High Loading Efficiency Research Articles

Nanocarriers Made of Natural Fatty Acids: Modulation of Their Release Profiles through Photo‐Crosslinking

AbstractNatural fatty acids are attractive carrier materials for drug delivery, but their rapid dissolution and degradation in vivo calls for new strategies to enhance their stability. Here we report a simple and versatile method capable of photo‐crosslinking carriers made of natural fatty acids for drug delivery under controlled release. By optimizing the crosslinking density, the nanoscale carriers show a high drug loading efficiency, together with a stable network structure for minimal degradation in a body fluid mimic. Fluorescence microscopy analysis also reveals the exceptional intracellular stability of the crosslinked network, resulting in negligible cytotoxicity toward A549 cells up to 24 h when loaded with a potent anticancer drug. We further extend this strategy to microscale carriers fabricated using electrospray. Upon photo‐crosslinking, the carriers show a retarded release of nerve growth factor, resulting in slower neurite outgrowth from dorsal root ganglion. This work holds promise for addressing the efficacy and safety issues critical to nanomedicine and related applications.

Designing of amiloride loaded citrate functionalized amorphous silica nanoparticles to investigate its genotoxic and cytotoxic potential

In the present work, silica-based nanocarrier for the anticancer drug, amiloride have been synthesized and characterized using various physicochemical techniques. The aim of this work emphasis on investigating the physicochemical properties and cytotoxic effects of citrate-functionalized amiloride loaded silica nanoparticles. Silica nanoparticles synthesis was carried out via condensation reaction, then coated by tris sodium citrate, followed by their functionalization using amiloride through EDC-NHS reaction. SEM and HR-XRD analysis indicated the formation of amorphous spherical silica nanoparticles. The existence of citrate coating was evident from FT-IR and TGA results, which were supported by DLS and zeta potential studies. The formation of amiloride conjugated citrate coated silica nanoparticles (SiNPs-Cit@Ami) was confirmed by the DLS, Zeta potential and UV-Visible spectroscopy. Size of SiNPs-Cit@Ami nanoparticles was found to be around 80nm using TEM. Additionally, these nanoparticles showed high loading efficiency and time-dependent release of amiloride. DNA binding studies were examined using UV–Visible, Fluorescence spectroscopic and Competitive fluorescence studies. The results indicate that SiNPs-Cit@Ami bind to Ct-DNA via minor groove binding mode. Furthermore, the cytotoxic effect of SiNPs-Cit@Ami on HepG2 cell lines was found to be higher than amiloride alone. Our findings suggest that SiNPs-Cit@Ami can be employed as a promising candidate for cancer mitigation.

Nanocarriers Made of Natural Fatty Acids: Modulation of Their Release Profiles through Photo-Crosslinking.

Natural fatty acids are attractive carrier materials for drug delivery, but their rapid dissolution and degradation in vivo calls for new strategies to enhance their stability. Here we report a simple and versatile method capable of photo-crosslinking carriers made of natural fatty acids for drug delivery under controlled release. By optimizing the crosslinking density, the nanoscale carriers show a high drug loading efficiency, together with a stable network structure for minimal degradation in a body fluid mimic. Fluorescence microscopy analysis also reveals the exceptional intracellular stability of the crosslinked network, resulting in negligible cytotoxicity toward A549 cells up to 24 h when loaded with a potent anticancer drug. We further extend this strategy to microscale carriers fabricated using electrospray. Upon photo-crosslinking, the carriers show a retarded release of nerve growth factor, resulting in slower neurite outgrowth from dorsal root ganglion. This work holds promise for addressing the efficacy and safety issues critical to nanomedicine and related applications.

