Carriers For Delivery Research Articles

Recent development of micro-nano carriers for oral antineoplastic drug delivery.

Chemotherapy is widely recognized as a highly efficacious modality for cancer treatment, involving the administration of chemotherapeutic agents to target and eradicate tumor cells. Currently, oral administration stands as the prevailing and widely utilized method of delivering chemotherapy drugs. However, the majority of anti-tumor medications exhibit limited solubility and permeability, and poor stability in harsh gastrointestinal environments, thereby impeding their therapeutic efficacy for chemotherapy. Therefore, more and more micro-nano drug delivery carriers have been developed and used to effectively deliver anti-cancer drugs, which can overcome physiological barriers, facilitate oral administration, and ultimately improve drug efficacy. In this paper, we first discuss the effects of various biological barriers on micro-nano drug carriers and oral administration approach. Then, the development of micro-nano drug carriers based on various biomedical components, such as micelles, dendrimers, hydrogels, liposomes, inorganic nanoparticles, etc. were introduced. Finally, the current dilemma and the potential of oral drug delivery for clinical treatment were discussed. The primary objective of this review is to introduce various oral delivery methods and serve as a point of reference for the advancement of novel oral delivery carriers, with the ultimate goal of informing the development of future clinical applications.

Corosolic acid derivative-based lipid nanoparticles for efficient RNA delivery

Lipid nanoparticles (LNPs) represent the most widely employed and clinically validated platform for in vivo RNA delivery. However, currently used LNP formulations, which consist of lipids and cholesterol, exhibit limited transfection efficiency and off-target hepatic transfection. These limitations necessitate higher dosage and pose potential safety concerns. In this study, three derivatives of corosolic acid (CA) were synthesized to create a library of cholesterol-free lipid nanoparticles, CAxLNPs. From this library, CAβLNP was identified as the most effective, exhibiting enhanced tumor cell uptake and superior endosomal membrane fusion capabilities compared to cholesterol-containing LNP formulations, leading to optimal endosomal escape and efficient cytoplasmic delivery of mRNA/siRNA. Following intratumoral injection, CAβLNP demonstrated significantly improved retention and penetration within tumor tissues while minimizing undesired hepatic transfection. This LNP formulation offers a safer, more effective carrier for RNA delivery, providing promising potential to expand the applications of RNA therapeutics.

Retrograded starch as colonic delivery carrier of taxifolin for treatment of DSS-induced ulcerative colitis in mice.

Taxifolin, a natural dihydroflavonol compound, possesses notable anti-inflammatory properties and regulatory effects on intestinal microbiota. In this study, gelatinized-retrograded corn starch (GCS) was utilized as a carrier for colonic delivery of taxifolin, and its therapeutic efficacy against dextran sulfate sodium (DSS)-induced colitis in mice were systematically investigated. Taxifolin can integrate into the helical structure of starch, and the formation of GCS-Taxifolin complexes (GCS-Tax) significantly delayed the release of taxifolin in vitro. After oral administration of GCS-Tax, fecal excretion of taxifolin increased from 0.42% to 10.89% within 24h compared to free taxifolin. Moreover, GCS-Tax facilitated the production of short-chain fatty acid in mice and effectively alleviated DSS-induced colitis symptoms, including weight loss, bloody stools, and colonic tissue damage. Additionally, GCS-Tax significantly suppressed proinflammatory factors such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and lipopolysaccharide (LPS), while elevating anti-inflammatory interleukin-10 (IL-10) level in mice serum. Furthermore, it restored intestinal mucosal barrier function by upregulating the expression of Mucin 2, Occludin, and zonula occludens-1 (ZO-1), reducing Beclin 1 expression, and exhibited hepatoprotective effects by enhancing total antioxidant capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities. High-throughput sequencing analysis revealed that GCS-Tax improved intestinal flora diversity, reducing inflammation-related Bacterium 1 and Staphylococcus, while promoting the abundance of beneficial bacteria like Lachnospiraceae.

