Sustained Drug Release System Research Articles

Boundary-lubricated biomaterials with drug delivery for osteoarthritis treatment

AbstractThe good lubrication ability of articular cartilage holds significant importance in our daily lives. Osteoarthritis (OA), the most prevalent degenerative joint disease, causes cartilage damage, increased friction, and inflammation. However, the current clinical treatments for OA exhibit some defects. Recently, the sustained drug release systems with lubricating function have attracted considerable attention for treating OA. This review introduces the lubrication mechanism of cartilage, focusing particularly on the boundary lubrication mechanism. The research progress of boundary-lubricated biomaterials with drug delivery, including microcarriers, hydrogels, and nanoparticles in the treatment of OA by improving inter-articular lubrication and relieving inflammation is discussed and summarized. The efficacy and challenges of boundary-lubricated biomaterials with drug delivery in the treatment of OA are summarized, and the prospects are also discussed.

Photo-crosslinkable polyester microneedles as sustained drug release systems toward hypertrophic scar treatment

Burn injuries can result in a significant inflammatory response, often leading to hypertrophic scarring (HTS). Local drug therapies e.g. corticoid injections are advised to treat HTS, although they are invasive, operator-dependent, extremely painful and do not permit extended drug release. Polymer-based microneedle (MN) arrays can offer a viable alternative to standard care, while allowing for direct, painless dermal drug delivery with tailorable drug release profile. In the current study, we synthesized photo-crosslinkable, acrylate-endcapped urethane-based poly(ε-caprolactone) (AUP-PCL) toward the fabrication of MNs. Physico-chemical characterization (1H-NMR, evaluation of swelling, gel fraction) of the developed polymer was performed and confirmed successful acrylation of PCL-diol. Subsequently, AUP-PCL, and commercially available PCL-based microneedle arrays were fabricated for comparative evaluation of the constructs. Hydrocortisone was chosen as model drug. To enhance the drug release efficiency of the MNs, Brij®35, a nonionic surfactant was exploited. The thermal properties of the MNs were evaluated via differential scanning calorimetry. Compression testing of the arrays confirmed that the MNs stay intact upon applying a load of 7 N, which correlates to the standard dermal insertion force of MNs. The drug release profile of the arrays was evaluated, suggesting that the developed PCL arrays can offer efficient drug delivery for up to two days, while the AUP-PCL arrays can provide a release up to three weeks. Finally, the insertion of MN arrays into skin samples was performed, followed by histological analysis demonstrating the AUP-PCL MNs outperforming the PCL arrays upon providing pyramidical-shaped perforations through the epidermal layer of the skin.

Potent inhibition of MMP-9 by a novel sustained-release platform attenuates left ventricular remodeling following myocardial infarction

Sustained drug-release systems prolong the retention of therapeutic drugs within target tissues to alleviate the need for repeated drug administration. Two major caveats of the current systems are that the release rate and the timing cannot be predicted or fine-tuned because they rely on uncontrolled environmental conditions and that the system must be redesigned for each drug and treatment regime because the drug is bound via interactions that are specific to its structure and composition. We present a controlled and universal sustained drug-release system, which comprises minute spherical particles in which a therapeutic protein is affinity-bound to alginate sulfate (AlgS) through one or more short heparin-binding peptide (HBP) sequence repeats. Employing post-myocardial infarction (MI) heart remodeling as a case study, we show that the release of C9—a matrix metalloproteinase-9 (MMP-9) inhibitor protein that we easily bound to AlgS by adding one, two, or three HBP repeats to its sequence—can be directly controlled by modifying the number of HBP repeats. In an in vivo study, we directly injected AlgS particles, which were bound to C9 through three HBP repeats, into the left ventricular myocardium of mice following MI. We found that the particles substantially reduced post-MI remodeling, attesting to the sustained, local release of the drug within the tissue. As the number of HBP repeats controls the rate of drug release from the AlgS particles, and since C9 can be easily replaced with almost any protein, our tunable sustained-release system can readily accommodate a wide range of protein-based treatments.

MiRNA320a Inhibitor-Loaded PLGA-PLL-PEG Nanoparticles Contribute to Bone Regeneration in Trauma-Induced Osteonecrosis Model of the Femoral Head.