Supramolecular Assembly‐Enabled Transdermal Therapy of Hypertrophic Scarring Through Concurrent Ferroptosis‐Apoptosis

AbstractHypertrophic scar (HS) remains a major challenge for clinicians due to unsatisfactory therapeutic performance. Although inducing apoptosis of HS fibroblasts (HSFs) has proved to be an effective nonsurgical treatment strategy, potential chemotherapy resistance to apoptosis of HSFs makes the development of new and efficient strategies highly demanding. Herein, a ferroptosis‐apoptosis combined therapeutic strategy for the treatment of HS is developed through supramolecular self‐assembly between cucurbit[7]uril (CB[7]) and two bioactive agents, dihydroartemisinin (DHA) and gold nanoclusters (AuNCs). The resulting self‐assembled supramolecular nanoparticles, named CAD NPs, showed high guest loading efficiency and prominent pH‐responsive degradability in the acidic lysosomes of HSFs. Importantly, both DHA and AuNCs act synergistically to generate excessive reactive oxygen species and lipid peroxidation, leading to mitochondrial damage, and ultimately inducing concurrent ferroptosis and apoptosis on HSFs. Upon further loading into hydrogel microneedles to facilitate their transdermal delivery, these CAD NPs showed superior antiscar therapeutic effects in shortening the treatment span to 3 weeks and improving the HS appearance, as demonstrated at a rabbit ear model of HS. The present supramolecular assembly‐based ferroptosis‐apoptosis strategy provides an innovative guideline for efficiently treating HS as well as other diseases.

Dynamic characteristics and transmission efficiency of energy-harvesting shock absorber with low speed and heavy duty capacity

Traditional hydraulic shock absorbers commonly encounter challenges such as cavitation, oil leakage, and the management of energy dissipation. The proposed regenerative shock absorber, which utilizes a ball screw mechanism, offers advantages such as high efficiency and heavy load capacity. This paper focuses on the design, modeling, and testing of a mechatronic shock absorber. Virtual prototype simulation techniques are employed to investigate the dynamic behaviors of the shock absorber. The paper presents a systematic efficiency model of a shock absorber, which is based on the ball screw and gearbox mechanisms. The study comprehensively analyzes the effects of rotation speed, axial load, and structure parameters on transmission efficiency. The results demonstrate that a peak power of 38 W can be achieved with a damping force of only 340 N, and the recovery efficiency can reach up to 28%. The experimental test results validate the effectiveness and reliability of the proposed dynamic and efficiency models. The originality of this study lies in the development of a novel energy-harvesting shock absorber with a ball screw mechanism in series with a gearbox, which shows excellent energy recovery potential and transmission efficiency under low speed and high duty conditions.

Electrodeposition Decoration of Pd0 on F‐Co(OH)2 Nanoarrays with Intentionally Introduced Pd2+ Species for Efficient Electrocatalytic Hydrodechlorination of 2,4‐Dichlorophenol

AbstractDeveloping a Pd‐based catalyst possessing high efficiency and low mass loading remains a big obstacle for the large‐scale application of electrocatalytic hydrodechlorination (EHDC) of chlorophenols (CPs). Herein, high dispersion Pd nanoparticles imbedded in Pd2+ hydroxide species are decorated on the surface of F−Co(OH)2 nanowire arrays with a newly developed electrodeposition and hydrolysis coupled process. EHDC of 2,4‐dichlorophenol (2,4‐DCP) with the as‐obtained Pd/F−Co(OH)2/NF‐a exhibits superior performance than other control samples in this work and literature reports. A 100 % removal of 2,4‐DCP is accomplished within 120 min, featuring fast reaction kinetics (kobs=5.0×10−2 min−1) and mass activity (MA=22.2 min−1 g−1Pd). Mechanism investigation shows that the intentionally introduced Pd2+ sites play a pivotal role in the adsorption of 2,4‐DCP, while high dispersion of Pd facilitates the generation of active H*, thus promoting the catalytic performance. This work presents a valuable example for designing high‐performance Pd‐based EHDC catalysts by composition tuning.

Inhibitory effect of RGD peptide hydrogel on inflammation and angiogenesis in vitro.

