Efficacy Of Delivery Research Articles

On the Synergistic Effects of Cold Atmospheric Pressure Plasma Irradiation and Electroporation on Cytotoxicity of HeLa Cells

Cold atmospheric plasma (CAP) treatment induces cancer cell death through the generation of reactive oxygen and nitrogen species (RONS). However, the efficacy of RONS delivery into cells remains limited by membrane permeability. Here, we investigated whether combining CAP with pulsed electric fields (PEFs) could enhance cancer cell death through increased intracellular RONS uptake. HeLa cells were treated with argon atmospheric pressure plasma jet (Ar-APPJ), PEF, or their combination. The combined treatment showed significantly enhanced cell death compared to single treatments. While PEF treatment alone induced membrane permeabilization, the combination with Ar-APPJ resulted in more pronounced and sustained membrane disruption, as evidenced by increased calcein leakage. This enhanced effect was attributed to Ar-APPJ-induced lipid peroxidation interfering with membrane resealing after PEF-induced electroporation. We also demonstrated that PEF-induced membrane electroporation facilitates the intracellular uptake of CAP-generated RONS. These findings provide mechanistic insights into the synergistic effects of combined CAP and PEF treatments, suggesting enhanced cell death via multiple pathways.

Amphiphilic Polyaspartamide Derivatives with Cholesterol Introduction Enhanced Ex Vivo mRNA Transfection Efficiency to Natural Killer Cells.

Engineered natural killer (NK) cells eliminate cancer cells by overexpressing a chimeric antigen receptor, producing highly efficient and safe NK cell therapies. This study investigated the polyplex formulation for the fusion protein GreenLantern-natural killer group 2D (NKG2D) mRNA to evaluate its ex vivo delivery efficacy into NK cells, wherein NKG2D on the surface of NK cells recognized its counterpart NKG2D ligands on cancer cells. Amphiphilic polyaspartamide derivatives Chol-PAsp(DET/CHE) were prepared by adding cyclohexylethylamine (CHE) and diethylenetriamine (DET) in the side chains and cholesterol (Chol) at the α-terminus to enhance endosomal escapability and optimize hydrophobicity. Chol-PAsp(DET/CHE) significantly improved mRNA delivery efficacy into NK-92mi cells, explained by increased polyplex stability and improved cellular uptake of mRNA. The NKG2D-overexpressing NK-92mi cells exhibited high anticancer efficacy against human colon cancer cells without affecting the viability of fibroblasts. Therefore, Chol-PAsp(DET/CHE) could be a promising mRNA delivery carrier for the ex vivo engineering of NK cells.

Stimuli-Responsive Nano Drug Delivery Systems for the Treatment of Neurological Diseases.

Nanomaterials with unparalleled physical and chemical attributes have become a cornerstone in the field of nanomedicine delivery. These materials can be engineered into various functionalized nanocarriers, which have become the focus of research. Stimulus-responsive nanodrug delivery systems (SRDDS) stand out as a sophisticated class of nanocarriers that can release drugs in response to environmental cues. Due to the complex pathogenesis and the multifaceted pathological environment of the nervous system, developing accurate and effective drug therapy with low side-effects is a formidable task. In recent years, SRDDS have been widely used in the treatment of neurological diseases. By customizing SRDDS to align with the specific microenvironment of the nervous system tissues or external stimulation, the efficacy of drug delivery can be enhanced. This review provides an in-depth look at the characteristics of the microenvironment of neurological diseases and highlights case studies of SRDDS tailored to treat these disorders based on theunique stimulation criteria of nervous system tissues or external triggers. Additionally, this review provides a comprehensive overview of the progress and future prospects of SRDDS technology in the treatment of neurological diseases, providing valuable guidance for its transition from fundamental research to clinical application.

