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Despite the availability of a number of efficacious treatments for Parkinson's disease, their limitations and drawbacks, particularly related to low brain bioavailability and associated side effects, emphasize the need for alternative and more effective therapeutic approaches. Nanomedicine, the application of nanotechnology in medicine, has received considerable interest in recent years as a method of effectively delivering potentially therapeutic molecules to the brain. In particular, polymeric nanoparticles, constructed from biodegradable polymer, have shown great promise in enhancing therapeutic efficacy, reducing toxicity, and ensuring targeted delivery. However, their clinical translation remains a considerable challenge. This article reviews recent in vitro and in vivo studies using polymeric nanoparticles as drug and gene delivery systems for Parkinson's disease with their challenges and future directions. We are also particularly interested in the technical properties, mechanism, drugs release patterns, and delivery strategies to overcome the blood–brain barrier. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Bone-related disorders create critical-sized bone defects that require multifunctional bone graft materials for successful bone repair. Integration of therapeutics with 3D-printed calcium phosphate (CaP) scaffolds offers a personalized treatment option. The inherent properties of CaP enable it to act as a bone substitute, while drug delivering abilities provide a new dimension through localized drug delivery. It enhances both therapeutic efficacy and patient compliance. Controlled delivery of drugs significantly impacts the process of bone regeneration. It can be achieved through various strategies, including polymer coatings, formulation integration, microporous scaffold design, chemical crosslinking, and direct extrusion 3D printing. Understanding drug release mechanisms aids in assessing the in vivo performance of multifunctional scaffolds. 3D printing has revolutionized bone tissue engineering (BTE) by enabling the fabrication of patient- or defect-specific scaffolds to enhance bone regeneration. The superior biocompatibility, customizable bioactivity, and biodegradability have enabled calcium phosphate (CaP) to gain significance as a bone graft material. 3D-printed (3DP) CaP scaffolds allow precise drug delivery due to their porous structure, adaptable structure–property relationship, dynamic chemistry, and controlled dissolution. The effectiveness of conventional scaffold-based drug delivery is hampered by initial burst release and drug loss. This review summarizes different multifunctional drug delivery approaches explored in controlling drug release, including polymer coatings, formulation integration, microporous scaffold design, chemical crosslinking, and direct extrusion printing for BTE applications. The review also outlines perspectives and future challenges in drug delivery research, paving the way for next-generation bone repair methodologies. [ABSTRACT FROM AUTHOR]

Conventional chemotherapeutic agents are limited by their lack of targeting and penetration and their short retention time, and chemotherapy might induce an immune suppressive environment. Peptide self‐assembly can result in a specific morphology, and the resulting morphological changes are stimuli responsive to the external environment, which is important for drug permeation and retention of encapsulated chemotherapeutic agents. In this study, a polypeptide (Pep1) containing the peptide sequences PLGLAG and RGD that is responsive to matrix metalloproteinase 2 (MMP‐2) was successfully developed. Pep1 underwent a morphological transformation from a spherical structure to aggregates with a high aspect ratio in response to MMP‐2 induction. This drug delivery system (DI/Pep1) can transport doxorubicin (DOX) and indomethacin (IND) simultaneously to target tumor cells for subsequent drug release while extending drug retention within tumor cells, which increases immunogenic cell death and facilitates the immunotherapeutic effect of CD4+ T cells. Ultimately, DI/Pep1 attenuated tumor‐associated inflammation, enhanced the body's immune response, and inhibited breast cancer growth by combining the actions of DOX and IND. Our research offers an approach to hopefully enhance the effectiveness of cancer treatment. [ABSTRACT FROM AUTHOR]

Hydrogels have been used in the clinic since the late 1980s with broad applications in drug delivery, cosmetics, tissue regeneration, among many other areas. The past three decades have witnessed rapid advances in the fields of polymer chemistry, crosslinking approaches, and hydrogel fabrication methods, which have collectively brought many new hydrogel products, either injectable or non‐injectable, to clinical studies. In an article published in 2020 entitled "Hydrogels in the clinic", we reviewed the clinical landscape and translational challenges of injectable hydrogels. Here, we provide an update on the advances in the field and also extend the scope to include non‐injectable hydrogels. We highlight recently approved hydrogel products, provide an update on the clinical trials of injectable hydrogels, and discuss active clinical trials of topically applied and implantable hydrogels. [ABSTRACT FROM AUTHOR]

Antibody‐drug conjugates (ADCs), chemotherapeutic agents conjugated to an antibody to enhance their targeted delivery to tumors, represent a significant advancement in cancer therapy. ADCs combine the precise targeting capabilities of antibodies and the potent cell‐killing effects of chemotherapy, allowing for enhanced cytotoxicity to tumors while minimizing damage to healthy tissues. Here, we provide an overview of the current clinical landscape of ADCs, highlighting 11 U.S. Food and Drug Administration (FDA)‐approved products and discussing over 500 active clinical trials investigating newer ADCs. We also discuss some key challenges associated with the clinical translation of ADCs and highlight emerging strategies to overcome these hurdles. Our discussions will provide useful guidelines for the future development of safer and more effective ADCs for a broader range of indications. [ABSTRACT FROM AUTHOR]

Silica nanoparticles (SNPs) have been extensively studied and used in different dental applications to promote improved physicochemical properties, high substance loading efficiency, in addition to sustained delivery of substances for therapeutic or preventive purposes. Therefore, this study aimed to review the SNPs applications in nanomaterials and nanoformulations in dentistry, discussing their effect on physicochemical properties, biocompatibility and ability to nanocarry bioactive substances. Literature searches were conducted on PubMed, Web of Science, and Scopus databases to identify studies examining the physicochemical and biological properties of dental materials and formulations containing SNPs. Data extraction was performed by one reviewer and verified by another A total of 50 were reviewed. In vitro studies reveal that SNPs improved the general properties of dental materials and formulations, such as microhardness, fracture toughness, flexural strength, elastic modulus and surface roughness, in addition to acting as efficient nanocarriers of substances, such as antimicrobial, osteogenic and remineralizing substances, and showed biocompatibility SNPs are biocompatible, improve properties of dental materials and serve as effective carriers for bioactive substances Overall, SNPs are a promising drug delivery system that can improve dental materials biological and physicochemical and aesthetic properties, increasing their longevity and clinical performance. However, more studies are needed to elucidate SNPs short- and long-term effects in the oral cavity, mainly on in vivo and clinical studies, to prove their effectiveness and safety. • Silica nanoparticles have been widely studied and used in dentistry in intra and extraoral materials and formulations. • In vitro results reveal that silica nanoparticles enhance the physicochemical properties of dental materials. • In vitro results also confirm the potential silica nanoparticles can effectively load and release antimicrobial substances, acting as a sustained-release drug delivery system. [ABSTRACT FROM AUTHOR]

Acyclovir (ACY) is used to treat oral viral herpes but has low solubility and bioavailability. Stearic acid (SA) is lipophilic and can be combined with drugs. Therefore, this study aimed to characterize the properties of SA nanoparticles in increasing the cellular uptake of ACY by oral epithelial cells. The hypothesis was that SA nanoparticles increase sustained ACY release, are stable, and increase drug uptake. The production parameters (duration and amplitude of sonication) were optimized to produce solid lipid nanoparticles (SLN) of SA-containing ACY. Particle stability was characterized under different storage conditions (4 °C and 37 °C for 1, 15, and 45 days). SLN were further characterized for their pharmacokinetic profile, cytotoxicity, in vitro permeability, and ability to modulate gene expression and promote ACY uptake by oral epithelial cells. Pharmacokinetic studies revealed sustained and diffusional release of ACY from the SLN, with an initial burst release of 15 min. After 45 d of storage, SLN kept at both 4 °C and 37 °C showed a maximum release of > 90 % of the drug at 120 min. Cells treated with SLN presented a significantly higher intracellular drug content than those treated with ACY and significantly increased the genetic expression of TJP-1 , OCLN , and ECAD. The hypothesis was accepted as SA nanoparticles containing ACY can sustain drug delivery and enhance its absorption into epithelial cells. Therefore, SA nanoparticles are promising for improving ACY uptake in treating oral herpes and other infections caused by HSV-1. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer type and second leading cause of cancer‐related deaths worldwide, requiring novel drug‐delivery concepts. ITC@ZrO(TocP)/ZrO(FdUMP) core@shell nanocarriers (designated ITC‐FdUMP‐NC) with the clinically relevant chemotherapeutics irinotecan (ITC) and fluoro‐2′‐deoxyuridine‐5′‐phosphate (FdUMP) (active derivative of 5′‐fluorouracil/5‐FU) are a new type of nanocarrier with high drug payload (22 wt% of lipophilic ITC: particle core; 10 wt% of hydrophilic FdUMP: particle shell). The nanocarriers are tested in different CRC cell lines, a normal cell line, and rectal cancer patient‐derived organoids (PDOs). Fluorescence‐labeled nanocarriers show efficient uptake by all CRC cells and allow to distinctly track the intracellular trafficking toward endolysosomal compartments. Although free chemotherapeutic drugs exhibit a greater potency in 2D cell cultures, ITC‐FdUMP‐NC demonstrate equivalent cytotoxic efficacies as the freely dissolved drugs in the more complex 3D rectal cancer PDOs. The sustained drug‐release profile of the nanocarriers contrasts favorably with conventional free drugs, potentially enhancing the therapeutic outcome in vivo. With a chemotherapeutic cocktail comparable to the clinically applied FOLFIRI (ITC + 5‐FU), the ITC‐FdUMP‐NC represent a novel type of nanocarrier with high anti‐tumor effect and high drug payload, offering a promising strategy to circumvent chemoresistance and to improve therapy efficacy in vivo with less side effects. [ABSTRACT FROM AUTHOR]