Inflammatory reaction and neovascularization are crucial physiological processes that occur during postoperative wound healing. However, excessive inflammatory response and uncontrolled angiogenesis lead to scar formation, which severely limits the success rate of glaucoma filtration surgery. Peptide hydrogels were well-established to possess good biocompatibility, inherent biodegradability, extracellular matrix analog property, and high drug loading efficiency. Herein, we examined the potential of Arg-Gly-Asp (RGD) peptide hydrogel to inhibit inflammation and angiogenesis in vitro experiments. RGD peptide hydrogel exhibited significant inhibitory effects on the inflammatory response by ELISA and western blot and considerable prohibitive effects on neovascularization via inhibiting the proliferation and migration of vascular endothelial cells. In this study, we found a novel biomaterial, RGD peptide hydrogel, which has a certain anti-cell proliferation and anti-scarring effect in vitro experiments.

Hepatic stellate cell-targeted chemo-gene therapy for liver fibrosis using fluorinated peptide-lipid hybrid nanoparticles

Exploring precise and effective treatments for liver fibrosis is urgent. The effective therapy for liver fibrosis depends on the specific delivery of antifibrotic drugs to activated hepatic stellate cells (aHSCs). However, this is a challenging task due to pathological barriers, primarily caused by collagen deposition. This study developed vitamin A-functionalized fluorinated peptide/lipid hybrid nanoparticles to co-deliver sorafenib and siRNA against HSP47 (SF-siHSP47@VFPL NPs). This nanoparticle formulation offers significant advantages due to its fluorine‑fluorine and electrostatic interactions, allowing for high SF and siHSP47 loading efficiency and sustained drug release. Importantly, in vitro cell uptake and in vivo biodistribution revealed that VA functionalization significantly improved aHSC-targeted delivery efficiency by engaging retinol-binding protein receptors on HSCs. Furthermore, it dramatically reduced extracellular matrix deposition, as evidenced by diminished levels of liver fibrosis-associated genes (HSP47, TIMP-1, and collagen I), promoting collagen breakdown and preventing collagen production, thus overcoming drug delivery barriers. Thus, SF-siHSP47@VFPL NPs demonstrated optimal antifibrotic effects by triggering apoptosis and ferroptosis in aHSCs. In liver fibrosis mouse models, SF-siHSP47@VFPL NPs remodeled the pathological environment and restored liver functionality through a marked reduction in serum liver transferases, hydroxyproline content, collagen deposition, and α-SMA and CD31 expression in liver tissue, resulting in alleviated liver fibrosis. Consequently, SF-siHSP47@VFPL NPs showed significant potential for HSC-targeted, chemo-gene therapy in the treatment of liver fibrosis.

Optimization of Truck–Cargo Matching for the LTL Logistics Hub Based on Three-Dimensional Pallet Loading

This study investigates the truck–cargo matching problem in less-than-truckload (LTL) logistics hubs, focusing on optimizing the three-dimensional loading of goods onto standardized pallets and assigning these loaded pallets to a fleet of heterogeneous vehicles. A two-stage hybrid heuristic algorithm is proposed to solve this complex logistics challenge. In the first stage, a tree search algorithm based on residual space is developed to determine the optimal layout for the 3D loading of cargo onto pallets. In the second stage, a heuristic online truck–cargo matching algorithm is introduced to allocate loaded pallets to trucks while optimizing the number of trucks used and minimizing transportation costs. The algorithm operates within a rolling time horizon, allowing it to dynamically handle real-time order arrivals and time window constraints. Numerical experiments demonstrate that the proposed method achieves high pallet loading efficiency (close to 90%), near-optimal truck utilization (nearly 95%), and significant cost reductions, making it a practical solution for real-world LTL logistics operations.