A Comprehensive Review of Innovations for Diabetic Retinopathy and Next-generation Intraocular Drug Delivery

Diabetic Retinopathy (DR) is a significant cause of blindness worldwide, particularly in individuals with diabetes. Early diagnosis and intervention are critical in preventing vision loss. However, existing treatments, including anti-VEGF therapies and laser photocoagulation, present several challenges such as frequent injections, side effects, and difficulties in targeting the root causes of the disease. This systematic review examines the innovations in intraocular drug delivery systems for treating DR, focusing on advancements such as sustained-release implants, nanotechnology-based approaches, and gene therapy. These emerging technologies aim to overcome barriers like the blood-retinal barrier (BRB) and improve the efficacy of drug delivery to the retina. Sustained-release systems offer the potential for reducing injection frequency, while nanoparticles and liposomes enhance drug targeting and bioavailability. Gene therapy, which delivers therapeutic genes directly to retinal cells, represents a novel approach to addressing the underlying mechanisms of DR. Despite these promising developments, challenges remain, including improved drug targeting, patient compliance, and long-term safety. The review also highlights the need for interdisciplinary research and the integration of advanced technologies, such as artificial intelligence, in enhancing DR treatment. Future studies should optimise these drug delivery platforms, explore combination therapies, and develop personalised treatment strategies to improve patient outcomes. Overall, the next generation of drug delivery systems holds great promise in transforming the management of Diabetic Retinopathy and preventing its progression to vision-threatening stages.

Chitosan and hyaluronic acid in breast cancer treatment: Anticancer efficacy and nanoparticle and hydrogel development.

The pervasive global health concern of breast cancer necessitates the development of innovative therapeutic interventions to enhance efficacy and mitigate adverse effects. Chitosan and hyaluronic acid, recognized for their biocompatibility and biodegradability, present compelling options for novel drug delivery systems and therapeutic platforms in the context of breast cancer management. This discourse will delineate the distinctive attributes of chitosan and hyaluronic acid, encompassing their inherent anticancer properties, targeting capabilities, and suitability for chemical modifications. These characteristics render them exceptionally well-suited for the fabrication of nanoparticles and hydrogels. The intrinsic anticancer potential of chitosan, in conjunction with its mucoadhesive properties, and the robust binding affinity of hyaluronic acid to CD44 receptors, facilitate precise and efficacious drug delivery to malignant cells, thus circumventing the limitations inherent in conventional treatment modalities. The incorporation of these materials into nanocarriers allows for the concurrent delivery of therapeutic agents, thereby potentiating synergistic effects, while hydrogel systems provide localized, controlled drug release and facilitate tissue regeneration. An analysis of advancements in their synthesis, functionalization, and application is presented, while also acknowledging challenges pertaining to scalability and clinical translation.

Microneedle patch-involved local therapy synergized with immune checkpoint inhibitor for pre- and post-operative cancer treatment.

The metastasis and recurrence of cancer post-surgery remain the major reasons for treatment failures. Herein, a photo-immune nanoparticle decorating with M1 macrophage membrane (BD@LM) is designed based on the inflammatory environment after surgical resection. By loading photosensitizer black phosphorus quantum dots (BPQDs) and chemotherapeutics doxorubicin (DOX) in BD@LM nanoparticles, an effective chemophototherapy-mediated immunogenic cell death of tumor cells is triggered, subsequently leading to the maturation of dendritic cells for further immune cascade. Moreover, by accommodating BD@LM in a dissolvable microneedle patch, the skin barrier is directly broken for efficacious delivery of BD@LM into solid tumors, which boosts the effectiveness of aPD-L1-based checkpoint blockade therapy. Consequently, the growth of both orthotopic and post-surgical breast tumor and melanoma is significantly inhibited. Specifically, an effective T cell activation accompanied with dramatic inhibition of immunosuppressive cells is observed. Meanwhile, the proportion of memory T cells remarkably grows after proposed treatment, indicating the establishment of a long-term immune memory effect for prevention of second tumor attack. Altogether, this work offers a meaningful strategy by combining photo-immune-inspired nanoparticles with microneedle patches for boosting aPD-L1-based tumor immunotherapy.

Enhanced mRNA delivery via incorporating hydrophobic amines into lipid nanoparticles.

