant generation of reactive oxygen species (ROS) and apoptosis, as affirmed by flow cytometry. NIR-808 laser-responsive photothermal therapy of cancer cells was found to be more effective than without NIR-808 laser-treated cells, suggesting the fundamental role of photothermal ablation. The outcome concludes developed TGNC-DOX is a novel and potential tool to mediate laser-guided chemo-photothermal ablation treatment of cancer cells.

Emerging ROS-Modulating Technologies for Augmentation of the Wound Healing Process.

Reactive oxygen species (ROS) is considered a double-edged sword. The slightly elevated level of ROS helps in wound healing by inhibiting microbial infection. In contrast, excessive ROS levels in the wound site show deleterious effects on wound healing by extending the inflammation phase. Understanding the ROS-mediated molecular and biomolecular mechanisms and their effect on cellular homeostasis and inflammation thus substantially improves the possibility of exogenously augmenting and manipulating wound healing with the emerging antioxidant therapeutics. This review comprehensively delves into the relationship between ROS and critical phases of wound healing and the processes underpinning antioxidant therapies. The manuscript also discusses cutting-edge antioxidant therapeutics that act via ROS scavenging to enhance chronic wound healing.

'Transfersome-embedded-gel' for dual-mechanistic delivery of anti-psoriatic drugs to dermal lymphocytes.

AIM: Develop a platform for co-delivering clobetasol propionate (CP) and cyclosporine (CyA) to the epidermis and dermis to treat psoriasis. METHODS: The transfersomes were prepared by thin-film hydration method. Transfersomes were characterised by dynamic light scattering and transmission electron microscope (TEM). Then, the gel stability, viscosity, pH, and spreadability were measured. Cytotoxicity of the CyA-loaded transfersome embedded in CP-dispersed gel (TEG-CyA-CP) was assessed on both human keratinocyte cell line (HaCaT) and Jurkat cells. In vitro cellular uptake and ex vivo dermal distribution was measured. The expression of inflammatory markers was assessed by reverse-transcription PCR (RT-PCR). RESULTS: Nanoscale (<150 nm) transferosomes with high CyA encapsulation efficiency (>86%) were made. TEG-CyA-CP demonstrated higher viscosity (4808.8 ± 12.01 mPas), which may help control dual drug release. Ex vivo results showed TEG-CyA-CP ability to deliver CyA in the dermis and CP in the epidermis. RT-PCR studies showed the optimised formulation helps reduce the tumour necrosis factor (TNF-α) and interleukin-1 (IL-1) levels to relieve psoriasis symptoms. CONCLUSION: The developed TEG-CyA-CP represents a promising fit-to-purpose delivery platform for the dual-site co-delivery of CyA and CP in treating psoriasis.

Laser activatable nanographene colloids for chemo-photothermal combined gene therapy of triple-negative breast cancer.

This investigation reports the green approach for developing laser activatable nanoscale-graphene colloids (nGC-CO-FA) for chemo-photothermal combined gene therapy of triple-negative breast cancer (TNBC). The nano colloid was found to be nanometric as characterized by SEM, AFM, and zeta sizer (68.2 ± 2.1 nm; 13.8 ± 1.2 mV). The doxorubicin (Dox) loaded employing hydrophobic interaction/π-π stacking showed >80% entrapment efficiency with a sustained pH-dependent drug release profile. It can efficiently incorporate siRNA and Dox and successfully co-localize them inside TNBC cells to obtain significant anticancer activity as evaluated using CCK-8 assay, apoptosis assay, cell cycle analysis, cellular uptake, fluorescence assay, endosomal escape study, DNA content analysis, and gene silencing efficacy studies. nGC-CO-FA/Dox/siRNA released the Dox in temperature- and a pH-responsive manner following NIR-808 laser irradiation. The synergistic photo-chemo-gene therapy using near infrared-808 nm laser (NIR-808) irradiation was found to be more effective as compared to without NIR-808 laser-treated counterparts (∆T: 37 ± 1.1 °C → to 49.2 ± 3.1 °C; 10 min; 0.5 W/cm2), suggesting the pivotal role of photothermal combined gene-therapy in the treatment of TNBC.