This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin-eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.

Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis

Exosomes (Exos) secreted by adipose-derived stem cells (ADSCs) have shown potential in alleviating osteoarthritis (OA). Previous studies indicated that infrapatellar fat pad (IPFP) derived stem cells (IPFSCs) may be more suitable for the treatment of OA than subcutaneous adipose tissue (ScAT) derived stem cells (ScASCs). However, it remains unclear which type of Exos offers superior therapeutic benefit for OA. This study first compared the differences between Exos derived from IPFP stem cells (ExosIPFP) and ScAT stem cells (ExosScAT) in OA treatment. Results suggested that ExosIPFP significantly inhibit the degradation of cartilage extracellular matrix (ECM) than ExosScAT, following this, the differences in microRNA (miRNA) expression between the two types of Exos using small RNA sequencing were performed. Subsequently, miR-99 b-3p was chosen and over-expressed in ExosScAT (ExosScAT−99b−3p), both in vivo and in vitro experiments demonstrated its efficacy in inhibiting the expression of ADAMTS4, promoting the repair of the ECM in OA. Finally, microfluidic technology was performed to fabricate a hyaluronan-based hydrogel microparticles (HMPs) for encapsulating Exos (HMPs@exos), the injectability, sustained release of Exos and long-term therapeutic effect on OA were validated. In summary, these results suggest miR-99 b-3p regulates the degradation of cartilage ECM by targeting ADAMTS4, the upregulation of miR-99 b-3p in ExosScAT would enable them to exhibit comparable or even superior effectiveness to ExosIPFP for OA treatment, making it a promising approach for OA treatment. Considering the abundant resources of ScAT and the limited availability of IPFP, ScAT harvested through liposuction could be genetically engineered to yield Exos for OA treatment. Furthermore, the encapsulation of Exos in HMPs provides an injectable sustained local drug release system, which could potentially enhance the efficacy of Exos and hold potential as future therapeutic strategies.

A short review on the applicability and use of cubosomes as nanocarriers.

Cubosomes are nanostructured lipid-based particles that have gained significant attention in the field of drug delivery and nanomedicine. These unique structures consist of a three-dimensional cubic lattice formed by the self-assembly of lipid molecules. The lipids used to construct cubosomes are typically nonionic surfactants, such as monoolein, which possess both hydrophilic and hydrophobic regions, allowing them to form stable, water-dispersible nanoparticles. One of the key advantages of cubosomes is their ability to encapsulate and deliver hydrophobic as well as hydrophilic drugs. The hydrophobic regions of the lipid bilayers provide an ideal environment for incorporating lipophilic drugs, while the hydrophilic regions can encapsulate water-soluble drugs. This versatility makes cubosomes suitable for delivering a wide range of therapeutic agents, including small molecules, proteins, peptides, and nucleic acids. The unique structure of cubosomes also offers stability and controlled release benefits. The lipid bilayers provide a protective barrier, shielding the encapsulated drugs from degradation and improving their stability. Moreover, the cubic lattice arrangement enables the modulation of drug release kinetics by varying the lipid composition and surface modifications. This allows for the development of sustained or triggered drug release systems, enhancing therapeutic efficacy and reducing side effects. Furthermore, cubosomes can be easily modified with targeting ligands or surface modifications to achieve site-specific drug delivery, enhancing therapeutic selectivity and reducing off-target effects. In conclusion, cubosomes offer a versatile and promising platform for the delivery of therapeutic agents. In this manuscript, we will highlight some of these applications.

Synergistic Sustained Drug-Release System Based on Immobilized Rhamnus frangula L. Phytoextract into Layered Double Hydroxide Covered by Biocompatible Hydrogel.