Lipid nanoparticles (LNPs) have shown promising performance in mRNA delivery. Nevertheless, a thorough understanding of the relationship between mRNA delivery efficacy and the structure of LNPs remains imperative. In this study, we systematically investigated the effects of additional hydrophobic amines on the physicochemical properties of mRNA LNPs and their delivery efficacy. The results indicated that this influence depended on the chemical structure of the additional amines and the structure of the lipid carriers. The appropriate addition of the hydrophobic amine 2C8 to lipid carriers with structural 2C8 or 2C6 tails significantly increased their mRNA delivery efficiency. In contrast, the addition of hydrophobic amine C18 to LNPs resulted in a decrease in mRNA delivery efficiency, while the addition of hydrophobic amines 2C6 and C8, as well as alkanes C12' and C16', had relatively little effect on mRNA delivery. Further investigations demonstrated that the appropriate addition of 2C8 could reduce LNP size, moderate internal hydrophobicity and LNP stability, facilitate mRNA release, enhance cellular uptake, and improve intracellular transportation of LNPs, thereby achieving superior mRNA delivery efficiency. These findings highlight the important role of additional hydrophobic amines in mRNA delivery with LNPs and provide valuable insights for the advancement of mRNA delivery carriers.

Smart core-shell microneedles for psoriasis therapy: In situ self-assembly of calcium ion-coordinated dexamethasone hydrogel.

Psoriasis is a prevalent relapsing dermatological condition that often necessitates lifelong treatment. The distinctive thickening of the stratum corneum presents a challenge to drug penetration. The employment of microneedles has been demonstrated to enhance the transdermal drug delivery efficacy by creating multiple microchannels in the skin. Nevertheless, polymeric microneedles often encounter difficulties in meeting the requirements for sustained drug release. It is imperative to acknowledge that sustained-release hydrogel microneedles are invariably fabricated under harsh crosslinking conditions. In addressing these challenges, a core-shell microneedles (CSMNs) system was customized at a facile, accessible process, enabling the in situ formation of supramolecular microhydrogels within the skin. This concept was realized by leveraging the interaction between the therapeutic drug dexamethasone sodium phosphate (DexP) and calcium chloride (CaCl2), combined with the differential biphasic release technology (DexP HMNs). Upon insertion into the skin, the core of the microneedles rapidly released CaCl2, which diffused to the shell and formed a hydrogel with DexP, creating multiple reservoirs for the sustained release of DexP. In vitro transdermal permeation experiments demonstrated that DexP HMNs greatly prolonged the skin retention time of DexP. In the context of psoriasis treatment, DexP HMNs were demonstrated to be more effective than DexP CSMNs in inhibiting keratinocyte proliferation and significantly reducing the levels of inflammatory factors and immune cell infiltration at the lesion site. This study provides a new direction for the development of intelligent microneedle drug delivery systems for sustained drug release and enhanced management of chronic skin diseases.

Drug-Loaded Hydrogel Microneedles for Sustainable Transdermal Delivery of Macromolecular Proteins.

Poly(methyl vinyl ether co-maleic acid) (PMVE/MA) hydrogel microneedles (HMN) are investigated for transdermal delivery of macromolecular drugs owing to their biocompatibility and super-swelling properties. However, the drug delivery efficacy reduces with increasing molecular weight due to the entrapment within the HMN matrices. Furthermore, integrating external drug reservoirs extends the drug diffusion path and reduces the efficiency of drug permeation. A direct drug loading approach in the HMN matrix was introduced in this work following a pH modification step. The effect of pH modification on the physicochemical properties of HMN was studied. Then, bovine serum albumin (BSA), a model protein, was loaded into the pH-modified HMN, and the morphological changes in HMN and protein stability were also assessed. Finally, the efficacy of BSA-loaded HMN in the transdermal delivery was evaluated ex vivo. A significant increase in swelling was recorded following the pH modification of HMN (p < 0.001). The structure of pH-modified hydrogel was highly porous, and ATR-FTIR spectra indicated a shift in the carboxylic peak. The secondary structure of BSA loaded in the pH-modified HMN was also preserved. The BSA-loaded HMN mediated a sustained ex-vivo drug release with a cumulative release of 64.70% (3.88 mg) in 24 h. Hence, the model drug-incorporated PMVE/MA HMN system shows potential for sustainable transdermal delivery of proteins.