Fe3O4 magnetic nanoparticles exhibit significant potential for cancer detection due to their unique magnetic properties and versatility. This review examines their role in enhancing cancer biomarker detection, focusing on synthesis methods, surface modifications and diagnostic accuracy. Fe3O4 nanoparticles serve as sensitive MRI contrast agents, facilitating early cancer diagnosis and improving patient prognosis. Synthesis techniques influence their properties, morphology and dimensions, which affect performance. Surface modifications enhance targeting and reduce immunological reactions, enabling precise biomarker detection and effective drug delivery to tumours, minimizing damage to healthy tissue. Despite these advantages, challenges remain in optimizing delivery efficiency and overcoming medication resistance. Further research is required to understand the pharmacokinetics and pharmacodynamics of these nanoparticles, including their distribution, metabolism and physiological impacts. This review provides insights into the potential of Fe3O4 magnetic nanoparticles as cancer detection agents, aiming to guide future research towards developing safer and more efficient applications in medical diagnostics and treatment. [ABSTRACT FROM AUTHOR]

The alarming rise in chronic diseases worldwide highlights the urgent need to overcome the limitations of conventional drug delivery systems. In this context, osmotic pumps are able to release drugs by differential osmotic pressure, achieving a controlled rate independent of physiological factors and reducing the dosing frequency. As osmotic pumps are based on the phenomenon of osmosis, the choice of high osmolality draw solutions (DSs) is a critical factor in the successful delivery of the target drug. Therefore, one alternative that has received particular attention is the formulation of DSs with magnetic nanoparticles (MNPs) due to their easy recovery, negligible reverse solute flux (RSF), and their possible tailor-made functionalization to generate high osmotic gradients. In this work, the possible integration of DSs formulated with MNPs in controlled drug delivery systems is discussed for the first time. In particular, the main potential advantages that these novel medical devices could offer, including improved scalability, regeneration, reliability, and enhanced drug delivery performance, are provided and discussed. Thus, the results of this review may demonstrate the potential of MNPs as osmotic agents, which could be useful for advancing the design of osmotic pump-based drug delivery systems. [ABSTRACT FROM AUTHOR]

To overcome chondrosarcoma's (CHS) high chemo- and radioresistance, we used polyethylene glycol-encapsulated iron oxide nanoparticles (IONPs) for the controlled delivery of the chemotherapeutic doxorubicin (IONPDOX) to amplify the cytotoxicity of proton radiation therapy. Human 2D CHS SW1353 cells were treated with protons (linear energy transfer (LET): 1.6 and 12.6 keV/µm) with and without IONPDOX. Cell survival was assayed using a clonogenic test, and genotoxicity was tested through the formation of micronuclei (MN) and γH2AX foci, respectively. Morphology together with spectral fingerprints of nuclei were measured using enhanced dark-field microscopy (EDFM) assembled with a hyperspectral imaging (HI) module and an axial scanning fluorescence module, as well as scanning electron microscopy (SEM) coupled with energy-dispersive X-Ray spectroscopy (EDX). Cell survival was also determined in 3D SW3153 spheroids following treatment with low-LET protons with/without the IONPDOX compound. IONPDOX increased radiosensitivity following proton irradiation at both LETs in correlation with DNA damage expressed as MN or γH2AX. The IONPDOX–low-LET proton combination caused a more lethal effect compared to IONPDOX–high-LET protons. CHS cell biological alterations were reflected by the modifications in the hyperspectral images and spectral profiles, emphasizing new possible spectroscopic markers of cancer therapy effects. Our findings show that the proposed treatment combination has the potential to improve the management of CHS. [ABSTRACT FROM AUTHOR]

Nanofiber hydrogel composites integrate the high water content and biocompatibility of hydrogels with the high surface area-to-volume ratio nano-scale dimensions and ability to mimic the extracellular matrix ECM . This convergence presents promising applications in biomedicine. Advances in biomedical engineering have spurred high expectations for the performance and functionality of composite hydrogels notably in biomimetic materials drug delivery and tissue engineering. Nonetheless traditional nanofiber membranes struggle to replicate complex three-dimensional micro-nano environments. Their small pore sizes and high densities restrict nutrient transport. Furthermore the inadequate dispersion of continuous nanofibers hampers the materials' minimally invasive use. To address these limitations researchers have progressively introduced controllable-length short nanofibers into hydrogel networks. These nanofibers offer superior dispersibility enhancing their integration with hydrogels and the emulation of complex physiological conditions. To comprehensively understand the research status and performance advantages of short nanofiber composite hydrogels and to promote their development and application this paper reviews recent progress. It focuses on the functionalization and composite methods of short nanofibers summarizing their applications in the biomedical field and proposing current challenges and future directions. Functionalized short nanofibers serve crucial roles in composite hydrogels. Firstly by encapsulating cytokines or nanoparticles these fibers create a microenvironment within the hydrogel enhancing cell growth. Secondly surface modifications that immobilize therapeutic or monitoring agents on the fiber surface can prevent drug loss thereby enhancing therapeutic efficacy. Additionally these modifications increase the contact area between the drug and its environment improving detection sensitivity. Furthermore by modifying precursor materials prior to electrospinning short fibers can be functionally customized imparting specific properties and improving compatibility with the hydrogel matrix. The application of biotechnology such as the self-assembly of large molecules like DNA and peptides into short nanofibers not only endows them with specific biological functionality but also enables interaction with hydrogels enhancing their effects and further expanding the potential applications of short fibers in hydrogels. The binding mechanisms between short fibers and hydrogels are crucial. Besides simple physical blending the interfacial interaction between the two can be strengthened through a series of interactions including covalent bonding hydrogen bonding biotin interaction etc. Furthermore methods such as heat treatment mechanical stretching solvent diffusion and magnetic field control can orderly arrange short fibers in gels forming oriented structures which aid in mimicking the microstructure of natural oriented tissues such as muscles and nerves promoting tissue regeneration. The enhancement and functionalization of hydrogels become a significant research focus in biomedical materials science with the innovative incorporation of short fibers offering new pathways for improving hydrogel performance. This approach not only enhances the mechanical properties of hydrogels but also introduces new functionalities in a simple and effective manner. Short fiber-reinforced hydrogels demonstrate extensive potential applications in regulating cellular behavior optimizing drug delivery mechanisms and enhancing biosensing capabilities. These advancements provide a new material foundation and therapeutic strategy for regenerative medicine and precision medicine. However current research on composite hydrogels faces several significant challenges. Firstly the primary fabrication techniques for short nanofibers suffer from scalability issues and inconsistent fiber morphology. Innovative fabrication methods that enhance production efficiency and achieve uniform fiber dimensions are urgently needed. Secondly the precise control of the three-dimensional distribution and orientation of short fibers within the gel matrix is critical for optimizing the performance of composite hydrogels. This necessitates a deeper understanding of interfacial interactions and the development of advanced fiber assembly strategies. Lastly while the incorporation of short nanofibers improves the mechanical properties of composite materials they still fall short of the high-strength requirements for applications such as bone and joint repair. Thus advanced composite strategies that can match or exceed the mechanical properties of natural tissues are essential to ensure long-term stability and functionality in complex biomechanical environments. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to formulate Citrus limon fruit rind's essential oil (EO) and to analyze its impact on breast cancer cells. Materials and Methods: Initially, the cytotoxicity of EO (0.09-9 µg/ml) and doxorubicin (0.5-5 µM) on MCF-7, SK-BR-3, and MDA-MB-231 breast cancer cells was assessed using the MTT assay following 24-72 hr treatment. The cells were then treated with niosomes containing 4.5 µg/ml EO and 0.5 µM doxorubicin for 48 hr. Flow cytometry, migration assay, and RT-qPCR were used to study the cell behavior. Results: MTT results indicated that both EO and doxorubicin alone exhibited severe cytotoxicity (viability ≤ 30%) towards all three cells after 48 hr . When treated with encapsulated EO, the apoptotic death rate in MCF-7, MDA-MB-231, and SK-BR-3 cells was substantially diminished to 14%, 28%, and 9%, respectively. Similarly, encapsulated doxorubicin induced mild apoptotic death in these cells. Encapsulated EO and doxorubicin significantly prevented the migration of all cells. Following treatment with the encapsulated EO, a notable reduction in the expression of VIM, SLUG, SNAIL, and JUN, which are promoters of cancer cell invasion, was seen. Conversely, the expression of the FAS receptor, an active participant in the extrinsic apoptosis pathway, increased (p<0.01). Conclusion: Lemon EO has apoptotic and anti-migratory effects on breast cancer cells, comparable to that of doxorubicin. Utilizing niosome as an efficient delivery modality effectively mitigates the adverse effects of EO and can be used for in vivo delivery of it to cancer cells. [ABSTRACT FROM AUTHOR]