This work focuses on the synergetic effect obtained by immobilization of Rhamnus frangula L. (RfL) phytoextract in layered double hydroxides (LDHs) matrixes and their subsequent encapsulation into biocompatible hydrogels (HG). In this respect, the LDHs were used as hosts for the immobilization of the phytoextract by a reconstruction method, after which the LDHsRfL were embedded into biocompatible hydrogel (HG) matrixes, based on polyethylene glycol diacrylate (PEGDA), by a radical polymerization reaction. The resulted biocompatible hydrogel composites were characterized by modern methods, while the swelling and rheology measurements revealed that the HG composites steadily improved as the content of RfL phytoextract immobilized on LDHs (LDHsRfL) increased. The following in vitro sustained release of the RfL phytoextract was highlighted by measurements at pH 6.8, in which case the composite HGs with LDHsRfL presented an improved release behavior over the LDHsRfL, thus, underlining the synergistic effect of PEGDA network and LDH particles on the slow-release behavior. The kinetic models used in the RfL release from composite HGs clearly indicate that the release is diffusion controlled in all the cases. The final composite HGs described here may find applications in the pharmaceutical field as devices for the controlled release of drugs.

Preparation of amylopectin and chitosan based polyurethanes for sustained drug release studies

Herein, we engineered first-time chitosan (CS) and amylopectin (AMP) blends-based polyurethanes (PUs) for sustained drug release systems. Polycaprolactone diol (PCL) and isophorone diisocyanate (IPDI) were used for the preparation of prepolymer, then blends of CS and AMP were reacted as a chain extender for the development of polyurethanes. Ciprofloxacin drug (5%) was loaded in the polymer and in vitro release of the drug was studied up to 240 hours. The synthesis of PUs was monitored using Fourier-transformed infrared (FTIR) and proton nuclear magnetic resonance (1H NMR) spectroscopic techniques. The molecular weights of the prepared polymers were measured using gel permeation chromatography (GPC). The thermal degradation behavior of prepared samples was recorded using thermal gravimetric analysis (TGA). Polyurethane prepared with equimolar blends of CS and AMP showed minimum release of the drug as compared to pristine CS and AMP based PUs.

Structural complexity and physical mechanism of self-assembled lipid as nanocarriers: A review

Lipids such as glyceryl monooleate, phosphatidylcholine, and monoglyceride (CITREM) possess an amphipathic property that allows them to self-assemble into a complex internal structure when interacting with an aqueous solution. Since amphiphilic molecules possess hydrophilic heads and lipophilic tails, hydrophobic effects cause the spontaneous activity of the molecular rearrangement. The self-organization of the molecules often results in the phases of lipid polymorphism, for example microemulsion, inverse bicontinuous cubic (Q2), discontinuous hexagonal (H2), and micellar cubic (I2) Fd3m. Interestingly, these lamellar and non-lamellar phases have been applied in the development of nanocarriers for drug delivery due to their ability to provide a sustained drug release system, better drug bioavailability, and improved overall treatment. However, the attention that they are receiving from their application is not comparable to our understanding of the mechanisms involved in their synthesis. Elucidation of the spontaneous process helps in predicting and tuning the internal structure of an amphiphilic molecule to suit its application. Therefore, this review discusses the formation of lipid polymorphism from the thermodynamic point of view, critical packing parameter, and modified stalk theory.

Scientometric Research on Trend Analysis of Nano-Based Sustained Drug Release Systems for Wound Healing.

Nanomaterials, such as the nanoparticle (NP), nanomicelle, nanoscaffold, and nano-hydrogel, have been researched as nanocarriers for drug delivery more and more recently. Nano-based drug sustained release systems (NDSRSs) have been used in many medical fields, especially wound healing. However, as we know, no scientometric analysis has been seen on applying NDSRSs in wound healing, which could be of great importance to the relevant researchers. This study collected publications from 1999 to 2022 related to NDSRSs in wound healing from the Web of Science Core Collection (WOSCC) database. We employed scientometric methods to comprehensively analyze the dataset from different perspectives using CiteSpace, VOSviewer, and Bibliometrix. The results indicated that China published the most significant number of documents in the last two decades, Islamic Azad Univ was the most productive institution, and Jayakumar, R was the most influential author. Regarding the analysis of keywords, trend topics indicate that "antibacterial", "chitosan (CS)", "scaffold", "hydrogel", "silver nanoparticle", and "growth factors (GFs)" are the hot topics in recent years. We anticipate that our work will provide a comprehensive overview of research in this field and help scholars better understand the research hotspots and frontiers in this area, thus inspiring further explorations in the future.