Rational Design of Dual-Targeted Nanomedicines for Enhanced Vascular Permeability in Low-Permeability Tumors.

Designing dual-targeted nanomedicines to enhance tumor delivery efficacy is a complex challenge, largely due to the barrier posed by blood vessels during systemic delivery. Effective transport across endothelial cells is, therefore, a critical topic of study. Herein, we present a synthetic biology-based approach to engineer dual-targeted ferritin nanocages (Dt-FTn) for understanding receptor-mediated transport across tumor endothelial cells. By leveraging a genetically engineered logic-gated strategy, we coassembled various Dt-FTn in E. coli with tunable ratios of RGD-targeting and intrinsic TfR1-targeting ligands. These Dt-FTn constructs were employed to investigate the interaction between receptor-mediated vascular permeability and dual-targeted nanomedicines in low-permeability tumors. Through machine learning-based single vessel analysis, we uncovered the crucial role of dual-receptor expression profiles in determining the vascular transport of dual-targeted nanomedicines in tumors with low permeability. Using a patient-derived colon cancer model, we demonstrated a proof-of-concept that the optimal proportions of dual ligands in these nanomedicines can be customized based on tumor cell receptor expression profiles. This study provides valuable insights and guiding principles for the rational design of dual-targeted nanomedicines for tumor-targeted delivery.

Lipid Nanoparticles in Medicine: Advances in Diagnostics, Therapeutics, and Future Directions

Abstract Lipid nanoparticles (LNPs) have become a critical tool in modern medicine, particularly in diagnostics and therapy. Various synthesis techniques, including ultrasonication, high-pressure homogenization, solvent evaporation, and microemulsion, have been employed to produce nanoparticles with desired properties. Modification techniques such as surface functionalization, polymer coating, PEGylation, and ligand conjugation further enhance their efficacy and biocompatibility. This study highlights the recent advances in the application of LNPs for improving diagnostic accuracy and therapeutic outcomes. In diagnostics, LNPs enhance visualization, bioimaging, and analytical methods, especially through genomic, proteomic, and immunoassay-based techniques, as well as plasmonic biosensors. In therapy, LNPs are utilized in innovative treatments such as plasmonic photothermal and photodynamic therapies, antibacterial applications, and drug delivery systems. These nanoparticles serve as effective carriers for drugs, genes, and antibodies, improving targeted delivery and therapeutic efficacy. Despite their promising potential, challenges related to safety, scalability, and long-term impacts remain, and this research outlines future perspectives on overcoming these barriers to further integrate LNPs into clinical applications.

BRD4-targeted photodegradation nanoplatform for light activatable melanoma therapy.

The targeted protein degradation (TPD) strategy modulates tumor growth pathways by degrading proteins of interest (POIs) and has reshaped anti-tumor drug research and development. Recently, the emergence of photodegradation-targeting chimeras (PDTACs) and laser irradiation at specific sites enables precise spatiotemporal controllability of TPD. Capitalizing on the advances of PDTACs, herein, we report a nanoplatform for efficiently delivering PDTAC molecule for photodegradation of bromodomain-containing protein 4 (BRD4) proteins, the key activators of oncogenic transcription. The PDTAC molecule, named as PPa-JQ1, is synthesized through the covalent attachment of the BRD4-targeting ligand JQ1-acid, to the photosensitizer pyropheophorbide-a (PPa), utilizing a 1,6-hexanediamine linker. The PPa-JQ1 is further encapsulated by human serum albumin (HSA) to obtain the HSA@PPa-JQ1 nanoplatform, which facilitates targeted and efficacious delivery to melanoma lesions. Both in vitro and in vivo therapeutic outcomes demonstrate that HSA@PPa-JQ1 can efficiently generate reactive oxygen species (ROS) to degrade BRD4 upon light irradiation, which eventually induces tumor death. Our study represents the first case to validate the anti-tumor therapeutic efficacy of PDTACs by systemic administration, providing the foundation for further application of PDTACs.