The biosynthesis of bacterial cellulose (BC) is significantly influenced by the type of carbon source available in the growth medium, which in turn dictates the material's final properties. This study systematically investigates the effects of five carbon sources—raffinose (C18H32O16), sucrose (C12H22O11), glucose (C6H12O6), arabinose (C5H10O5), and glycerol (C3H8O3)—on BC production by Komagataeibacter hansenii. The varying molecular weights and structural characteristics of these carbon sources provide a framework for examining their influence on BC yield, fiber morphology, and network properties. BC production was monitored through daily measurements of optical density and pH levels in the fermentation media from day 1 to day 14, providing valuable insights into bacterial growth kinetics and cellulose synthesis rates. Scanning electron microscopy (SEM) was used to elucidate fibril diameter and pore size distribution. Wide-angle X-ray scattering (WAXS) provided a detailed assessment of crystallinity. Selected BC pellicles were further processed via freeze-drying to produce a foam-like material that maximally preserves the natural three-dimensional structure of BC, facilitating the incorporation and release of lidocaine hydrochloride (5%), a widely used local anesthetic. The lidocaine-loaded BC foams exhibited a sustained and controlled release profile over 14 days in simulated body fluid, highlighting the importance of the role of carbon source selection in shaping the BC network architecture and its impact on drug release profile. These results highlight the versatility and sustainability of BC as a platform for wound healing and drug delivery applications. The tunable properties of BC networks provide opportunities for optimizing therapeutic delivery and improving wound care outcomes, positioning BC as an effective material for enhanced wound management strategies. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are gaining interest in regenerative medicine and biomaterials have been shown to extend EV bioavailability following delivery. Herein, the labeling of both hydrogels and EVs is reported to better understand hydrogel design for sustained EV release into tissues. Shear‐thinning hydrogels are engineered using guest–host (i.e., adamantane–cyclodextrin) modifications to hyaluronic acid (GH), as well as GH hydrogels with the addition of gelatin crosslinked via transglutaminase (GH+Gel) to temporally control hydrogel properties. When labeled with a near‐IR dye and injected into rat myocardial tissue, the GH+Gel hydrogel is retained (>14 days) longer than the GH hydrogel alone (≈7 days), likely due to the added gelatin network. To overcome challenges associated with common EV labeling methods, a highly versatile metabolic labeling methodology is utilized via the incorporation of N‐azidoacetylmannosamine‐tetraacylated during EV synthesis to introduce azide groups that can then be reacted with DBCO dyes. When injected in saline, EVs are cleared within 24 h in hearts; however, hydrogels enhance EV retention, with levels based on hydrogel degradation behavior, namely, >14 days for GH+Gel hydrogel and ≈7 days for GH hydrogel alone. These findings support the use of hydrogels in EV therapies. [ABSTRACT FROM AUTHOR]

Salicylate-based poly(anhydride-esters; SAPAEs) have demonstrated wound healing properties due to salicylic acid (SA) release during polymer degradation. Additionally, the polymers are deformable and self-adhesive due to their low Young's modulus, lower glass transition temperature (T g), and inherent tackiness at body temperature. These properties make them particularly well-suited for therapeutic use in the bacteria-laden environment of the oral cavity. To enhance their therapeutic capabilities, the antiseptic chlorhexidine dihydrochloride was physically incorporated into SAPAEs for dual release of antiseptic and anti-inflammatory upon degradation. This study analyzes the thermomechanical properties of two SAPAE compositions (adipate homopolymer and 50:50 adipate:sebacate copolymer) and the release of chlorhexidine (incorporated at 10% (w/w)) from these polymers. Polymer adhesivity was monitored as a function of chlorhexidine incorporation and in vitro degradation time. Throughout in vitro degradation, the polymer systems had a low Young's modulus and a T g at or near body temperature. Incorporation of the antiseptic further decreased Young's modulus and increased both the T g and adhesivity. The release profiles were also evaluated and determined to be similar for the homopolymer and copolymer, although the homopolymer degradation occurred over a longer time period. Overall, the SAPAE systems have favorable properties for periodontal disease treatments by virtue of their controlled degradability, deformability, adhesivity, and release profiles with encapsulated antiseptic. [ABSTRACT FROM AUTHOR]

This study chronicles the seminal contributions of Dr. Raphael M. Ottenbrite, the late Founding Editor of the Journal of Bioactive and Compatible Polymers, to polymer science from the 1970s through 2016. Beginning with an exploration of the biological impacts of anionic polymers, Dr. Ottenbrite's research evolved to include their applications in immunology and cancer therapy. The 1980s marked a pivotal shift toward the synthesis of polymers geared specifically toward biomedical uses. In the 1990s, his work advanced to include sophisticated synthesis methods and surface modification techniques. The 2000s were characterized by a focus on nanotechnology and the innovation of drug delivery systems. His final research phase, from 2011 to 2016, concentrated on the development of biodegradable materials and advanced drug delivery systems. Dr. Ottenbrite's work was a unique blend of polymer chemistry, materials science, and biomedicine, laying a vital groundwork for future interdisciplinary research. [ABSTRACT FROM AUTHOR]

Alpha-lipoic acid (ALA) has garnered significant attention for its potential therapeutic benefits across a wide spectrum of health conditions. Despite its remarkable antioxidant properties, ALA is hindered by challenges such as low bioavailability, short half-life, and unpleasant odor. To overcome these limitations and enhance ALA's therapeutic efficacy, various nanoparticulate drug delivery systems have been explored. This comprehensive review evaluates the application of different nanoparticulate carriers, including lipid-based nanoparticles (solid lipid nanoparticles, niosomes, liposomes, nanostructured lipid carriers (NLCs), and micelles), nanoemulsions, polymeric nanoparticles (nanocapsules, PEGylated nanoparticles, and polycaprolactone nanoparticles), films, nanofibers, and gold nanoparticles, for ALA delivery. Each nanoparticulate system offers unique advantages, such as improved stability, sustained release, enhanced bioavailability, and targeted delivery. For example, ALA-loaded SLNs demonstrated benefits for skin care products and skin rejuvenation. ALA encapsulated in niosomes showed potential for treating cerebral ischemia, a condition largely linked to stroke. ALA-loaded cationic nanoemulsions showed promise for ophthalmic applications, reducing vascular injuries, and corneal disorders. Coating liposomes with chitosan further enhanced stability and performance, promoting drug absorption through the skin. This review provides a comprehensive overview of the advancements in nanoparticulate delivery systems for ALA, highlighting their potential to overcome the limitations of ALA administration and significantly enhance its therapeutic effectiveness. These innovative approaches hold promise for the development of improved ALA-based treatments across a broad spectrum of health conditions. [ABSTRACT FROM AUTHOR]