Low glutaminase and glycolysis correlate with a high transdifferentiation efficiency in mouse cortex.

Both exogenous transcriptional factors and chemical-defined medium can transdifferentiate astrocytes into functional neurons. However, the regional preference for such transdifferentiation has not been fully studied. A previously reported 5C medium was infused into the mouse cortex and striatum to determine the regional preference for transdifferentiation from astrocytes to neurons. The numbers of NeuN+ GFAP+ EdU+ cells (intermediates) and NeuN+ EdU+ cells (end products) were determined by immunofluorescence to explore the regional preference of transdifferentiation. In addition, to optimize the delivery of the transdifferentiation medium, three key growth factors, insulin, bFGF and transferrin, were loaded onto chitosan nanoparticles, mixed with gelatin methacryloyl and tested in animals with motor cortex injury. A higher transdifferentiation efficiency was identified in the mouse cortex. Differences in cellular respiration and the balance between glutaminase (Gls) and glutamine synthetase were confirmed to be key regulators. In addition, the sustained drug release system induced transdifferentiation of cortex astrocytes both in vivo and in vitro, and partially facilitated the behaviour recovery of mice with motor cortex injury. We also applied this method in pigs and obtained consistent results. In summary, low Gls and glycolysis can be used to predict high transdifferentiation efficiency, which may be useful to identify better indications for the current transdifferentiation system. In addition, the current drug delivery system has the potential to treat diseases related to cortex injuries.

Characteristics of Mitomycin C-Loaded Peptide Hydrogel In Vitro and Antiscarring Effects in Rat Ocular Injury Model.

Purpose: To investigate the characteristics of sustained drug release systems established by an arginine-glycine-aspartic acid (RGD) peptide hydrogel and mitomycin C (MMC) in vitro, and verify their antiscar effects in rat ocular injury model. Methods: Low, medium, and high loading doses of MMC were added to 5 mL 0.25%, 0.5%, and 1% wt RGD peptide hydrogel, respectively, to prepare 9 ratios of MMC-RGD systems. Drug release characteristics of the systems in phosphate-buffered saline solution were investigated by plotting the drug release curves and fitting them with mathematical models in OriginPro8.0 software. Appropriate ratios of MMC-RGD systems were selected as treatment in rat ocular injury model. Scar formation was observed by Masson staining and immunohistochemical staining with alpha-smooth muscle actin (α-SMA) and fibronectin (FN). Results: Nine ratios of MMC-RGD systems could release drug slowly. The maximum drug release proportions of all systems were >80%, and the time to maximum release proportions statistically prolonged with the increase of drug loading. Fitting with mathematical models indicated that the mechanisms of drug release were mainly Fick diffusion at early stage and Anomalous Transport at later stage. Systems of 1% wt RGD hydrogel were evaluated in animal experiments, which could inhibit hyperplasia of collagen and expression of α-SMA and FN. Conclusions: The RGD peptide hydrogel could be used as the carrier of MMC to establish sustained drug release system, which could inhibit scar formation after rat's ocular injury.

Synergistic Occlusion of Doxorubicin and Hydrogels in CaCO3 Composites for Controlled Drug Release

Extensive exploration is required to deploy mineralization as a tool to develop low-cost yet efficient sustained drug release systems. Unlike previous studies which directly incorporated drug components in mineralized products, we propose an emerging approach to synthesizing drug-loaded CaCO3 composites, relying on the synergistic occlusion of the molecular solutions comprising both the alginate hydrogel matrices and the associated drug (doxorubicin) in the course of mineralization. Independent tools including a scanning electron microscope and adsorption isotherm were employed to characterize the lyophilized composites, which led to the conclusion that the anticancer drug doxorubicin (DOX) was uniformly dispersed in the hydrogel matrices as a molecular solution. The occlusion strategy led to CaCO3-based composites with high loads and sustained and pH-responsive release of DOX. Considering many drug molecules can form molecular solutions with polymeric components, we find that the synergistic occlusion can become a general approach to designing smart drug delivery systems.