Emerging Combinatorial Drug Delivery Strategies for Breast Cancer: A Comprehensive Review.

Breast cancer remains the second most prevalent cancer among women in the United States. Despite advancements in surgical, radiological, and chemotherapeutic techniques, multidrug resistance continues to pose significant challenges in effective treatment. Combination chemotherapy has emerged as a promising approach to address these limitations, allowing multiple drugs to target malignancies via distinct mechanisms of action. Increasingly, the use of phytoconstituents alongside chemotherapeutic agents has shown promise in enhancing treatment outcomes. This combination therapy acts on key signaling pathways such as Hedgehog, Notch, Wnt/β- catenin, tyrosine kinases, and phosphatidylinositol 3-kinase (PI3K), which play critical roles in cellular proliferation, apoptosis, angiogenesis, differentiation, invasion, and metastasis. This review explores various signaling pathways involved in breast cancer progression, discusses conventional treatment methods like surgery, adjuvant radiotherapy, hormonal therapy, and chemotherapy, and highlights emerging nanocarrier-based drug delivery systems (DDS). Liposomes, dendrimers, exosomes, polymeric micelles, and nanoparticles (organic, inorganic, gold, magnetic, carbon-based, and quantum dots) are examined as innovative strategies for enhancing drug delivery efficacy. Furthermore, stimuli-responsive DDSs, including reactive oxygen species (ROS), enzyme-, and hypoxia- responsive systems, are presented as cutting-edge approaches to overcoming drug resistance. Special emphasis is placed on the co-delivery of chemotherapeutic agents and plant-based compounds, particularly in estrogen receptor-positive (ER+) breast cancer. This review aims to provide a comprehensive overview of novel combinatorial strategies and advanced nanocarriers for the effective and targeted treatment of breast cancer.

Inhalable Mucociliary-On-Chip System Revealing Pulmonary Clearance Dynamics in Nanodrug Delivery.

The development of a inhaled nanodrug delivery assessment platform is crucial for advancing treatments for chronic lung diseases. Traditional in vitro models and commercial aerosol systems fail to accurately simulate the complex human respiratory patterns and mucosal barriers. To address this, we have developed the breathing mucociliary-on-a-chip (BMC) platform, which replicates mucociliary clearance and respiratory dynamics in vitro. This platform allows for precise analysis of drug deposition and penetration, providing critical insights into how liposomes and other nanocarriers interact with lung tissues under various airflow conditions. Our results reveal that liposomes penetrate deeper into the cellular layer under high shear stress, with both static and dynamic airflows distinctly affecting their drug release rates. The BMC platform integrates dynamic inhalation systems with mucociliary clearance functionality, enabling a comprehensive evaluation of drug delivery efficacy. This approach highlights the importance of airflow dynamics in optimizing inhalable nanodrug delivery systems, improving nanocarrier design, and tailoring drug dosages and release strategies. The BMC platform represents a significant advancement in the field of inhaled nanodrug delivery, offering a more accurate and reliable method for assessing the performance of therapies. By providing a detailed understanding of drug interactions with lung tissues, this platform supports the development of personalized inhaled therapies and offers promising strategies for treating pulmonary diseases and advancing nanodrug development.

Frondoside A of Cucumaria frondosa (Gennerus, 1767): Chemistry, biosynthesis, medicinal applications, and mechanism of actions.

Cucumaria frondosa (Gennerus, 1767) or orange-footed sea cucumbers are traditional food and are used as natural sources of anti-diabetic, anti-inflammatory, antioxidant, anti-angiogenic, antimicrobial, and anticancer agents. Currently, the introduction of value-added sea cucumber products to the global market has inspired basic research on frondoside A and other saponins in sea cucumbers. These saponins serve as a means of their chemical defence. However, recent studies revealed that exposure to these saponins can lead to irritating symptoms from aerosolization of various holothurins. Moreover, extraction methods are critical to the bioavailability of various bioactive compounds found in sea cucumbers. Therefore, we have critically reviewed recent studies on the chemistry, biosynthesis, and pharmacological properties of frondoside A. Furthermore, the mechanism of actions of frondoside A was postulated and further studies are required for applications in functional foods, nutraceuticals, and pharmaceuticals. Frondoside A was first discovered from Cucumaria frondosa, and it is involved in protein kinase (PI3K/AKT/ERK1/2/p38 MAPK, RAC/CDC42 PAK1, NFκB/MAPK/JNK, and LXR-β) signalling pathways. It is also involved in the suppression of MYC oncogene transcriptional factors implicated and upregulated in over 70% of cancer types. Future research needs to be aimed at optimized green extraction techniques, efficient delivery methods, safety, and efficacy.