Optimizing Neuroprotective Nano-structured Lipid Carriers for Transdermal Delivery through Artificial Neural Network.

Dementia associated with Alzheimer's disease (AD) is a neurological disorder. AD is a progressive neurodegenerative condition that predominantly impacts the elderly population, although it can also manifest in younger people through the impairment of cognitive functions, such as memory, cognition, and behaviour. Donepezil HCl and Memantine HCl are encapsulated in Nanostructured Lipid Carriers (NLCs) to prolong systemic circulation and minimize the systemic side effects. This work explores the use of data mining tools to optimize the formulation of NLCs comprising of Donepezil HCl and Memantine HCl for transdermal drug delivery. Neuroprotective drugs and excipients are utilized for protecting the nervous system against damage or degeneration. The NLCs were formulated using a high-speed homogenization technique followed by ultrasonication. NLCs were optimized using Box Behnken Design (BBD) in Design Expert Software and artificial neural network (ANN) in IBM SPSS statistics. The independent variables included the ratio of solid lipid to liquid lipid, the percentage of surfactant, and the revolutions per minute (RPM) of the high-speed homogenizer. The NLCs that were formulated had a mean particle size ranging from 67.0±0.45 to 142.4±0.52nm. Both drugs have a %EE range over 75%, and Zeta potential was determined to be - 26±0.36mV. CryoSEM was used to do the structural study. The permeation study showed the prolonged release of the formulation. The results indicate that NLCs have the potential to be a carrier for transporting medications to deeper layers of the skin and reaching systemic circulation, making them a suitable formulation for the management of Dementia. Both ANN and BBD techniques are effective tools for systematically developing and optimizing NLC formulation.

Ultrasound-triggered drug release in vivo from antibubble-loaded macrophages.

Nanoparticles have proven to be attractive carriers in therapeutic drug delivery since they can encapsulate, protect and stabilize a plethora of different drugs, thereby improving therapeutic efficacy and reducing side effects. However, specific targeting of drug-loaded nanoparticles to the tissue of interest and a timely and spatially controlled release of drugs on demand still represent a challenge. Recently, gas-filled microparticles, so-called antibubbles, have been developed which can efficiently encapsulate liquid drug droplets. Here, we show that antibubbles are efficiently taken up by macrophages in vitro and are stably maintained for more than 48h without compromising antibubble integrity and macrophage viability. We show that application of diagnostic ultrasound induces the disintegration of both antibubbles and carrier cells while not affecting non-loaded macrophages. Using 4-hydroxytamoxifen as a model drug, we show ultrasound-mediated drug release upon adoptive transfer of antibubble-loaded macrophages in mice. Together with the ability of macrophages to accumulate in inflamed tissues, antibubble-loaded macrophages represent an attractive tool for targeted delivery of drugs and its ultrasound-mediated spatial and temporal drug release, highlighting the therapeutic perspective of this strategy.

Unveiling Spanlastics as a Novel Carrier for Drug Delivery: A Review.

Innovative colloidal preparations that can alter the pharmacological properties of drugs have been made possible by the advancement of nanotechnology. Recent advances in the sciences of the nanoscale have led to the creation of new methods for treating illnesses. Developments in nanotechnology may lessen the side effects of medicine by using effective and regulated drug delivery methods. A promising drug delivery vehicle is spanlastics, an elastic nanovesicle that can transport a variety of drug compounds. Spanlastics have expanded the growing interest in many types of administrative pathways. Using this special type of vesicular carriers, medications intended for topical, nasal, ocular, and trans-ungual treatments are delivered to specific areas. Their elastic and malleable structure allows them to fit into skin pores, making them ideal for transdermal distribution. Spanlastic is composed of non-ionic surfactants or combinations of surfactants. Numerous studies have demonstrated how spanlastics significantly improve, drug bioavailability, therapeutic effectiveness, and reduce medication toxicity. The several vesicular systems, composition and structure of spanlastics, benefits of spanlastics over alternative drug delivery methods, and the process of drug penetration via skin are all summarized in this paper. Additionally, it provides an overview of the many medications that may be treated using spanlastic vesicles. The primary benefits of these formulations were associated with their surface properties, as a variety of proteins might be linked to the look. For instance, procedure assessment and gold nanoparticles were employed as biomarkers for different biomolecules, which included tumor label detection. Anticipate further advancements in the customization and combining of spanlastic vesicles with appropriate zeta potential to transport therapeutic compounds to specific areas for enhanced disease treatment.