Thiacloprid-silica nano-delivery system enhances toxicity against Aphis gossypii and improves non-target biosafety

Nanotechnology aligns with the requirements of sustainable development of agriculture, and nano-pesticides offer a promising approach to controlling agricultural pests and increasing productivity. Non-target predators also play a crucial role in pest controls and enhancing the efficacy of pesticide on target organisms. Reducing the toxicity of pesticides to non-target organisms is key to of coordinating chemical control and biological control methods. Therefore, it is essential to assess the toxicity of nano-pesticides on non-target predators. In this study, a carbon dots-doped mesoporous silica nano-delivery system (Thi@CD-MSN) was successfully developed using CD-MSN as carrier material and thiacloprid (Thi) as a model pesticide. The results demonstrated that the synthesized Thi@CD-MSN exhibited a relatively high loading efficiency (33.58%). Laboratory bioassay experiments revealed that Thi@CD-MSN demonstrated effective insecticidal activity (LC50 = 21.67 mg/L) in controlling Aphis gossypii Glover. Besides, the acute toxicity of Thi@CD-MSN on Chrysoperla pallens larvae was significantly lower than that of Thi, as was its toxicity to 4T1 cells. These findings suggest that CD-MSN can serve as an ecological safety carrier for pesticide delivery, improving the effective utilization of Thi while reducing the risks to non-target predators. These results are essential for comprehending the effects of nano-pesticides on non-target predators, providing informative data for implementing biological and chemical control strategies. It strengthens the safety evaluation of nano-pesticides.

Doxorubicin-loaded methoxy-intercalated kaolinite as a repackaging of doxorubicin for an enhanced breast cancer treatment: in vitro and in vivo investigation

Doxorubicin is one of the most common wide-spectrum chemotherapeutics. However, its efficacy is limited due to off-target accumulation and selectivity issues. In this study, we compared the anti-cancer effect and biocompatibility of KaoliniteMeOH-Dox, a doxorubicin repackaging, to doxorubicin monotherapy. The formulation was extensively tested using transmission electron microscopy, dynamic light scattering, zeta potential, Fourier transform infrared, x-ray diffraction, and in vitro drug release. The MTT assay measured MCF-7 cell growth inhibition in vitro. In vivo testing involved 20 naïve mice and 40 Ehrlich solid tumor-inoculated mice. The tumor size was monitored for 18 days. In all experimental groups, tumor and cardiac tissues were evaluated for cytotoxicity and genotoxicity by addressing oxidative stress, histopathology, and comet assay. We found that kaoliniteMeOH-Dox has many advantages in terms of size, charge, shape, high loading efficiency (90.16%), and pH-dependent release. The MTT assay showed that the formulation outperformed doxorubicin in growth inhibition and selectivity. In vivo, research showed that kaoliniteMeOH-Dox suppressed tumors by 86.075% compared to 60.379% for free doxorubicin. Histological analysis showed that kaoliniteMeOH-Dox reduced tumor size, metastasis, and carcinogenic oxidative stress and inflammation in mice without harming naive mice. Based on the obtained data, the kaoliniteMeOH-Dox formulation holds promise for breast cancer treatment and warrants further investigation.

Metal-Organic Nanomaterials for Tumor Metabolic Blockade and Image to Increase Tumor Therapy.

The abnormal energy metabolism level of a tumor reduces the efficiency of chemotherapy. Metal-organic nanomaterials (MONs) with high drug loading efficiency, easy processes of synthesis, and controlled drug release have shown great potential in metabolic blocking and enhancement of tumor therapy. These metal-organic nanomedicines have been reported to modulate glycolysis or oxidative phosphorylation to provide monotherapy or combined therapies in tumorous treatments. In addition, the encapsulation or coordination of fluorescent dyes into MONs endowed them with the imaging ability of tumor metabolism. Herein, this Perspective summarizes the progress of MONs as therapeutic agents or imaging probes for application during tumor metabolic blocking or imaging, providing solid inspiration for biomedical applications of effective biomaterials. In addition, the current drawbacks of MONs for further biological applications in the future were discussed, giving stimulation of innovation and development in biomedical applications of MONs.

