Controlled Release Systems Research Articles

Degradable Self-Destructive Redox-Responsive System Based on Mesoporous Organosilica Nano-Vehicles for Smart Delivery of Fungicide

The development of stimuli-responsive controlled release formulations is a potential method of improving pesticide utilization efficiency and alleviating current pesticide-related environmental pollution. In this study, a self-destruction redox-responsive pesticide delivery system using biodegradable disulfide-bond-bridged mesoporous organosilica (DMON) nanoparticles as the porous carriers and coordination complexes of gallic acid (GA) and Fe(III) ions as the capping agents were established for controlling prochloraz (PRO) release. The GA-Fe(III) complexes deposited onto the surface of DMON nanoparticles could effectively improve the light stability of prochloraz. Due to the decomposition of GA-Fe(III) complexes, the nano-vehicles had excellent redox-responsive performance under the reducing environments generated by the fungus. The spreadability of PRO@DMON-GA-Fe(III) nanoparticles on the rice leaves was increased due to the hydrogen bonds between GA and rice leaves. Compared with prochloraz emulsifiable concentrate, PRO@DMON-GA-Fe(III) nanoparticles showed better fungicidal activity against Magnaporthe oryzae with a longer duration under the same concentration of prochloraz. More importantly, DMON-GA-Fe(III) nanocarriers did not observe obvious toxicity to the growth of rice seedlings. Considering non-toxic organic solvents and excellent antifungal activity, redox-responsive pesticide controlled release systems with self-destruction properties have great application prospects in the field of plant disease management.

Fabrication of a controlled-release delivery system for relieving sciatica nerve pain using an ultrasound-responsive microcapsule.

Lidocaine, a potent local anesthetic, is clinically used in nerve block and pain management. However, due to its short half-life, repeated administration is required. For this reason, here we designed and prepared a lidocaine-encapsulated polylactic acid-glycolic acid (Lidocaine@PLGA) microcapsule with ultrasound responsiveness to relieve the sciatica nerve pain. With a premixed membrane emulsification strategy, the fabricated lidocaine-embedded microcapsules possessed uniform particle size, good stability, injectability, and long-term sustained release both in vitro and in vivo. More importantly, Lidocaine@PLGA microcapsules had the function of ultrasonic responsive release, which made the drug release controllable with the effect of on-off administration. Our research showed that using ultrasound as a trigger switch could promote the rapid release of lidocaine from the microcapsules, achieving the dual effects of long-term sustained release and short-term ultrasound-triggered rapid release, which can enable the application of ultrasound-responsive Lidocaine@PLGA microcapsules to nerve root block and postoperative pain relief.

Miscibility of Poly(lactide-co-glycolide) in Supercritical fluids

In a polymer based drug delivery system, the polymer material surrounds the drug and delivers the substance to the desired target. Poly(lactide-co-glycolide) (PLGA) is the most widely used control-release system for many drugs with a short half-life, low stability, easy decomposition, and non-toxic side effects. Supercritical fluid (SCF) technology can be used to prepare or micronize drug-loaded particles without additional purification or cleaning procedures. In this work, the liquid–liquid phase transition of PLGA in several supercritical fluids, such as dimethyl ether (DME), CO2, chlorodifluoromethane (HCFC-22), and trifluoromethane (HFC-23), has been investigated. PLGA with a higher content of glycolide in the copolymer backbone shows upper critical solution temperature (UCST)-type phase behavior. Alternatively, in supercritical HCFC-22, lower critical solution temperature (LCST)-type phase behavior has been observed. The ratio of lactide to glycolide in the PLGA copolymer backbone majorly controls the phase behavior including the pressure–temperature (p-T), temperature-polymer weight fraction (T-w), pressure-density (p-ρ), and temperature-density (T-ρ) isopleths. The phase behaviors of PLGA in SCF CO2 and DME change from UCST- to LCST-type behavior with an increase in the lactide content. In contrast, PLGA in SCF HCFC-22 exhibits LCST-type phase behavior for all PLGA copolymers irrespective of the lactide content. Such phase behaviors are described well by the perturbed-chain statistical associating fluid theory (PC-SAFT) in a wide range of temperature (300–395 K) and pressure (3–310 MPa) with temperature-independent binary interaction parameters. In addition, significant differences have been observed in the solubility of PLGA in different SCFs; CO2 being the poorest solvent, and HCFC-22 being the best solvent.