Objective: Transcatheter Arterial Chemoembolization (TACE) is the first choice for the treatment of advanced-stage hepatocellular carcinoma (HCC). However, TACE suffers from a lack of specificity and rapid drug release. Herein, a targeted redox-responsive peptide (TRRP) was synthesized and used as a carrier of doxorubicin (DOX) to enhance the efficacy of TACE through tumor cells targeting and controlled drug release. Methods: TRRP has a high loading capacity of DOX and a sensitive drug release behavior at high glutathione (GSH) concentration. Moreover, TRRP could bind to the transferrin receptor on the surface of tumor cells, which enhanced the efficacy of TACE and reduced side effects of TACE. TACE with TRRP@DOX dispersed in lipiodol shows an enhanced therapeutic outcome compared to the treatment with DOX + lipiodol emulsion in orthotopic rat HCC models. Results: TRRP has a high loading capacity of DOX and a sensitive drug release behavior at GSH concentration. Moreover, TRRP could bind to the transferrin receptor on the surface of tumor cells, which enhanced the efficacy of TACE and reduced side effects of TACE. TACE with TRRP@DOX dispersed in lipiodol shows an enhanced therapeutic outcome compared to the treatment with DOX + lipiodol emulsion in orthotopic rat HCC models. Conclusions: This study demonstrated that TRRP was a promising therapeutic agent for enhancing TACE therapy for HCC treatment. [ABSTRACT FROM AUTHOR]

In this work, we conceived and developed antibody-drug conjugates (ADCs) that could efficiently release the drug after enzymatic cleavage of the linker moiety by tumoral proteases. The antibody-drug linkers we used are the result of a rational optimization of a previously reported PEGylated linker, PUREBRIGHT® MA-P12-PS, which showed excellent drug loading capacities but lacked an inbuilt drug discharge mechanism, thus limiting the potency of the resulting ADCs. To address this limitation, we chose to incorporate a protease-sensitive trigger into the linker to favor the release of a "PEGless" drug inside the tumor cells and, therefore, obtain potent ADCs. Currently, most marketed ADCs are based on the Val-Cit dipeptide followed by a self-immolative spacer for releasing the drug in its unmodified form. Here, we selected two untraditional peptide sequences, a Phe-Gly dipeptide and a Val-Ala-Gly tripeptide and placed one or the other in between the drug on one side (N-terminus) and the rest of the linker, including the PEG moiety, on the other side (C-terminus), without a self-immolative group. We found that both linkers responded to cathepsin B, a reference lysosomal enzyme, and liberated a PEG-free drug catabolite, as desired. We then used the two linkers to generate ADCs based on trastuzumab (a HER2-targeting antibody) and DM1 (a microtubule-targeted cytotoxic agent) with an average drug-to-antibody ratio (DAR) of 4 or 8. The ADCs showed restored cytotoxicity in vitro , which was proportional to the DM1 loading and generally higher for the ADCs bearing Val-Ala-Gly in their structure. In an ovarian cancer mouse model, the DAR 8 ADC based on Val-Ala-Gly behaved better than Kadcyla® (an approved ADC of DAR 3.5 used as control throughout this study), leading to a higher tumor volume reduction and more prolonged median survival. Taken together, our results depict a successful linker optimization process and encourage the application of the Val-Ala-Gly tripeptide as an alternative to other existing protease-sensitive triggers for ADCs. [Display omitted] • Hydrophilic linkers are necessary to accommodate high drug loadings on antibodies. • The proposed linker features two pendant PEG arms to create a hydrated shell around the drug. • The proposed linker uses a protease-sensitive trigger for controlled "PEGless" drug release. • The linker optimization process led to a DAR 8 ADC active in a xenograft tumor model. [ABSTRACT FROM AUTHOR]

Sonoporation-based delivery has great promise for noninvasive drug and gene therapy. After short-term membrane resealing, the long-term function recovery of sonoporated cells affects the efficiency and biosafety of sonoporation-based delivery. It is necessary to identify the key early biological signals that influence cell fate and to develop strategies for manipulating the long-term fates of sonoporated cells. Here, we used a customized experimental platform with a single cavitating microbubble induced by a single ultrasound pulse (frequency: 1.5 MHz, pulse length:13.33 μs, peak negative pressure: ∼0.40 MPa) to elicit single-site reversible sonoporation on a single HeLa cell model. We used a living-cell microscopic imaging system to trace the long-term fates of sonoporated HeLa cells in real-time for 48 h. Fluorescence from intracellular propidium iodide and Fluo-4 was used to evaluate the degree of sonoporation and intracellular calcium fluctuation (ICF), respectively. Changes in cell morphology were used to assess the long-term cell fates (i.e., proliferation, arrest, or death). We found that heterogeneously sonoporated cells had different long-term fates. With increasing degree of sonoporation, the probability of normal (proliferation) and abnormal fates (arrest and death) in sonoporated cells decreased and increased, respectively. We identified ICF as an important early event for triggering different long-term fates. Reversibly sonoporated cells exhibited stronger proliferation and restoration at lower extents of ICF. We then regulated ICF dynamics in sonoporated cells using 2-APB or BAPTA treatment to reduce calcium release from intracellular organelles and enhance intracellular calcium clearance, respectively. This significantly enhanced the proliferation and restoration of sonoporated cells and reduced the occurrence of cell-cycle arrest and death. Finally, we found that the long-term fates of sonoporated cells at multiple sites and neighboring cells were also dependent on the extent of ICF, and that 2-APB significantly enhanced their viability and reduced death. Thus, using a single HeLa cell model, we demonstrated that regulating intracellular calcium can effectively enhance the proliferation and restoration capabilities of sonoporated cells, therefore rescuing the long-term viability of sonoporated cells. These findings add to our understanding of the biophysical process of sonoporation and help design new strategies for improving the efficiency and biosafety of sonoporation-based delivery. [Display omitted] [ABSTRACT FROM AUTHOR]

Anthocyanins, a type of phenolic compound, are found in plants. They are high-value food and pharmaceutical ingredients with improved health benefits and biological functions. However, there are certain drawbacks to using anthocyanins in the food and pharmaceutical industries, such as low stability and vulnerability to severe environmental conditions such as light, pH, temperature, and oxygen which could have a significant impact on the health-promoting properties. Encapsulation is one of the most preferred processing methods since it helps preserve the health benefits of anthocyanin. Choosing an appropriate strategy entails consideration of processing parameters, equipment availability, and application aims. Electrospun nanofibers were used as a novel platform for anthocyanin encapsulation. Because of their superior properties, they can improve the encapsulation efficiency, bioactivity, and bioaccessibility of anthocyanin. The current review examines the chemical structure of anthocyanin and the principles and advantages of electrospinning as an encapsulating method in depth. Finally, the current limitations and opportunities for advancing electrospinning in food packaging and medicine delivery are explored. [ABSTRACT FROM AUTHOR]

Evodiamine is a bioactive alkaloid extracted from the Evodia rutaecarpa plant. It has various pharmacological effects including anti‐cancer, anti‐bacterial, anti‐obesity, anti‐neurodegenerative, anti‐depressant, and cardiac protective properties. Evodiamine demonstrates potent anti‐cancer activity by inhibiting the proliferation of cancer cells in vitro and in vivo. Despite the health‐promoting properties of evodiamine, its clinical use is hindered by low water solubility, poor bioavailability, and toxicity. Thus, there is a need to develop alternative drug delivery systems for evodiamine to enhance its solubility, permeability, and stability, as well as to facilitate targeted, prolonged, and controlled drug release. Nanocarriers can increase the therapeutic potential of evodiamine in cancer therapy while reducing adverse side effects. To date, numerous attempts have been made through the development of smart nanocarriers to overcome the drawbacks of evodiamine. This review focuses on the pharmacological applications, anti‐cancer mechanisms, and limitations of evodiamine. Various nanocarriers, including lipid‐based nanoparticles, polymeric nanoparticles, cyclodextrins, and so forth, have been discussed extensively for evodiamine delivery. Nano‐drug delivery systems could increase the solubility, bioavailability, stability, and therapeutic efficacy of evodiamine. This review aims to present a comprehensive and critical evaluation of several nano‐formulations of evodiamine for cancer therapy. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