Intelligent Hierarchical Targeting Near-Infrared Persistent Luminescence Nanosystem for Improved Nuclear Delivery and Simultaneous Visualization/Therapy of EBV-Associated Cancer.

Epstein-Barr nuclear antigen 1 (EBNA1), a sequence-specific DNA binding protein of Epstein-Barr virus (EBV), is essential for viral genome replication and maintenance and is therefore an attractive target for the therapeutic intervention of EBV-associated cancers. Several EBNA1-specific inhibitors have demonstrated the ability to block EBNA1 function in vitro, but practical delivery strategies for these inhibitors in vivo are still lacking. Here, we report an intelligent hierarchical targeting theranostic nanosystem (denoted as mZGOCS@MnO2-P5) that integrates an azide (N3) terminal dual-targeting peptide (N3-P5), a tumor microenvironment-responsive degradable MnO2 nanosheet, and a mesoporous ZnGa2O4:Cr3+, Sn4+ near-infrared persistent luminescence (NIR-PL) nanosphere (mZGOCS). In our design, mZGOCS@MnO2-P5 enables primarily targeting of the EBV-specific oncoprotein LMP1 (an EBV-encoded transmembrane protein) via the LMP1 targeting motif within P5. Once internalized into cells, the MnO2 nanosheet would be degraded in the acidic and reducing tumor microenvironment, simultaneously releasing P5 and recovering the NIR-PL of ZnGa2O4:Cr3+, Sn4+ initially quenched by the MnO2 nanosheet, thereby providing an autofluorescence interference-free NIR-PL imaging signal for monitoring the delivery efficacy of P5. The released P5 can secondarily target EBNA1 via the EBNA1 binding motif, blocking its function and thus inhibiting the growth of EBV-positive tumors. The feasibility of our developed hierarchical targeting theranostic nanosystem is well demonstrated both in vitro and in vivo, highlighting the huge translational potential of mZGOCS@MnO2-P5 in EBV-associated cancer therapy.

In Situ Gelling Dexamethasone Oromucosal Formulation: Physical Characteristics Influencing Drug Delivery.

The study focuses on the development of an in situ gelling dexamethasone (DEX) oromucosal formulation designed for the treatment of aphthous stomatitis. Three series of formulations were prepared; a first series containing DEX suspended, a second series containing DEX and, in addition, mint essential oil (EO), and a third series containing EO and DEX solubilized in propylene glycol (PG). In the composition, polymers in the role of mucoadhesive agent were interchanged (hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), methyl cellulose (MC), carboxymethyl cellulose (CMC), and sodium carboxymethyl cellulose (NaCMC). Specifically, DEX was incorporated at a concentration of 0.1% (w/w) in each formulation. The influence of mint EO and DEX solubilization on the physical properties (pH measurements, rheological analysis, swelling ability, and texture analysis) and in vitro drug release was studied. Key findings revealed that HPMC-based formulation containing mint EO and PG exhibited best swelling properties (700 ± 46% after 5 h), adequate adhesiveness and in vitro drug release (34.7 ± 5.9%). Furthermore, the irritation potential assessed via the hen's egg test on the chorioallantoic membrane (HET-CAM) demonstrated low irritancy risk. Finally, Fourier-transform infrared spectroscopy (FT-IR) showed no incompatibility between DEX and excipients. Overall, the research highlights the potential of mucoadhesive systems in improving the therapeutic efficacy of oromucosal drug delivery for managing painful oral lesions.

Enhanced Transcriptional Activation in Developing Mouse Photoreceptors.