A correlation of polymorphic G-quadruplex formation in vitro and in the lysosomes of live cancer cells.

Guanine-rich oligonucleotides (GROs) can fold into G-quadruplex (G4) structures. The diverse roles of G4 structures, particularly as targets for drug design, anticancer agents, and drug delivery systems, highlight their critical significance in cancer research. However, the formation of G4 structures is highly dependent on the specific nucleotide sequences and the number of G-tracts within each GRO. In vitro studies using circular dichroism (CD), nuclear magnetic resonance (NMR), and polyacrylamide gel electrophoresis (PAGE) demonstrated that GROs with fewer than four G-tracts can form intermolecular G4 structures in K+ solution at 37°C. In fluorescence lifetime imaging microscopy study, intermolecular parallel G4 structures, formed by single-stranded GROs containing three G-tracts with three guanines each, were observed to be detectable in the lysosomes of live CL1-0 cancer cells. In contrast, a mutated sequence with only two G-tracts was rarely detected in the lysosomes of CL1-0 cancer cells, highlighting its incapability of forming intermolecular parallel G4s. Furthermore, polymorphic G4 formation in vitro and in-cell studies revealed a potential correlation. Our findings demonstrate that exogenous GROs can be introduced to explore the structural dynamics of G4 formation in live cancer cells, as well as their potential as anticancer agents and drug delivery carriers targeting lysosomes.

Stearic acid-capped mesoporous silica microparticles as novel needle-like-structured drug delivery carriers.

Mesoporous silica are widely utilised as drug carriers due to their large pore volume and surface area, which facilitate effective loading. Additionally, they can be used to enhance drugs stability and protect against enzymatic degradation due to their silica framework. However, without the addition of a capping material, the loaded cargo may be prematurely released before reaching the target site. This work reports the functionalisation of a commercially available silica microparticle (SYLOID XDP 3050) with stearic acid at various stearic acid loading concentrations (20-120% w/w). Scanning electron microscopy (SEM) analysis revealed that the pores were capped with stearic acid, with the filling ratio increasing proportionally to the loading concentration. Notably, needle-like structures appeared when the stearic acid amount exceeded 80% w/w, surpassing the calculated theoretical maximum pore filling ratio (64.32%). The molecular interactions were highlighted using Fourier-transform infrared spectroscopy (FTIR), as the intensity of the CH3 increased with increased stearic acid loading concentrations. The needle-structures phenomenon was corroborated by 3D confocal imaging. It utilised the autofluorescence properties of stearic acid to demonstrate its presence within the carrier, with fluorescence intensity increasing alongside the stearic acid concentration. Differential scanning calorimetry (DSC) indicated the crystalline nature of these needle structures, which was further confirmed by X-ray diffraction (XRD) analysis, validating the crystallisation of the stearic acid needles. Moreover, nitrogen porosimetry was employed to assess the pore volume and surface area, where the formulation containing 120% stearic acid exhibited the lowest pore volume (0.59cc). This value was smaller than unloaded SYLOID (2.1cc), indicating near-complete filling of the carrier. This newly developed SYLOID-stearic acid carrier will now be used to enhance formulation development as a platform to enhance protein oral drug delivery.

Melanoma extracellular vesicles membrane coated nanoparticles as targeted delivery carriers for tumor and lungs.