In this study, MOF-74 nanocarriers were coated with sodium alginate (SALG) to enhance physicochemical properties and biocompatibility. Spectroscopic and microscopic analyses showed MOF-74 particle size below 100 nm. Zinc-based MOF-74 nanocarriers (Zn-MOF-74) were developed for doxorubicin (DOX) delivery, achieving high drug loading efficiency (DLE) and drug loading capacity (DLC) as measured by UV–visible spectrometry. Nanocarriers synthesized using zinc acetate (RA-MOF-74) achieved a DLE of 96.5% and a DLC of 19.6%, outperforming those prepared with zinc nitrate (RN-MOF-74) with a DLE of 88.8% and a DLC of 18.3%. Uncoated samples released cargo rapidly at pH 1.5 and significantly at pH 8. In contrast, SALG-coated samples showed reduced release at pH 1.5 and reached 54.2% release at pH 8 due to alginate's physicochemical properties. Drug release from DOX@RA-MOF-74/ALG was significantly slower and more sustained than from uncoated samples. This study demonstrates the potential of SALG-coated RA-MOF-74 as a controlled drug release system for biomedical applications. [ABSTRACT FROM AUTHOR]

Poly(vinyl alcohol) (PVA) based hydrogels have gained more interest in the field of biomaterials because of their many biomedical uses (i.e., wound healing, drug delivery, and tissue engineering) and intrinsic physicochemical and biological characteristics. They can be made using a variety of synthetic techniques, but all of them are very time-consuming. Among them, photopolymerization also referred to as light-induced polymerization, has drawn a lot of attention because of its benefits, which include not requiring the use of solvents, easy and quick network formation, energy efficiency, quick processing, control over both space and time and reliability of crosslinking density and matrix strength. Ultraviolet (UV)-curable hydrogels containing PVA as a main component are gaining interest because of their excellent properties, including biodegradability, biocompatibility, less cytotoxicity and remarkable mechanical strength. This review highlights the significance of UV curable systems and their components, types, advantages and disadvantages of photoinitiators (PIs), UV curable monomers and their structures, properties of UV-cured PVA hybrid hydrogels, and their characterizations and applications in different fields. The photopolymerization mechanisms, tunable properties, and unique advantages of these hydrogels have been explored in detail. Furthermore, it sheds light on recent advancements in PVA-based hydrogels research and future exploration in this domain. [ABSTRACT FROM AUTHOR]

[Display omitted] Breast cancers that overexpress human epidermal growth factor receptor 2 (HER2) have poor prognosis. Moreover, available chemotherapies cause numerous side effects due to poor selectivity. To advance more effective and safer therapies for HER2-positive breast cancer, we explored the fusion of drug delivery technology and immunotherapy. Our research led to the design of immunocubosomes loaded with panobinostat and functionalized with trastuzumab antibodies, enabling precise targeting of breast cancer cells that overexpress HER2. We characterised the nanostructure of cubosomes using small-angle X-ray scattering (SAXS), cryo-transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). Moreover, we confirmed the integrity of the trastuzumab antibodies on the immunocubosomes by Fourier-transform infrared spectroscopy (FTIR) and sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Additionally, we found that panobinostat-loaded immunocubosomes were more cytotoxic, and in an uptake-dependant manner, towards a HER2-positive breast cancer cell line (SKBR3) compared to a cell line representing healthy cells (L929). These results support that the functionalization of cubosomes with antibodies enhances both the effectiveness of the loaded drug and its selectivity for targeting HER2-positive breast cancer cells. [ABSTRACT FROM AUTHOR]

High glucose level, bacterial infection, and persistent inflammation within the microenvironment are key factors contributing to the delay of diabetic ulcers healing, while traditional therapeutic methods generally fail to address these issues simultaneously. Here, we present a spatiotemporally responsive cascade bilayer microneedle (MN) patch for accelerating diabetic wound healing via local glucose depletion and sustained nitric oxide (NO) release for long-term antibacterial and anti-inflammatory effects. The MN patch (G/AZ-MNs) possesses a degradable tip layer loading glucose oxidase (GOx), as well as a dissolvable base layer encapsulating l -arginine (Arg)-loaded nanoparticles (NPs). After wound administration, the base part rapidly dissolved, resulting in prompt separation of the MN tip within the wound tissue, which subsequently responded to the overexpressed matrix metalloproteinase-9 (MMP-9) in diabetic lesions, leading to the responsive release of GOx. The released enzyme catalyzed glucose into gluconic acid and hydrogen peroxide (H 2 O 2), which not only reduced glucose level within the diabetic wound, but also initiated the cascade reaction between H 2 O 2 with the Arg that was released from NPs, thereby achieving continuous production of NO for 7 days. Our findings demonstrate that a single administration of the MN patch could effectively heal non-infected or biofilm-infected diabetic wounds with the multifunctional properties. The spatiotemporally responsive cascade bilayer microneedle patch with long-term antibacterial and anti-inflammatory effects accelerates diabetic wound healing via local glucose depletion and sustained nitric oxide release. [Display omitted] [ABSTRACT FROM AUTHOR]

Treatment of triple-negative breast cancer (TNBC) poses significant challenges due to its propensity for metastasis. A key impediment lies in the suppressive immune microenvironment, which fosters tumor progression. This study introduces an approach employing a dual immune-stimulatory CD73 antibody-polymeric cytotoxic drug complex (αCD73-PLG-MMAE). This complex is designed for targeted eradication of TNBC while modulating tumor immunity through mechanisms such as immunogenic cell death (ICD) and interference with the adenosine signaling pathway. By enhancing antitumor immune responses, this strategy offers a highly effective means of treating TNBC and mitigating metastasis. The complex is synthesized by combining αCD73 with poly(L -glutamic acid) (PLG) grafted Fc binding peptides (Fc-III-4C) and Val-Cit-PAB-monomethyl auristatin E (MMAE), exploiting the affinity between αCD73 and Fc-III-4C. αCD73 selectively targets CD73 molecules on both tumor and immune suppressive cells, thereby inhibiting the adenosine pathway. Meanwhile, Val-Cit-PAB-MMAE, activated by cathepsin B, triggers selective release of MMAE, inducing ICD in tumor cells. In a 4T1 tumor model, αCD73-PLG-MMAE significantly enhances drug accumulation in tumors by 4.13-fold compared to IgG-PLG-MMAE, leading to suppression of tumor growth and metastasis. Furthermore, it synergistically augments the antitumor effects of αPD-1, resulting in a tumor inhibition rate of 92 % as compared to 21 % with αPD-1 alone. This study thus presents a pioneering therapeutic strategy for TNBC, emphasizing the potential of targeted immunomodulation in cancer treatment. Antibody-drug conjugate (ADC) therapy holds promise for treating triple-negative breast cancer (TNBC). However, the current ADC, sacituzumab govitecan, fails to overcome the crucial role of adenosine in the suppressive immune microenvironment characteristic of this "cold tumor". Here, we present a dual immune-stimulatory complex, αCD73-PLG-MMAE, which targets TNBC specifically and modulates tumor immunity through mechanisms such as immunogenic cell death (ICD) and interference with the adenosine signaling pathway. Thus, it kills tumor cells with cytotoxic drugs, comprehensively regulates immunosuppression, and restores a durable immune response. This study proposes an antibody-polymeric drug complex with immunomodulatory and immunoagonist roles, offering new insights into TNBC treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

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In recent decades, nanomedicine has attracted much attention at the forefront of nanotechnology, gaining great expectations in the biomedical sectors. Among various nanomaterials, silica nanoparticles-based drug delivery is considered effective owing to their physicochemical stability and biological compatibility. Surface grafting and chemical conversion techniques were used to create an amphoteric functional ligand known as amidoxime ligand (AL) modified mesoporous silica material (MS-AL NPs). With this technique, amidoxime ligand groups can be introduced in greater concentration to the silica surface without compromising its structure. The active surface allows for surface functionalization and integration of medicinal substances. They are widely employed in the bio-medical industry for diagnostics, target administration of drugs, bio-sensing, cellular absorption, and so on. The function of the produced MS-AL NPs as a regulated drug delivery system was studied utilizing doxorubicin (Dox) as a model anticancer drug. Using the MCF-7 cell line, the biocompatibility and cellular uptake characteristics were investigated. Considering all factors, the MS-AL NPs may be used as pH-responsive drug carriers in cancer treatment applications. [ABSTRACT FROM AUTHOR]