Pesticide delivery microcapsule based on maleic anhydride‐functionalized cellulose nanocrystals‐stabilized pickering emulsion

AbstractThe efficient use of pesticides is conducive to the harmonious coexistence of humans and nature, and pesticide transport carriers can enhance the utilization value of pesticides. However, design flaws in many pesticide carriers have resulted in numerous environmental and toxicity problems. Therefore, this paper proposed a method for synthesizing pesticide microcapsules using Pickering emulsion templates stabilized by maleic anhydride‐functionalized cellulose nanocrystals‐g‐poly (methyl methacrylate) (MACNCs‐g‐MMA), viz., simple radical polymerization of maleic anhydride‐functionalized cellulose nanocrystals with methyl methacrylate in Pickering emulsion. The structure and morphology of microcapsules were characterized via the FT‐IR, XRD, TG‐DTG, and SEM techniques. The imidacloprid‐loaded MACNCs‐g‐MMA (IMI@MACNCs‐g‐MMA) presented a high encapsulation efficiency (~94.13%) and drug loading efficiency (~24.00%). The release behavior was affected by temperature, viz., higher temperature promoted the release of IMI. Regarding the spread and retention on the leaf surface, the IMI@MACNCs‐g‐MMA demonstrated significant advantages over commercial IMI water‐dispersible granules (CG) (36.9° vs. 104.9° for contact angle, 14.3 vs. 30.0 mg cm−2 for retention). This study provides a promising pesticide formula for sustainable agriculture.

Design and development of DSPE-PEG2000/DPPC disk-like micelles for targeted delivery of icariin phytochemical in pulmonary fibrosis

Icariin (ICA)-loaded DSPE-PEG2000/DPPC disk-like micelles were synthesized utilizing the thin film hydration method to enhance the solubility and delivery of ICA to the lungs. The micellar formulation significantly improved the water solubility of ICA. This was attributed to the high encapsulation efficiency (95 %) and drug loading capacity (12 %) of the DSPE-PEG2000/DPPC micelles. Comprehensive characterization using Fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Particle size analysis through dynamic light scattering (DLS) and transmission electron microscopy (TEM) demonstrated the formation of stable micelles with an average particle size around 10 nm.In vitro aerosolization studies using the next-generation impactor (NGI) revealed that the fine particle fraction was 63.5 ± 4 %, which means that over 60 % of the aerosolized ICA/DSPE-PEG2000/DPPC micelles were capable of reaching and targeting the deep lung alveoli, indicating their potential efficacy for pulmonary delivery. Cytotoxicity assessments via the MTT assay showed IC50 values of ICA-loaded DSPE-PEG2000/DPPC micelles were 117 ± 8 μg/mL, 29 ± 3 μg/mL, and 21 ± 1 μg/mL at 24, 48, and 72 h, respectively, highlighting the time-dependent cytotoxic effects of the ICA-loaded micelles on A549 cells. However, the IC50 values of free ICA were > 500 μg/mL, 252 ± 3 μg/mL, and 109 ± 2 μg/mL, respectively at three different time points. That indicated that ICA-loaded nano micelles enhanced the cytotoxicity of ICA. Furthermore, the cellular uptake of the nano micelles by A549 cells was visualized and confirmed using EVOS fluorescence imaging and flow cytometry techniques. In addition, RAW 264.7 M2 polarization studies indicated ICA loaded DSPE-PEG2000/DPPC micelles have potential for treating pulmonary fibrosis.These findings suggest that DSPE-PEG2000/DPPC micelles significantly enhance the solubility and delivery of ICA, presenting a promising nanocarrier system for targeted pulmonary fibrosis therapy.

Co-freezing localized CRISPR-Cas12a system enables rapid and sensitive nucleic acid analysis

Rapid and sensitive nucleic acid detection is vital in disease diagnosis and therapeutic assessment. Herein, we propose a co-freezing localized CRISPR-Cas12a (CL-Cas12a) strategy for sensitive nucleic acid detection. The CL-Cas12a was obtained through a 15-minute co-freezing process, allowing the Cas12a/crRNA complex and hairpin reporter confined on the AuNPs surface with high load efficiency, for rapid sensing of nucleic acid with superior performance to other localized Cas12a strategies. This CL-Cas12a based platform could quantitatively detect targets down to 98 aM in 30 min with excellent specificity. Furthermore, the CL-Cas12a successful applied to detect human papillomavirus infection and human lung cancer-associated single-nucleotide mutations. We also achieved powerful signal amplification for imaging Survivin mRNA in living cells. These findings highlight the potential of CL-Cas12a as an effective tool for nucleic acid diagnostics and disease monitoring.Graphical abstract