Targeting is the most challenging problem to solve for drug delivery systems. Despite the use of targeting units such as antibodies, peptides and proteins to increase their penetration in tumors the amount of therapeutics that reach the target is very small, even with the use of nanoparticles (NPs). Nature has solved the selectivity problem using a combination of proteins and lipids that are exposed on the cell membranes and are able to recognize specific tissues as demonstrated by cancer metastasis. Extracellular vesicles (EVs) have a similar ability in target only certain organs or to return to their original cells, showing home behavior. Here we report a strategy inspired by nature, using a combination of NPs and the targeting cell membranes of EVs. We implement the EV membranes, extracted by the EVs produced by melanoma B16-BL6 cells, as a coating of organosilica porous particles with the aim of targeting tumors and lung metastasis, while avoiding systemic effects and accumulation of the NPs in undesired organs. The tissue-specific fingerprint provided by the EVs-derived membranes from melanoma cells provides preferential uptake into the tumor and selective targeting of lungs. The ability of the EVs hybrid systems to behave as the natural EVs was demonstrated in vitro and in vivo in two different tumor models. As a proof of concept, the loading and release of doxorubicin, was investigated and its accumulation demonstrated in the expected tissues.

Encapsulation of individual mammalian cells as a cell-based drug delivery carrier for lung cancer treatment.

Cell-based delivery holds great promise for advancing cell therapy, but it often faces challenges such as low cell survival rates and immunological rejection during cell injection and circulation. In this study, we develop an alternative approach aimed at engineering cell membranes to produce encapsulated individual mammalian (EIM) cells. The encapsulation shell was formed by catalyzing the reaction of H2O2 with hyaluronic acid-dopamine (HA-DA) on the cell surface using horseradish peroxidase (HRP) enzymes. This protective shell not only protects live mammalian cells from physical stress but also from biological assaults. The individual cell encapsulation system enables the loading of cells with chemotherapy drugs, enhancing their targeting ability towards tumor sites and resulting in over 5.1-fold cell enrichment at metastatic tumors, thereby improving tumor-killing efficacy and reducing metastasis. Overall, the individual cell encapsulation system demonstrates potential for targeted drug delivery to the lungs in the treatment of lung cancer by reducing side effects and enhancing treatment outcomes.

Gold nanocomposites in colorectal cancer therapy: characterization, selective cytotoxicity, and migration inhibition.

The third most prevalent type of cancer in the world, colorectal cancer, poses a significant treatment challenge due to the nonspecific distribution, low efficacy, and high systemic toxicity associated with chemotherapy. To overcome these limitations, a targeted drug delivery system with a high cytotoxicity against cancer cells while maintaining a minimal systemic side effects represents a promising therapeutic approach. Therefore, the aim of this study was to develop an efficient gold nanocarrier for the targeted delivery of the anticancer agent everolimus to Caco-2 cells. A novel gold nanocomposite (EV-β-CD-HA-Chi-AuNCs) functionalized with a targeting ligand (hyaluronic acid), a permeation enhancement excipient (chitosan), and an anticancer inclusive compound consisting of beta-cyclodextrin and everolimus was proposed and prepared via Turkevich method. Characterization was performed with a UV spectrometer, FTIR, Zetasizer, and HRTEM. Its drug release profile was also evaluated in media with three different pH values. Cytotoxicity and biocompatibility studies were performed on a colorectal cancer cell line (Caco-2) and a normal fibroblast line (MRC-5), respectively, via xCELLigence real-time cellular analysis (RTCA) technology. The inhibitory effect on migration was also further tested via the xCELLigence RTCA technique and a scratch assay. Characterization studies revealed the successful formation of EV-β-CD-HA-Chi-AuNCs with a size and charge which are suitable for the use as targeted drug delivery carrier. In the cytotoxic study, the EV-β-CD-HA-Chi-AuNCs showed a lower IC50 (16 ± 1 µg/ml) than the pure drug (25 ± 3 µg/ml) toward a colorectal cell line (Caco-2). In the biocompatibility study, the EV-β-CD-HA-Chi-AuNCs have minimal toxicity, while the pure drug has severe toxicity toward healthy fibroblasts (MRC-5) despite its low concentration. In the cell migration study, the EV-β-CD-HA-Chi-AuNCs also showed a greater inhibitory effect than the pure drug. Compared with the pure drug, the EV-β-CD-HA-Chi-AuNCs exhibit an excellent selective cytotoxicity between cancerous colorectal Caco-2 cells and healthy MRC-5 cells, making it a potential carrier to carry the drug to the cancerous site while maintaining its low toxicity to the surrounding environment. In addition, an increase in the cytotoxic activity of the EV-β-CD-HA-Chi-AuNCs toward cancerous colorectal Caco-2 cells was also observed, which can potentially improve the treatment of colorectal cancer.