This research aimed to create self‐assembled nanogel particles using chitosan grafted with various types of Pluronic to encapsulate curcumin, a hydrophobic biological agent. The study explored the properties of CS–Pluronic nanogels using Pluronic types L61, P123, F127, and F68, each varying in hydrophilic–lipophilic balance (HLB) index. Findings indicated that the critical micelle concentration (CMC) of Pluronics and CS–Pluronic copolymers did not depend on the HLB values but were influenced by the structural characteristics of each Pluronic type. The efficiency of curcumin encapsulation within the nanogels correlated with the CMC values of the CS–Pluronic copolymers, where lower CMC values resulted in higher encapsulation efficiencies. The curcumin‐loaded nanogels were spherical, positively charged, and had an average diameter under 200 nm. Controlled, pH‐dependent release of curcumin was observed in vitro studies conducted at 37°C in PBS at pH levels of 7.4 and 5.0, with a faster release in acidic conditions. Biocompatibility testing indicated that nanogel biocompatibility was influenced by the HLB value of Pluronic, with lower HLB values associated with reduced biocompatibility. Cytotoxicity testing revealed that curcumin‐loaded nanogels had increased cytotoxicity on MCF‐7 cells compared to free curcumin. CS–P123 emerged as the most effective carrier, meeting biocompatibility and stability requirements during storage. Highlights: CS–Pluronic serves as an effective hydrophobic drug delivery system.The capacity of CS–Pluronic to encapsulate hydrophobic drugs is determined by its CMC value rather than its HLB index.CS–Pluronic is a copolymer known for its excellent biocompatibility.CS–Pluronic increases the toxicity of curcumin in nanogels compared to free curcumin. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) that target multiple transport mechanisms facilitate targeted delivery of active therapeutic agents to the central nervous system (CNS) and improve therapeutic transport and efficacy across the blood‐brain barrier (BBB). CNS nanotherapeutics mostly target neurons and endothelial cells, however, microglial immune cells are the first line of defense against neuronal damage and brain infections. Through triggering release of inflammatory cytokines, chemokines and proteases, microglia can however precipitate neurological damage—a significant factor in neurodegenerative diseases. Thus, microglial inhibitory agents are attracting much attention among those researching and developing novel treatments for neurodegenerative disorders. The most established inhibitors of microglia investigated to date are resveratrol, curcumin, quercetin, and minocycline. Thus, there is great interest in developing novel agents that can bypass or easily cross the BBB. One such approach is the use of modified‐nanocarriers as, or for, delivery of, therapeutic agents to the brain and wider CNS. For microglial inhibition, polymeric NPs are the preferred vehicles for choice. Here, we summarize the immunologic and neuroinflammatory role of microglia, established microglia inhibitor agents, challenges of CNS drug delivery, and the nanotherapeutics explored for microglia inhibition to date. We also discuss applications of the currently considered "most useful" polymeric NPs for microglial‐inhibitor drug delivery in CNS‐related diseases. [ABSTRACT FROM AUTHOR]

One of the major limitations of anti-cancer drugs is their poor selectivity and high toxicity. The present study aims to overcome these difficulties by developing targeted drug delivery systems. Drug delivery systems were synthesized based on magnetite nanoparticles with grafted poly(2-vinylpyridine) from their pre-modified surface with 3-(trimethoxysilyl)propyl methacrylate. The physical and chemical properties of synthesized samples were examined by Fourier-transform infrared spectroscopy, X-ray diffraction, vibrating-sample magnetometry, Energy-dispersive X-Ray analysis and thermogravimetric analysis. The size of nanoparticles was estimated by DLS, final Fe3O4-TMSPM-P2VP-5FU nanoparticles have an average size of 120 nm (PDI is 0.286). Release of 5-FU was examined at different pH (4.5 and 7.58) and constant temperature of 36.6 °C using UV–Vis spectroscopy. [ABSTRACT FROM AUTHOR]

Lignocellulosic biomass is one of the most abundant bioresources on Earth. Over recent decades, various valorisation techniques have been developed to produce value-added products from the cellulosic and hemicellulosic fractions of this biomass. Lignin is the third major component accounting for 10–30% (w/w). However, it currently remains a largely unused fraction due to its recalcitrance and complex structure. The increase in the global demand for lignocellulosic biomass, for energy and chemical production, is increasing the amount of waste lignin available. Approaches to date for valorizing this renewable but heterogeneous chemical resource have mainly focused on production of materials and fine chemicals. Greater value could be gained by developing higher value pharmaceutical applications which would help to improve integrated biorefinery economics. In this review, different lignin extraction methods, such as organosolv and ionic liquid, and the properties and potential of the extracted chemical building blocks are first summarized with respect to pharmaceutical use. The review then discusses the many recent advances made regarding the medical or therapeutic potential of lignin-derived materials such as antimicrobial, antiviral, and antitumor compounds and in controlled drug delivery. The aim is to draw out the link between the source and the processing of the biomass and potential clinical applications. We then highlight four key areas for future research if therapeutic applications of lignin-derived products are to become commercially viable. These relate to the availability and processing of lignocellulosic biomass, technologies for the purification of specific compounds, enhancements in process yield, and progression to human clinical trials. [ABSTRACT FROM AUTHOR]

Cell-mediated nanoparticle delivery systems (CMNDDs) utilize cells as carriers to deliver the drug-loaded nanoparticles. Unlike the traditional nanoparticle drug delivery approaches, CMNDDs take the advantages of cell characteristics, such as the homing capabilities of stem cells, inflammatory chemotaxis of neutrophils, prolonged blood circulation of red blood cells, and internalization of macrophages. Subsequently, CMNDDs can easily prolong the blood circulation, cross biological barriers, such as the blood-brain barrier and the bone marrow–blood barrier, and rapidly arrive at the diseased areas. Such advantageous properties make CMNDDs promising delivery candidates for precision targeting. In this review, we summarize the recent advances in CMNDDs fabrication and biomedical applications. Specifically, ligand-receptor interactions, non-covalent interactions, covalent interactions, and internalization are commonly applied in constructing CMNDDs in vitro. By hitchhiking cells, such as macrophages, red blood cells, monocytes, neutrophils, and platelets, nanoparticles can be internalized or attached to cells to construct CMNDDs in vivo. Then we highlight the recent application of CMNDDs in treating different diseases, such as cancer, central nervous system disorders, lung diseases, and cardiovascular diseases, with a brief discussion about challenges and future perspectives in the end. [ABSTRACT FROM AUTHOR]

Diabetes currently affects approximately 500 million people worldwide and is one of the most common causes of mortality in the United States. To diagnose and monitor diabetes, finger-prick blood glucose testing has long been used as the clinical gold standard. For diabetes treatment, insulin is typically delivered subcutaneously through cannula-based syringes, pens, or pumps in almost all type 1 diabetic (T1D) patients and some type 2 diabetic (T2D) patients. These painful, invasive approaches can cause non-adherence to glucose testing and insulin therapy. To address these problems, researchers have developed miniaturized blood glucose testing devices as well as microfluidic platforms for non-invasive glucose testing through other body fluids. In addition, glycated hemoglobin (HbA1c), insulin levels, and cellular biomechanics-related metrics have also been considered for microfluidic-based diabetes diagnosis. For the treatment of diabetes, insulin has been delivered transdermally through microdevices, mostly through microneedle array-based, minimally invasive injections. Researchers have also developed microfluidic platforms for oral, intraperitoneal, and inhalation-based delivery of insulin. For T2D patients, metformin, glucagon-like peptide 1 (GLP-1), and GLP-1 receptor agonists have also been delivered using microfluidic technologies. Thus far, clinical studies have been widely performed on microfluidic-based diabetes monitoring, especially glucose sensing, yet technologies for the delivery of insulin and other drugs to diabetic patients with microfluidics are still mostly in the preclinical stage. This article provides a concise review of the role of microfluidic devices in the diagnosis and monitoring of diabetes, as well as the delivery of pharmaceuticals to treat diabetes using microfluidic technologies in the recent literature. [ABSTRACT FROM AUTHOR]

Microneedle transdermal administration and low-frequency ultrasound represent two important physical penetration-promoting methods for enhancing drug penetration. This article aims to investigate and compare the effects of drug penetration enhancement through transdermal administration using vibrating microneedles versus low-frequency sonophoresis. In Vitro permeation studies were conducted using Valia-Chien double chamber diffusion cells to evaluate the transdermal delivery of tetramethylpyrazine hydrochloride (TMPH). The TMPH concentration in the receiving compartment was determined using high-performance liquid chromatography (HPLC). Several combinations of microneedles and ultrasound settings were investigated, including different needle heights, vibration frequencies, exposure times, and assorted distances of ultrasound horn and skin. The results revealed the vibrating microneedle system as the most efficacious treatment to increase the TMPH permeability into the rat skin. The combination of a larger needle, higher frequency, and a 3-min exposure led to a 41.92-fold increase in cumulative permeability compared to the control group. The ultrasound treatment exhibited a moderate enhancement effect on TMPH skin penetration. Using a horn-to-skin distance of 3 mm and a 3-min exposure resulted in a 4.34-fold increase in TMPH cumulative permeation compared to the control group. It could be concluded that while both the vibrating microneedle and the low-frequency ultrasound systems act as penetration enhancers for promoting the TMPH permeation through the skin, the vibrating microneedle system notably demonstrates a more effective penetration-promoting effect. System illustrations and permeation effects between vibrating microneedle and low-frequency sonophoresis systems. [ABSTRACT FROM AUTHOR]