Engineering immunity via skin-directed drug delivery devices.

Extensive research is underway to discover a safe and effective vehicle to deliver the vaccines at the desired cutaneous site. These efforts majorly comprise the development of a fit-to-purpose vehicle for in-situ intracutaneous vaccine delivery for achieving the systemic cellular and humoral response to combat infectious diseases. Advancements in nanoscience, bioengineering, and skin science provided much support to vaccine adjuvant development. However, the bench-to-bed side translation of vaccines is still unsatisfactory. A skilfully designed vaccine delivery program aiming to translate the product into market use must address safety, efficacy, scaleup, reproducibility, cost of production, self-administrative potential, and regulatory concerns. This review provides deep insights into skin immunization approaches like mucosal vaccines, cellular/molecular immunological responses, and antigen-adjuvant combinations in modulating immunity. Further, the manuscript discusses distinct vaccine delivery systems used to date for engineering skin immunization, including microparticles, nanoparticles, spherical nucleic acids, STAR particles, niosomes, dendrimers, ethosomes, liposomes, and microneedles. The manuscript will interest researchers working towards developing a next-generation fit-to-purpose vehicle for intracutaneous vaccine delivery.

Recent advancements and future submissions of silica core-shell nanoparticles.

The core-shell silica-based nanoparticles (CSNPs) possess outstanding properties for developing next-generation therapeutics. CSNPs provide greater surface area owing to their mesoporous structure, which offers a high opportunity for surface modification. This review highlights the potential of core-shell silica-based nanoparticle (CSNP) based injectable nanotherapeutics (INT); its role in drug delivery, biomedical imaging, light-triggered phototherapy, Plasmonic enhancers, gene delivery, magnetic hyperthermia, immunotherapy, and potential as next-generation theragnostic. Specifically, the conceptual crosstalk on modern synthetic strategies, biodistribution profiles with a mechanistic view on the therapeutics loading and release modeling are dealt in detail. The manuscript also converses the challenges associated with CSNPs, regulatory hurdles, and their current market position.

Integrated nanomaterials for non-invasive photothermal therapy of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that causes swelling, redness, and arthralgia of multiple joints. Despite significant research and development on the treatment modalities for RA, there is still no established effective treatment option for eradicating joint damage and inflammation. In recent years, photothermal therapy (PTT) has emerged as a practical approach to treat RA. In this review, we outline various factors that affect the effective treatment of RA. Moreover, we discuss various PTT-based nanomaterials that can be used to treat RA.

Innovation in bioanalytical strategies and in vitro drug-drug interaction study approaches in drug discovery.

Failure to evaluate actual toxicities of investigational molecules in drug discovery is majorly due to inadequate evaluation of their pharmacokinetics. Limitation of conventional drug metabolism profiling procedure demands advancement of existing approaches. Various techniques such as 3D cell culture system, bio microfluidic OoC model, sandwich culture model is in pipeline to be employed at their full potential in drug discovery phase. Although they outweigh the conventional techniques in various aspects, a more detailed exploration of applicability in terms of automation and high throughput analysis is required. This review extensively discusses various ongoing innovations in bioanalytical techniques. The review also proposed various scientific strategies to be adopted for prior assessment of interaction possibilities in translational drug discovery research.

Current Scenario and Future Prospect in the Management of COVID-19.

The COVID-19 pandemic continues to wreak havoc worldwide due to the lack of risk assessment, rapid spreading ability, and propensity to precipitate severe disease in comorbid conditions. In an attempt to fulfill the demand for prophylactic and treatment measures to intercept the ongoing outbreak, the drug development process is facing several obstacles and renaissance in clinical trials, including vaccines, antivirals, immunomodulators, plasma therapy, and traditional medicines. This review outlines the overview of SARS-CoV-2 infection, significant recent findings, and ongoing clinical trials concerning current and future therapeutic interventions for the management of advancing pandemic of the century.