Antitumor Research Based on Drug Delivery Carriers: Reversing the Polarization of Tumor-Associated Macrophages.

The development of malignant tumors is a complex process that involves the tumor microenvironment (TME). An immunosuppressive TME presents significant challenges to current cancer therapies, serving as a key mechanism through which tumor cells evade immune detection and play a crucial role in tumor progression and metastasis. This impedes the optimal effectiveness of immunotherapeutic approaches, including cytokines, immune checkpoint inhibitors, and cancer vaccines. Tumor-associated macrophages (TAMs), a major component of tumor-infiltrating immune cells, exhibit dual functionalities: M1-like TAMs suppress tumorigenesis, while M2-like TAMs promote tumor growth and metastasis. Consequently, the development of various nanocarriers aimed at polarizing M2-like TAMs to M1-like phenotypes through distinct mechanisms has emerged as a promising therapeutic strategy to inhibit tumor immune escape and enhance antitumor responses. This Review covers the origin and types of TAMs, common pathways regulating macrophage polarization, the role of TAMs in tumor progression, and therapeutic strategies targeting TAMs, aiming to provide a comprehensive understanding and guidance for future research and clinical applications.

Effects of hydrophobic drug incorporation on cubosome-cell membrane model interactions

Abstract The impact of incorporating drug molecules into lipid carriers needs to be examined when investigating the interactions between carriers and cell membranes. In this work, we investigate the effects of loading of the drug, hydrocortisone, on the interactions of monoolein cubosomes with POPC cell membrane models (liposomes). Through the examination of the cubic structure and membrane, we elucidate the influence of the drug loading on the interaction. While the incorporation of the hydrocortisone did not alter the duration and kinetics of the cubic to lamellar phase transition, the membrane property analysis using Laurdan fluorescence probes showed slower kinetics in the drug loaded cubosomes. This implies that the rate of lipid exchange between carriers and cell membranes was suppressed in the presence of drug molecules. Such implication is important to consider when designing cubosomes as drug delivery carriers as it can affect factors such as their in-vivo performance and drug uptake.

Antarctic Krill Protein Amyloid Fibrils as a Novel Iron Carrier for the Improvement of Iron Deficiency.

Iron fortification with food supplements remains the primary dietary strategy for improving iron deficiency anemia (IDA). This study used Antarctic krill protein for fibrillar design to form an Antarctic krill protein amyloid fibril (AKAF). The results indicated that peptides generated by proteolysis were a prerequisite for fibril assembly, forming elongated fibril structures and cross-linking upon heating. During this process, hydrogen bonds were rearranged, forming ordered β-sheet conformations (49.36 ± 0.21%); π-π stacking interactions among aromatic residues contributed to fibril formation. Further studies showed that AKAF effectively maintained iron in a bioavailable state and exhibited a high binding capacity (60.67 ± 0.69%). Moreover, the AKAF-iron complex markedly ameliorated hematological abnormalities in IDA mice, enhanced iron storage in the liver and spleen, and positively influenced the expression of iron homeostasis genes. This complex was also effective in alleviating gastric inflammatory responses induced by IDA. Overall, AKAF holds promise as an efficient iron delivery carrier.

Psyllium: A Nutraceutical and Functional Ingredient in Foods.

