'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.

Role of Omega-3 Fatty Acids and Butter Oil in Targeting Delivery of Donepezil Hydrochloride Microemulsion to Brain via the Intranasal Route: a Comparative Study.

In order to investigate the possible role of butter oil (BO) and omega-3 fatty acids-rich fish oil (O3FO) in the delivery of donepezil hydrochloride microemulsion (DH-ME) to the brain via intranasal route, the present study was conducted. DH:BO and DH:O3FO binary mixtures (9:1 to 1:9) were prepared by simple physical mixing and subjected to in vitro diffusion study. Ratios of DH:BO and DH:O3FO, which showed the highest diffusion, were selected for further development of microemulsion (ME). Globule sizes of DH-BO-ME and DH-O3FO-ME were found to be 87.66 ± 5.23 nm and 88.59 ± 8.23 nm, respectively. Nasal histopathological study and in vitro cytotoxicity study revealed the safety of the formulation. Higher percentage of nasal diffusion was found with DH-BO-ME (71.22 ± 1.21%) and DH-O3FO-ME (62.16 ± 1.23%) in comparison to DH-ME (59.69 ± 1.74%) and DH solution (55.01 ± 1.19%), which was further supported by in vitro cell permeability study. After intranasal administration, %bioavailability of drug in the rat brain (Sprague-Dawley rats)(on the basis of DH-ME IV) was higher with DH-BO-ME (313.59 ± 12.98%) and DH-O3FO-ME (361.73 ± 15.15%) in comparison to DH-ME (168.62 ± 6.60%) and DH solution (8.960 ± 0.23%). The results of ex vivo diffusion study and in vivo pharmacokinetic study suggested that BO and O3FO helped in enhancing the nasal permeability and the brain uptake of drug when administered intranasally.

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.

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.

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.

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.

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.

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.

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.

Reinforced electrospun nanofiber composites for drug delivery applications.

Electrospun technology becomes a valuable means of fabricating functional polymeric nanofibers with distinctive morphological properties for drug delivery applications. Nanofibers are prepared from the polymer solution, which allows the direct incorporation of therapeutics such as small drug molecules, genes, and proteins by merely mixing them into the polymeric solution. Due to their biocompatibility, adhesiveness, sterility, and efficiency in delivering diverse cargoes, electrospun nanofibers have gained much attention. This review discusses the capabilities of the electrospun nanofibers in delivering different therapeutics like small molecules, genes, and proteins to their desired target site for treating various ailments. The potential of nanofibers in administering through multiple administration routes and the associated challenges has also been expounded along with a cross-talk about the commercial products of nanofibers for biomedical applications.

Biosimilars accessible in the market for the treatment of cancer.

Biosimilars are the biological product clinically identical to a biologic reference standard regarding their strength, purity, and safety. A large segment of biosimilars has been developed for the treatment of cancer. This review aims to discuss various facets of biosimilars and explicates on biosimilars accessible in the market for cancer clinical intervention. It also illustrates the outcomes of recent clinical trial studies concerning biosimilars. Further, it also crosstalk the safety profiles, regulatory approval requirements, and allied challenges therein. The work will be of significant interest to researchers working in the field of biologics and biosimilars.

Exosomes in multidrug-resistant cancer.

Multiple drug resistance (MDR) is a significant challenge in the treatment of cancer using chemotherapy. There are numerous reasons and mechanisms that are responsible for the development of MDR in cancer tissues. Further, exosomes and its constituents also play a vital role in limiting the efficacy of chemotherapeutic agents. Exosomes are well known for their role in developing resistance in addition to promoting tumor advancement and metastasis. This review discusses the role of exosomes in the development of drug resistance along with their allied mechanisms. This review also discusses the upregulation and downregulation of various exosomal components, which can be effectively employed as diagnostic biomarkers in the treatment of cancer. The essential applications of exosomes to treat drug-resistant cancer have also been discussed.