Aluminum phthalocyanine tetrasulfonate conjugated to surface-modified Iron oxide nanoparticles as a magnetic targeting platform for photodynamic therapy of Ehrlich tumor-bearing mice

BackgroundPhotodynamic therapy (PDT) is a targeted treatment option for cancers that are non-responding to ordinary anticancer therapies. It involves activating a photosensitizer with a light source of a specific wavelength to destroy targeted cells and their surrounding vasculature. Aluminum phthalocyanine tetra sulfonate (AlPcS4) has gained attention as a second-generation photosensitizer for its strong absorption in the red-light region. AlPcS4 can be conjugated to magnetic iron oxide nanoparticles (IONs) to provide targeted drug delivery to the tumor cells while reducing its undesired effect on healthy tissues in other body parts. MethodsMagnetic glutamine functionalized iron oxide nanocomposites loaded with AlPcS4 (IONs-NH2-AlPcS4) were synthesized via the co-precipitation method. The conjugate (IONs-NH2-AlPcS4) was characterized by TEM, Zeta potential, DLS, FTIR, and UV–VIS absorption spectroscopy. Furthermore, its photodynamic activity was investigated using albino mice with induced Ehrlich solid tumors. ResultsAlPcS4 was successfully conjugated to IONs-NH2 with a high loading efficiency of 54±2%. The synthesized conjugate exhibited a spherical shape, with 7 ± 2 nm particle size. The In vivo experiment revealed that the albino mice with induced Ehrlich solid tumor that were treated by combined PDT and magnetic targeting conjugate exhibited significant tumor regression and notably higher levels of necrotic tissue compared to the animals in other groups. ConclusionPDT mediated by magnetic targeting significantly inhibited tumor growth with minimal adverse effects, indicating its great potential as a promising strategy for solid cancer treatment.

Charge regulated pH/NIR dual responsive nanoplatforms centered on cuproptosis for enhanced cancer theranostics

Multifunctional nanoplatforms capable of simultaneously executing multimodal therapy and imaging functions are of great potentials for cancer theranostics. We present an elegantly designed, easy-to-fabricate poly(acrylic acid)/mesoporous calcium phosphate/mesoporous copper phosphate nanosphere (PAA/mCaP/mCuP NS) with outstanding pH/NIR-sensitive multimodal-synergic anti-tumor effects. Optimal porous PAA NS scaffolds were prepared at room temperature by balancing the intra-PAA polymer and polymer-solvents Lennard-Jones potentials in a water:isopropyl alcohol (IPA) mix-solvent. Subsequent sponging of Ca2+ and Cu2+, and adsorption of PO43− to the PAA template were achieved through exquisite electrostatic interactions among ions and the ionizable PAA side-chain in an aqueous environment. This forms the basis for the tumor microenvironment pH-triggered release of Cu2+ to induce cuproptosis, as well as the photothermal effect originating from CuP, while Ca2+ can enhance the nanoplatform's biocompatibility and can damage mitochondria when overloaded. Lastly, PAA/mCaP/mCuP NSs still exhibit high drug loading efficiency for doxorubicin (DOX), enabling chemotherapy. Satisfactory anti-tumor effects of these modalities, along with their synergistic effects, were verified both in vitro and in vivo, with the NSs demonstrating good biodegradation in the latter. The fabricated NS itself holds great promise as an anti-tumor nanomedicine, and the thorough mechanical insights into NS formation may inspire the design of next-generation multifunctional nanoplatforms.

Novel CD44-Targeted Albumin Nanoparticles: An Innovative Approach to Improve Breast Cancer Treatment.