Psyllium is an excellent natural source of soluble and insoluble dietary fiber. It has been used as a nutraceutical and functional ingredient in foods. Many efforts have been made to understand and improve its physicochemical, biological, and functional properties to promote its food applications. This manuscript reviews and discusses the current knowledge of psyllium, focusing on its health benefits, utilizations as a functional additive in foods and hydrogel delivery carrier, approaches to modify its molecular and chemical structures, nonfood utilizations, and potential side effects and toxicity. Perspectives on future research and development of psyllium are also provided. This review may serve as a scientific foundation for improved food application of psyllium to enhance human health and food quality.

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.

Emerging trends in designing polysaccharide based mucoadhesive network hydrogels as versatile platforms for innovative delivery of therapeutic agents: A review.

The rapid progress in polymer science has designed innovative materials for biomedical applications. In the case of drug design, for each new therapeutic agent, a drug delivery system (DDS) is required to improve its pharmacokinetic and pharmacodynamic parameters. Therefore, significant research has been carried out to develop drug delivery (DD) carriers for these new therapeutic agents. Hydrogels have been explored as potential candidates to prepare controlled drug delivery (CDD) systems to address the challenges related to the performance of the conventional DD formulations. Mucoadhesive drug delivery system (MUCO-DDS) is a specialized form of CDD system, facilitating site-specific DD, protecting the drug from first pass metabolism and enhancing its overall bioavailability. The present article provides a comprehensive discussion of the synthesis, properties and applications of polysaccharide-derived MUCO-DDS. Different natural polymer-derived MUCO-DDS including chitosan, alginate, pectin, xanthan gum, psyllium, gelatin, cellulose, hyaluronic acid, guar gum, sterculia gum and tragacanth gum have been reported. Herein, these DDS were elaborately discussed along with their applications and future-prospective. These DDS are classified on the basis of drug administration (nasal, ocular, vagina/rectal & buccal DDS) and drug distribution (reservoir and monolithic polymer matrix). Factors contributing to modifications of properties of MUCO-DDS were also demonstrated along with different stages and theories of mucoadhesion. Polysaccharides exhibit properties such as biocompatibility, biodegradability, and flexibility, making them ideal for CDD applications. MUCO-DDS demonstrates several significant advantages. Moreover, the article bridges theoretical insights with practical applications and future research prospects, ensuring its relevance for advancements in the concerned field. This review serves as a comprehensive resource, addressing gaps in previous literature and paving the way for innovations in MUCO-DDS, through a comparative analysis of the advantages, limitations, and modifications of natural polymers. In conclusion, this review gives an overview of the current developments in the field of mucoadhesive DD systems and also gives insights into the future perspectives. The MUCOAD of DDS could be modulated by the inclusion of various natural and synthetic components in hydrogels. Future directions for the researchers are underway to integrate nanotechnology with mucoadhesive systems to create hybrid platforms. Overall, by addressing current limitations and leveraging emerging technologies, these systems can revolutionize drug delivery for a wide range of therapeutic applications.

Atomized Neutrophil Membrane-coated MOF Nanoparticles for Direct Delivery of Dexamethasone for Severe Pneumonia.

Dexamethasone has proven life-saving in severe acute respiratory syndrome (SARS) and COVID-19 cases. However, its systemic administration is accompanied by serious side effects. Inhalation delivery of dexamethasone (Dex) faces challenges such as low lung deposition, brief residence in the respiratory tract, and the pulmonary mucus barrier, limiting its clinical use. Neutrophil cell membrane-derived nanovesicles, with their ability to specifically target hyper-activated immune cells and excellent mucus permeability, emerge as a promising carrier for pulmonary inhalation therapy. We designed a novel UiO66 metal-organic framework nanoparticle loaded with Dex and coated with neutrophil cell membranes (UiO66-Dex@NMP) for targeted therapy of severe pneumonia. This was achieved by loading Dex into UiO66 pores and subsequently coating with neutrophil membranes for functionalization. Drug release experiments revealed UiO66-Dex@NMP to exhibit favorable sustained-release properties. Additionally, UiO66-Dex@NMP demonstrated excellent targeting capabilities both in vitro and in vivo. In a mouse model of lipopolysaccharide (LPS)-induced pneumonia, UiO66-Dex@NMP significantly reduced lung inflammation compared to both the control model and Dex administered via inhalation. Histopathological analysis further confirmed UiO66-Dex@NMP's ability to alleviate lung tissue damage. UiO66-Dex@NMP represents a novel and safe inhaled delivery carrier for Dex, offering valuable insights into the clinical management of respiratory diseases, including severe pneumonia.