Self-sealing chemistry of calcium/magnesium silicate on porous silicon nanoparticles for enhanced drug-loading and slowed drug-releasing

Calcium/Magnesium Silicate Self-Sealing Chemistry on Porous Silicon Nanoparticles is disclosed for Enhanced Drug-loading and Slowed Drug-releasing. • Ca 2+ /Mg 2+ -silicate-sealed porous silicon nanoparticle formulation is disclosed. • The nano-formulation showed an enhanced drug-loading efficiency and slowed the drug-release profiling. • The nano-formulation showed a prolonged degradation rate in biological media. Porous silicon nanoparticles (pSiNP) have gained much attention in the biomedical field due to their high biocompatibility, high drug loading efficiency, and easy surface modification. However, pSiNP are easily degraded in biological media, which is the limitation to applying to the sustained drug release system. In this study, we prepared a new pSiNP-based nano-formulation (Ca/Mg-pSiNP) using self-sealing chemistry of calcium ion (Ca 2+ ) and magnesium ion (Mg 2+ ), and characterized its drug release profiles. Ca/Mg-pSiNP could incorporate the drug with high loading efficiency, and its degradation rate was slowed compared with the pristine pSiNP or Ca-sealed/Mg-sealed pSiNP in biological media. This work offers a sustained released property in a long-term drug delivery system using pSiNP.

A pH-Sensitive Chitosan/Oxidized-Kappa-Carrageenan based Nano-Antibiotic for Sustained and Controlled Release of Amoxicillin

Nowadays antibiotic resistance is one of the most serious problems. Therefore, there is a need for sustained and controlled drug release systems for antibiotics. The aim of this study was to develop a nano-antibiotic system using biocompatible and antimicrobial polymers that are abundant in nature. Frequently used amoxicillin was chosen as the antibiotic. Before nanoparticle synthesis kappa-carrageenan was oxidized and 1.2% carboxyl, and 23.08% aldehyde groups were obtained, as confirmed by Fourier-transform infrared spectroscopy. A combination of polyelectrolyte complexation and ionic gelation was occurred in the nanoparticle synthesis. For the optimal temperature, CaCl2 concentration and polymer ratio of 37 °C, 1.5% and 6:1, respectively, the results of hydrodynamic size measurements indicated the size was 414.4 nm. Drug loading encapsulation was successful with an efficiency of 73.28%. Drug release was monitored for 95 h, and drug release was 93% and 85%, respectively, at pH 6.0 and pH 7.4. It is shown by the mathematical models that the drug release profile can be explained by the Higuchi and first-order models since R 2 values were higher than for the other models. As a result, it was observed that the obtained nano-antibiotic delivery system performed a long-term drug release of approximately 4 days in a pH-sensitive manner and would be a promising drug delivery system.

Preparation of poly (N-isopropylacrylamide)/polycaprolactone electrospun nanofibres as thermoresponsive drug delivery systems in wound dressing

A thermo-sensitive film composed of polycaprolactone and poly(N-isopropylacrylamide) was fabricated via electrospinning, with ketoconazole as the model drug. The morphology, elemental composition, and surface hydrophilicity of the nanofibres were characterized, and the results showed that nanofibres switched from a hydrophilic to a hydrophobic state as the temperature increased from 25 °C to 37 °C. The drug release profiles of the films suggested that sustained drug release behavior was achieved, and a lower temperature induced a faster delivery. Therefore, the prepared nanofibres could be highly applicable as wound dressings for on-demand and sustained drug release systems based on their temperature-responsive properties.

Synthesis of core-shell structure based on silica nanoparticles and methacrylic acid via RAFT method: An efficient pH-sensitive hydrogel for prolonging doxorubicin release

In recent years, much attention has been received on stimuli-responsive nanocarriers in nanomedicine. In this work, a pH-responsive core-shell system based on silica nanoparticles (SNPs) as core and methacrylic acid hydrogels as shell were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Methacrylic acid hydrogel through bulk and RAFT polymerization was developed as a model to compare with core-shell hydrogel. The synthesized nanocarriers were characterized by TGA, FT-IR, SEM, TEM, and DLS techniques. To investigate the synthesized core-shell nanoparticles as anticancer nanocarriers, Doxorubicin (DOX) was used as a model drug. In-vitro drug release manner at physiological barriers (pH 7.4) and cancer cell conditions (pH 4.8) illustrates a pH-controlled release for the nanocarriers over 15 days. The study of drug release kinetics reveals that the release mechanism of the carriers followed by the Gompertz model. In addition, the DOX-loaded nanocarriers have notable cytotoxicity against human breast MCF-7 cells with 0.7866 μM IC50 for core-shell nanocarrier. The obtained results showed that the prepared pH-responsive core-shell hydrogel has a high potential to be employed as a sustained pH-sensitive drug release system.