This study introduces novel CD44-targeted and redox-responsive nanoparticles (FNPs), proposed as doxorubicin (DOX) delivery devices for breast cancer. A cationized and redox-responsive Human Serum Albumin derivative was synthesized by conjugating Human Serum Albumin with cystamine moieties and then ionically complexing it with HA. The suitability of FNPs for cancer therapy was assessed through physicochemical measurements of size distribution (mean diameter of 240 nm), shape, and zeta potential (15.4 mV). Nanoparticles possessed high DOX loading efficiency (90%) and were able to trigger the drug release under redox conditions of the tumor environment (55% release after 2 h incubation). The use of the carrier increased the cytotoxic effect of DOX by targeting the CD44 protein. It was shown that, upon loading, the cytotoxic effect of DOX was enhanced in relation to CD44 protein expression in both 2D and 3D models. DOX@FNPs significantly decrease cellular metabolism by reducing both oxygen consumption and extracellular acidification rates. Moreover, they decrease the expression of proteins involved in the oxidative phosphorylation pathway, consequently reducing cellular viability and motility, as well as breast cancer stem cells and spheroid formation, compared to free DOX. This new formulation could become pioneering in reducing chemoresistance phenomena and increasing the specificity of DOX in breast cancer patients.

Acrylic Acid Modified Poly-ethylene Glycol Microparticles for Affinity-Based release of Insulin-Like Growth Factor-1 in Neural Applications.

Sustained release of bioactive molecules via affinity-based interactions presents a promising approach for controlled delivery of growth factors. Insulin-like growth factor-1 (IGF-1) has gained increased attention due to its ability to promote axonal growth in the central nervous system. In this work, we aimed to evaluate the effect of IGF-1 delivery from polyethylene-glycol diacrylate (PEG-DA) microparticles using affinity-based sustained release on neurons. We developed PEG-DA-based microparticles with varying levels of acrylic acid (AA) as a comonomer to tune their overall charge. The particles were synthesized via precipitation polymerization under UV light, yielding microparticles (MPs) with a relatively low polydispersity index. IGF-1 was incubated with the PEG-DA particles overnight, and formulations with a higher AA content resulted in higher loading efficiency and slower release rates over 4 weeks, suggesting the presence of binding interactions between the positively charged IGF-1 and negatively charged particles containing AA. The released IGF-1 was tested in dorsal root ganglion (DRG) neurite outgrowth assay and found to retain its biological activity for up to two weeks after encapsulation. Furthermore, the trophic effect of IGF-1 was tested with stem cell-derived V2a interneurons and found to have a synergistic effect when combined with neurotrophin-3 (NT3). To assess the potential of a combinatorial approach, IGF-1-releasing MPs were encapsulated within a hyaluronic acid (HA) hydrogel and showed promise as a dual delivery system. Overall, the PEG-DA MPs developed herein deliver bioactive IGF-1 for a period of weeks and hold potential to enable axonal growth of injured neurons via sustained release.

Hyaluronic acid/chitosan microcapsules capped with hollow CuS nanoparticles for NIR/pH dual-responsive drug release

Hollow natural polysaccharide microcapsules have broad applications in drug delivery field due to their excellent biocompatibility and drug loading efficiency. In this paper, pH/near-infrared (NIR) dual-responsive microcapsules composed of hyaluronic acid (HA), chitosan (CS) and hollow CuS (HA/CS/HA@CuS) had been fabricated via a layer-by-layer (LbL) approach. The negative charge, rough surface and hollow structure of microcapsules are very favorable for loading positively charged DOX. As a result, hollow microcapsules display a high drug loading efficiency of 91.15 %. The variation in the degree of amino ionization at different pH values leads to the changes in the electrostatic force between CS/HA multilayers, resulting in the structural change in microcapsules. Therefore, microcapsules exhibit significant pH-responsive drug release properties. In addition, hollow CuS nanoparticles with excellent photothermal conversion ability are capped on the multilayer surface, enabling microcapsules to exhibit excellent NIR-responsive drug delivery properties. Overall, hyaluronic acid/chitosan-based hollow microcapsules with notable pH/NIR dual-responsiveness have been prepared, which can be used as a potential drug carrier for controlled drug delivery and photothermal chemical combination therapy.