An effective cell-penetrating peptide-based loading method to extracellular vesicles and enhancement in cellular delivery of drugs.

Extracellular vesicles (EVs) have been demonstrated to own the advantages in evading phagocytosis, crossing biological barriers, and possessing excellent biocompatibility and intrinsic stability. Based on these characteristics, EVs have been used as effective therapeutic carriers for drug delivery, but the low drug loading capacity greatly limits further applications. Herein, we developed a drug loading method based on cell-penetrating peptide (CPP) to enhance the encapsulation of therapeutic reagents in EVs, and EVs-based drug delivery system achieved higher killing efficacy to tumor cells. Urinary EVs and chemotherapy reagent doxorubicin (DOX) were used as model. It is easy to conjugate CPP with DOX (CPP-DOX) through the linker N-succinimidyl 3-maleimidopropionate (SMP). CPP-DOX was incubated with EVs under a mild condition, promoting the encapsulation of DOX into EV cavities. CPP-DOX-EVs showed strong anticancer ability since EVs delivery facilitated the uptake by cancer cells. EVs loading of CPP-DOX exhibited higher drug loading efficiency at 37.18%, presenting about 2.5 times increase in efficiency over EVs loading of DOX through passive incubation. Easy operation and controllable condition further reinforce the advantages compared with other loading methods. CPP-based drug loading method provides an effective strategy for EVs-based drug delivery system.

SMILE-Derived Corneal Stromal Lenticule: Experimental Study as a Corneal Repair Material and Drug Carrier.

A detailed study of the physicochemical properties of SMILE-derived lenticules and evaluation of their drug delivery after loading with silver nanoparticles (AgNPs). The lenticules were decellularized and modified with crosslinking concentrations of 0.01 (0.01E/L), 0.05 (0.05E/L), and 0.25 (0.25E/L) mmol N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) per mg lenticule at 5:1 carbodiimide/N-hydroxysuccinimide (EDC/NHS) ratios. The degree of swelling, light transmittance, biomechanical properties, and stability of the non-crosslinked decellularized lenticules (DLs), 0.01E/L, 0.05E/L, and 0.25E/L were measured and characterized using Fourier transform infrared spectroscopy and transmission electron microscopy with non-crosslinked non-decellularized lenticules as controls. DLs, 0.01E/L, 0.05E/L, and 0.25E/L were soaked in AgNPs for 24 hours, and the concentration of the drug released was measured. There was no significant difference in the degree of swelling between the groups (P > 0.05). The light transmittance of the lenticules did not change after decellularization and crosslinking and decreased after loading with AgNPs. Non-decellularized lenticules biodegraded within 108 to 120 hours, and the other groups biodegraded within 96 to 108 hours in vitro. The 0.01E/L had the highest tensile strength. The absorption peak intensity ratio of the amide I band and the amide II band decreased, and the arrangement of collagen fibers was more compact in crosslinked decellularized lenticules. The 0.01E/L had the highest cumulative drug release (3.4 ± 0.91 μg). Crosslinking decellularization improved the biomechanical properties and resistance to water absorption of lenticules, increased covalent bonds between collagen fibers, and improved drug delivery. Crosslinked decellularized lenticules can be used as a new corneal patch material and drug delivery carrier for drug AgNPs.