The emergence and rapid spread of SARS-CoV-2 in late 2019 prompted a global response from scientists to develop vaccines and therapeutics aimed at preventing the spread of the virus and alleviating its symptoms. The unique properties of nanoparticles make them valuable tools for developing drugs and vaccines against COVID-19, offering the potential to improve the efficacy, safety, and scalability of treatment. As a result, a wide array of vaccines was developed, with nanoparticles playing a crucial role in their formulation. Extensive research has been conducted to explore the potential of nanoparticle-based technologies in combating COVID-19. In this review, we primarily provide a brief overview of COVID-19 and its therapeutics. We then introduce the characteristics of each category of nanoparticles, including metal-, polymer-, lipid-, and carbon-based nanoparticles, with a focus on studies utilizing nanoparticles to fabricate novel vaccines and address the challenges posed by the virus. Additionally, we discuss novel drugs utilizing nanoparticles as delivery vehicles for targeted therapy against COVID-19, highlighting the diverse applications of nanoparticle technology in the battle against the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

The malignant form of melanoma is one of the deadliest human cancers that accounts for almost all of the skin tumor-related fatalities in its later stages. Achieving an exhaustive understanding of reliable cancer-specific markers and molecular pathways can provide numerous practical techniques and direct the way toward the development of rational curative medicines to increase the lifespan of patients. Immunotherapy has significantly enhanced the treatment of metastatic and late-stage melanoma, resulting in an incredible increase in positive responses to therapy. Despite the increasing occurrence of melanoma, the median survival rate for patients with advanced, inoperable terminal disease has increased from around six months to almost six years. The current knowledge of the tumor microenvironment (TME) and its interaction with the immune system has resulted in the swift growth of innovative immunotherapy treatments. Exosomes are small extracellular vesicles (EVs), ranging from 30 to 150 nm in size, that the majority of cells released them. Exosomes possess natural advantages such as high compatibility with living organisms and low potential for causing immune reactions, making them practical for delivering therapeutic agents like chemotherapy drugs, nucleic acids, and proteins. This review highlights recent advancements in using exosomes as an approach to providing medications for the treatment of melanoma. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a highly aggressive bone cancer primarily affecting children, adolescents, and young adults. The current gold standard for treatment of osteosarcoma patients consists of two to three rounds of chemotherapy, followed by extensive surgical intervention from total limb reconstruction to amputation, followed by additional rounds of chemotherapy. Although chemotherapy has advanced the treatment of osteosarcoma significantly, the overall 5-year survival rate in resistant forms of osteosarcoma is still below 20%. The interaction between cancer and the immune system has long been recognized as a critical aspect of tumour growth. Tumour cells within the tumour microenvironment (TME) suppress antitumour immunity, and immunosuppressive cells and cytokines provide the extrinsic factors of tumour drug resistance. Emerging research demonstrates an immunostimulatory role for the cGAS/STING pathway in osteosarcoma, typically considered an immune-cold or immunosuppressed cancer type. cGAS/STING signalling appears to drive an innate immune response against tumours and potentiates the efficacy of other common therapies including chemo and radiotherapy. Nanotechnological delivery systems for improved therapy delivery for osteosarcoma have also been under investigation in recent years. This review provides an overview of cGAS/STING signalling, its divergent roles in the context of cancer, and collates current research which activates cGAS/STING as an adjuvant immunomodulatory target for the treatment of osteosarcoma. It will also discuss current nanotechnological delivery approaches that have been developed to stimulate cGAS/STING. Finally, it will highlight the future directions that we believe will be central to the development of this transformative field. [ABSTRACT FROM AUTHOR]

Triple negative breast cancers (TNBCs) lacking estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) on their cell surfaces are highly aggressive, difficult‐to‐treat and often relapse. Herein, we report on the self‐assembled lipid nanoparticles (LNPs) of two new pegylated lipopeptides for killing TNBCs (MDA‐MB‐231). The pegylated lipopeptides were synthesized by conjugating an n‐hexadecyl hydrophobic tail to one end of a (PEG)27 unit the other distal end of which was covalently grafted with two previously reported tumor targeting RGDK‐ and CGKRK‐ peptides. The SEM images of the self‐assembled LNPs formed upon dissolution of the pegylated lipopeptides in aqueous medium revealed formation of spherical aggregates. The degree of cellular uptake for the self‐assembled LNPs formed by the pegylated CGKRK‐lipopeptide were found to be significantly higher than that for the self‐assembled LNPs formed by the pegylated RGDK‐lipopeptide in MCF‐7, MDA‐MB‐231, HEK‐293 and HFF cells. Notably, about 60 % TNBCs (MDA‐MB‐231 cells) were killed upon treatment with commercially available potent JAK2 inhibitor (WP 1066) loaded LNPs of the pegylated RGDK‐lipopeptide. Contrastingly, the same treatment killed only about 20 % non‐cancerous HEK‐293 cells. The self‐assembled pegylated LNPs described herein open the door for undertaking preclinical studies in animal models for TNBCs. [ABSTRACT FROM AUTHOR]

Microbubbles (MB) are widely used as contrast agents for ultrasound (US) imaging and US‐enhanced drug delivery. Polymeric MB are highly suitable for these applications because of their acoustic responsiveness, high drug loading capability, and ease of surface functionalization. While many studies have focused on using polymeric MB for diagnostic and therapeutic purposes, relatively little attention has thus far been paid to improving their inherent imaging and drug delivery features. This study here shows that manipulating the polymer chemistry of poly(butyl cyanoacrylate) (PBCA) MB via temporarily mixing the monomer with the monomer‐mimetic butyl cyanoacetate (BCC) during the polymerization process improves the drug loading capacity of PBCA MB by more than twofold, and the in vitro and in vivo acoustic responses of PBCA MB by more than tenfold. Computer simulations and physisorption experiments show that BCC manipulates the growth of PBCA polymer chains and creates nanocavities in the MB shell, endowing PBCA MB with greater drug entrapment capability and stronger acoustic properties. Notably, because BCC can be readily and completely removed during MB purification, the resulting formulation does not include any residual reagent beyond the ones already present in current PBCA‐based MB products, facilitating the potential translation of next‐generation PBCA MB. [ABSTRACT FROM AUTHOR]

Liver fibrosis, arising from factors such as viral infections or metabolic disorders, represents an ongoing global health challenge and is a major risk factor for hepatocellular carcinoma. Unfortunately, there are no clinically approved drugs available for its treatment. Recent studies have illuminated the pivotal role of macrophage recruitment in the pathogenesis of liver fibrosis, presenting a potential therapeutic target. Therefore, it holds great promise to develop novel anti‐fibrotic therapies capable of inhibiting this process. Herein, a drug‐loaded biomimetic nanodecoy (CNV‐C) is developed by harnessing genetically engineered cellular vesicles for the treatment of liver fibrosis. CNV‐C is equipped with a C‐C motif chemokine receptor 2 (CCR2)‐overexpressed surface, enabling it to selectively neutralize elevated levels of C‐C motif chemokine ligand 2 (CCL2), thereby reducing macrophage infiltration and the subsequent production of the fibrogenic cytokine transforming growth factor β (TGF‐β). Moreover, curcumin, an anti‐fibrotic agent, is loaded into CNV‐C and delivered to the liver, facilitating its efficacy in suppressing the activation of hepatic stellate cells by blocking the downstream TGF‐β/Smad signaling. This combinational therapy ultimately culminates in the alleviation of liver fibrosis in a mouse model induced by carbon tetrachloride. Collectively, the findings provide groundbreaking proof‐of‐concept for employing genetically modified nanodecoys to manage liver fibrosis, which may usher in a new era of anti‐fibrotic treatments. [ABSTRACT FROM AUTHOR]