Injectable and Thermosensitive Liposomal Hydrogels for NIR-II Light-Triggered Photothermal-Chemo Therapy of Pancreatic Cancer.

An injectable hydrogel sustained drug release system could be a promising technique for in situ treatment. Herein, an injectable hydrogel was prepared for photothermal-chemo therapy of cancer based on the thermosensitive liposomal hydrogel (Lip-Gel). The Lip-Gel system was fabricated by encapsulation of the NIR-II photothermal agent (DPP-BTz) and chemotherapy drugs (GEM) in thermosensitive liposomes and then combined with hydrogel precursor solution. The hydrogel precursor was used as an injectable flowing solution at room temperature and transferred into a cross-linked gel structure at physiological temperature. After being injected into the tumor, DPP-BTz in the Lip-Gel system can generate heat under irradiation of 1064 nm laser, breaking the thermosensitive liposomes and releasing GEM to kill tumor cells. From the treatment results, the Lip-Gel system showed a significant antitumor effect through chemo-/photothermal therapy combination therapy triggered by the NIR-II laser. This work provides a useful scheme for the development of drug delivery and drug treatment directions for local cancer therapy.

Construction of a Drug Release Evaluation System: Application of Mitochondrial Respiration to Monitor Drug Release.

Efficient drug encapsulation and regulation of drug release are important factors for sustained drug release and application for release-controlled anti-cancer and anti-inflammatory drug delivery. In the present study, a direct evaluation system for drug-release from model carrier (e.g., alginate-gel beads) was examined using the mitochondrial oxygen consumption rate as an index. Alginate-gel beads were coated with the uncoupler SF6847 (SF beads) and used as a model microparticle-type drug. The real-time monitoring of SF6847 release from prepared alginate-gel beads was performed using the mitochondrial oxygen consumption rate. Release profiles of nonsteroidal anti-inflammatory drugs [NSAIDs, mefenamic acid (MEF) and diclofenac (DIC)] from alginate-gel beads as well as SF beads were investigated using the real time monitoring system. SF6847 release from alginate-gel beads was clearly detected using the rat liver mitochondrial oxygen consumption rate. The release features of MEF and DIC from alginate-gel beads were defined by the present trial monitoring system, and these NSAIDs exhibited different release profiles. The present drug monitoring system detected released drugs, and the release profile reflected the molecular properties of the test drugs. This system may be applied to the design and development of precise sustained drug release systems (e.g., anti-cancer and anti-inflammatory drugs).

Injectable chitosan hydrogel embedding modified halloysite nanotubes for bone tissue engineering

Low mechanical strength and untargeted osteoinduction of chitosan hydrogel limit its application for bone regeneration. This study aimed to develop an injectable chitosan hydrogel with enhanced mechanical strength and improved osteoinductivity for bone tissue engineering. For this purpose, chitosan-modified halloysite nanotubes (mHNTs) were synthesized first. Then, icariin as a bone inducer was loaded into mHNTs (IC@mHNTs), resulting in a sustained drug release system. Further, nanocomposite chitosan/mHNTs hydrogels were prepared by the sol-gel transition, leading to decreased gelation time and temperature and enhanced mechanical strength of the resulting scaffolds. The mesenchymal stem cells were encapsulated into the hydrogels, and in vitro viability assays showed scaffold biocompatibility. Moreover, embedded mHNTs or IC@mHNTs in the scaffold resulted in enhanced proliferation and bone differentiation of encapsulated cells. It was collectively demonstrated that the injectable in situ forming nanocomposite chitosan hydrogel loaded with IC@mHNTs is a promising candidate for bone regeneration.