Retinal development in the mouse continues past birth and provides a widely used model system in which photoreceptor formation can be observed and manipulated. This experimental paradigm provides opportunities for both gain-of-function and loss-of-function studies, which can be accomplished through in vivo or ex vivo plasmid delivery and electroporation. However, the cis-regulatory elements used to implement this approach have not been fully evaluated or optimized for the unique transcriptional environment of photoreceptors. Here we investigate whether the use of a photoreceptor cis-regulatory element from the Crx gene in combination with broadly active promoter elements can increase the targeting of developing photoreceptors in the mouse. This study characterizes the in vivo activity of this element for the first time, as well as explores its use as a tool for gain-of-function and loss-of-function experiments. We report that a cis-regulatory element from the Crx gene, in combination with broadly active promoter elements, increases the targeting of developing rod photoreceptors in the mouse. Additionally, the same element can be used to target developing cones at embryonic time points by ex vivo electroporation. Utility of this combined element includes greater reporter expression, as well as enhanced overexpression and loss-of-function phenotypes in photoreceptors. This study highlights the importance of identifying and testing relevant cis-regulatory elements when planning cell subtype-specific experiments. The use of specific hybrid elements will provide a more efficacious gene delivery system to study mammalian photoreceptor formation, which will benefit research with potential therapeutic relevance for blinding diseases.

Advances in the preparation, applications, challenges, and future trends of polysaccharide-based gels as food-grade delivery systems for probiotics: A review.

Probiotics are highly regarded for their multiple functions, such as regulating gut health, enhancing the immune system, and preventing chronic diseases. However, their stability in harsh environments and targeted release remain significant challenges. Therefore, exploring effective protection and delivery strategies to ensure targeted release of probiotics is critically important. Polysaccharides, known for their non-toxicity, excellent biocompatibility, and superior biodegradability, show broad prospects in probiotic delivery by forming physical barriers to protect the probiotics. Particularly, polysaccharide-based gels (PBGs), with their unique "spider-web" like structure, capture and ensure the targeted release of probiotics, significantly enhancing their efficacy. This review discusses common polysaccharides used in PBG preparation, their classification and synthesis in food applications, and the advantages of PBGs as probiotic delivery systems. Despite their potential, challenges such as inconsistent gel properties and the need for improved stability remain. Future research should focus on developing novel PBG materials with higher biodegradability and mechanical strength, optimizing the physicochemical properties and cross-linking methods, as well as designing multilayered structures for more precise release control. Additionally, exploring the co-delivery of probiotics with prebiotics, active ingredients, or multi-strain systems could further enhance the efficacy of probiotic delivery.

Role of Nanotechnology in Ischemic Stroke: Advancements in Targeted Therapies and Diagnostics for Enhanced Clinical Outcomes.

Each year, the number of cases of strokes and deaths due to this is increasing around the world. This could be due to work stress, lifestyles, unhealthy food habits, and several other reasons. Currently, there are several traditional methods like thrombolysis and mechanical thrombectomy for managing strokes. The current approach has several limitations, like delayed diagnosis, limited therapeutic delivery, and risks of secondary injuries. So, there is a need for some effective and reliable methods for the management of strokes, which could help in early diagnosis followed by the treatment of strokes. Nanotechnology has played an immense role in managing strokes, and recently, it has emerged as a transformative solution offering innovative diagnostic tools and therapeutic strategies. Nanoparticles (NPs) belonging to several classes, including metallic (metallic and metal oxide), organic (lipids, liposome), and carbon, can cross the blood-brain barrier and may exhibit immense potential for managing various strokes. Moreover, these NPs have exhibited promise in improving imaging specificity and therapeutic delivery by precise drug delivery and real-time monitoring of treatment efficacy. Nanomaterials like cerium oxide (CeO2) and liposome-encapsulated agents have neuroprotective properties that reduce oxidative stress and promote neuroregeneration. In the present article, the authors have emphasized the significant advancements in the nanomedicine management of stroke, including NPs-based drug delivery systems, neuroprotective and neuroregenerative therapies, and multimodal imaging advancements.