In this study, a red seaweed (Solieria robusta) containing ι‐carrageenan (Carr) was used for nanoparticles (NPs) synthesis using silver (Ag) ions. Initially, the ι‐Carr was extracted from S. robusta using the alkali method. The Carr extracted was fractionated into 3 fractions and > 14 kDa fraction showing high yield with maximum sulfate content characterized using Fourier transform infrared (FT‐IR) as ι‐Carr was used for AgNPs synthesis. The synthesized CarrAgNPs were again used for curcumin (Cur) encapsulation. The cytotoxicity of Carr, Cur, CarrAgNPs, and CurCarrAgNPs was evaluated using HeLa cell lines by MTT assay. The CarrAgNPs and CurCarrAgNPs were characterized using UV‐visible spectroscopy, as well as FT‐IR and XRD analysis. The UV‐visible spectrum confirms the CarrAgNPs showing characteristic SPR bands recorded between 344 and 490 nm with broad peak at 430 nm. The shape of the NPs is spherical, arranged in order of seven per chain. The XRD and FT‐IR characteristics confirm the orthorhombic crystal structure of these NPs. Remarkably, Cur‐loaded CarrAgNPs demonstrate potent anticancer properties by maximum reduction of HeLa cell viability after 24 h at 200 μg/mL in pH 7.4 in an MTT assay medium. A significant increase in the cancer cell viability was recorded at high concentrations of CurCarrAgNPs, confirming its less diffusion and dissolution properties and bioavailability due to lipophilic Cur encapsulation, whereas cytotoxicity was increased proportionately by increasing concentrations of Cur, Carr, and CarrAgNPs that confirm a direct relation with size, dissolution, and bioavailability recorded on the basis of cell death in 24 h of introduction at pH 7.4. The cytotoxicity results suggest the potential of Cur, Carr, CarrAgNPs, and CurCarrAgNPs for drug delivery in selective biomedical product developments. This study highlights the versatility and effectiveness of CurCarrAgNPs in cancer therapy by enhancing the efficacy of therapeutic interventions and targeted drug delivery. [ABSTRACT FROM AUTHOR]

This study demonstrates a novel nanostructured drug delivery system utilizing α‐Fe2O3/CuO/CuFe2O4 ternary nanocomposite for effective drug transport in sick tissues. Centella Asiatica plant extract was employed to synthesize the Fe2O3/CuO/CuFe2O4 nanocomposite via sol‐gel auto combustion technique. The structural and morphological characteristics of the nanocomposite were investigated by XRD, FT‐IR, SEM, EDX, and VSM for magnetic properties. The XRD analysis demonstrates the successful synthesis of Fe2O3/CuO/CuFe2O4 nanocomposite with an average crystallite size of 18.393 nm. The antioxidant and antifungal capabilities of this nanocomposite were assessed for its biological activity. A notable inhibitory zone was observed when tested against the Alternaria spp. and Bipolaris sorokiniana fungi. An IC50 value of 109.88 μg/ml was found in the DPPH test, indicating that the nanocomposite exhibited remarkable antioxidant characteristics. Subsequently, metronidazole was encapsulated with a success rate of 55.53 % at pH 1.2, while at pH 7.4 it gained 57.83 %. The drug release of nanocomposite at pH 1.2 after 330 min was 43.41 % and at pH 7.4 after 300 min it was 52.3 %. The results indicate its potential as an excellent candidate for drug delivery. Furthermore, pH was found to be an effective catalyst in the drug loading and release processes. [ABSTRACT FROM AUTHOR]

Nanocarriers are essential for targeted and enhanced drug delivery. However, the use of toxic solvent and the complex of chemical functionalization have seriously limited their clinical translation. Here, a one‐step strategy is developed to direct the self‐assembly of biocompatible core‐shell nanocapsules with tunable surface functionality by microfluidics. Upon rapid mixing and solvent exchange of ethanol with water in a microfluidic device, drug, oil, polymer, and polymer‐PEG‐function co‐precipitate and self‐assemble into core‐shell nanocapsules with desired surface functionality as driven by energy minimization. The prepared PCL‐PEG‐FA core‐shell nanocapsules demonstrate a high encapsulation efficiency and loading capacity and exhibit excellent tumor‐targeting drug delivery performances both in vitro and in vivo via the binding of functional group on the nanocapsule surface with corresponding receptor on the tumor cell membrane. The immune activation in the tumor microenvironment is investigated in detail by flow cytometry and multiplex immunohistochemistry staining to reveal the underlying mechanism for enhanced anti‐tumor performances. The developed strategy is green, facile, versatile, scalable and offers a promising platform for the design of advanced nanocarriers with hierarchical structure and desired function for enhanced drug delivery. [ABSTRACT FROM AUTHOR]

AbstractThis study aims to evaluated the impact of poly(ε-caprolactone) (PCL) microspheres on the pharmacokinetics and pharmacodynamics (PopPK/PD) of 6-methylcoumarin (6MC). For this, PCL microspheres loaded with 6MC were prepared using the emulsification-evaporation method. Particle size, zeta potential, drug loading, and entrapment efficiency were characterised by dynamic light scattering and UV spectrophotometry. In vitro release and pharmacokinetics in Wistar rats were assessed for free and encapsulated 6MC. Anti-inflammatory activity was evaluated using the carrageenan-induced paw edoema model, with PopPK and PopPK/PD models developed. Microspheres showed diameters between 2.9 and 7.1 µm, zeta potentials of −10 to −15 mV, and drug loading of 0.24 mg/mg. Encapsulation efficiency was 45.5% to 75.9%. PopPK models showed enhanced absorption and distribution, with increased anti-inflammatory potency of encapsulated 6MC. PCL microspheres significantly improved the pharmacokinetic and pharmacodynamic profiles of 6MC, enhancing its therapeutic potential for lipophilic drugs. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has emerged as one of the most promising modalities for cancer treatment providing hopes of cancer patients with the significant advantages over traditional antitumor therapy methods. Supramolecular assemblies based on host‐guest interactions have been widely explored in the field of cancer immunotherapy as the delivery systems. A variety of supramolecular materials show unique features for efficient drug encapsulation, targeting delivery and release, which are favorable to activate antitumor immune responses especially through combination of different treatment strategies. In this review article, we summarize the research progresses of supramolecular assemblies via host‐guest interactions for tumor immunotherapy. The construction of various drug delivery systems including hydrogels, liposomes, and polymeric nanoparticles, the drug encapsulation and delivery, as well as advantages and disadvantages are discussed. The perspectives related to future developments in this field are also described. [ABSTRACT FROM AUTHOR]

Effective intratumoral drug penetration is pivotal for successful cancer treatment. However, due to the disrupted capillary networks and poor perfusion in solid tumors, there exist challenges to realize autonomous directional drug penetration and controlled drug release within the tumor. Considering the specificity of glucose within tumor tissue, we draw inspiration from nature and engineer asymmetrical hollow structures exhibiting chemotaxis towards high glucose levels. By incorporating multiple shells into these structures, we enhance the local chemical concentration gradients, thereby improving cellular uptake and precise targeting. The advantages of anisotropic hollow multishell structure (a‐HoMS) can be reflected from the diffusion coefficient and directivity, which increase by 73.4 % and 273 % respectively compared to conventional isotropic hollow spheres, achieving the most linear movement while ensuring the speed of movement. Furthermore, the multi‐level porosity and temporal‐spatial order of a‐HoMS enable sequential drug delivery that inhibits angiogenesis with inducing cell apoptosis. After the eradication of localized tumor cells, the a‐HoMS can automatically migrate to the alive tumor cells under the glucose gradient, inducing another cycle of drug delivery and chemotaxis, resulting in excellent antitumor efficacy. These anisotropic HoMS demonstrate intelligence, adaptability, and precision in tumor therapy, providing valuable insights for programmable treatment within tissues. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has emerged as a pivotal approach for treating various types of cancer, incorporating strategies such as chimeric antigen receptor T-cell (CAR-T) therapy, immune checkpoint blockade therapy, neoantigen peptides, mRNA vaccines, and small molecule modulators. However, the clinical efficacy of these therapies is frequently constrained by significant adverse effects and limited therapeutic outcomes. In recent years, the integration of nanotechnology into cancer immunotherapy has gained considerable attention, showcasing notable advantages in drug delivery, targeted accumulation, controlled release, and localized administration. This review focuses on nanomaterial-based immunotherapeutic strategies, particularly the development and application of nanocarriers such as liposomes, lipid nanoparticles, polymeric nanoparticles, and self-assembling scaffolds. We examine how these strategies can enhance the efficacy of cancer immunotherapy while minimizing adverse effects and analyze their potential for clinical translation. [ABSTRACT FROM AUTHOR]