Formulation and Evaluation of Flurbiprofen Topical Emulgels

Topical drug delivery has been used for centuries for the treatment of local skin disorders. Emulgel have emerged as one of the most interesting topical delivery system as it has dual control release system i.e. gel and emulsion. One side the topical applications of the drug offers the potential advantages of delivering the drug directly to the site of action and secondly delivering the drug for extended period of time at the effected site. Topical non-steroidal anti-inflammatory drug (NSIAD) formulations are designed to deliver therapeutic levels of the active ingredients to the inflamed tissue without elevating serum levels after application on the skin. This route is an attractive alternative to the oral administration of NSAIDS which is associated with high incidence of gastrointestinal tract (GIT) complications and other systemic toxic effects. Flurbiprofen is a potent non-steroidal anti-inflammatory agent usually well tolerated as compared to other NSAIDS product. It has analgesic and antipyretic properties. It is used in the treatment of rheumatic disorders such as ankylosing spondilities, oesteoarthritis and intraoperative miosis. It suffers from major GIT disturbances. The aim of the present study was to develop an emulgel formulation of flurbiprofen using water soluble polymer of hydroxy propyl methyl cellulose (HPMC K100M), carbopol 940, carbopol 941 and xanthan gum. Oleic acid and propylene glycol were used as permeation enhancers. The influence of the type of the gelling agent on the drug release from the prepared emulgel was investigated. The prepared emulgels were evaluated for their physical appearance, pH determination, viscosity, spreadability, extrudability, in-vitro drug release, ex-vivo drug release and stability. All the prepared emulgels showed acceptable physical properties, homogeneity, consistency, spreadability, viscosity and pH value. The emulgels were found to be stable with respect to physical appearance, pH, and rheological properties and drug content at all temperature and conditions for one month. Keywords: Emulgel, Topical drug delivery, Flurbiprofen, Carbopol, Hydroxy propyl methyl cellulose

Thermo-sensitive composite microspheres incorporating cellulose nanocrystals for regulated drug release kinetics

Thermo-sensitive composite microspheres (TPCP) were developed to achieve the on-demand release of drugs. The TPCP microspheres were synthesized using Oil-in-Water (O/W) emulsion evaporation technique and then impregnated with thermo-sensitive polyethylene glycol (PEG). The addition of cellulose nanocrystals (CNCs) significantly enhance thermal stability, crystallization ability, and surface hydrophilicity of TPCP microspheres due to heterogeneous nucleation effect and hydrogen bonding interaction, resulting in stable microsphere structure. The thermal degradation temperature (Tmax) increased by 13.8 °C, and the crystallinity improved by 20.9 % for 10 % TPCP. The thermo-sensitive composite microspheres showed the regulated cumulative release according to in vitro human physiological temperature changes. Besides, four release kinetics and possible release mechanism of TPCP microspheres were provided. Such thermo-responsive composite microspheres with control microsphere sizes and high encapsulation rate may have the potential to the development of on-demand and advanced controlled-release delivery systems.

Advanced Studies on Drug Delivery Systems: Characterization and Their Impact on Pharmaceutical and Medicinal Areas

This work shows some advanced studies in model pharmaceutical formulations that help to develop guidelines for the rational design of controlled release systems [...]

Preparation and Characterizations of Curcumin Protection and Delivery System Using Linear Dextrin

In this work, linear dextrins (LDs) with the fragment F-40 (DP = 31.44) were fabricated from waxy potato starch through pasteurization and enzymatic debranching by pullulanase and then separated and extracted by ethanol solutions with different concentrations. The LDs were used to encapsulate hydrophobic ligand curcumin to develop a controlled release system that would increase its flavor in food and functions in medicines. The physicochemical properties and the encapsulation mechanism of the inclusion complexes were investigated. It was found that the loading capability for curcumin, the encapsulation rate, and the yield of the complexes depended on the molecular weight of LD. The yield of the LD-Cur complex, its encapsulation rate, and loading of curcumin were 19.86%, 25.81%, and 29.52 μg/mg, respectively, while the yield of the F-40-Cur complex, its inclusion rate, and loading curcumin reached up to 75.98%, 29.97%, and 37.52 μg/mg, respectively. There were both hydrogen bonding and hydrophobic interactions between LD and curcumin, while hydrogen bonding interactions were predominant between F-40 and curcumin. Curcumin was presented in the complex in an amorphous form. The photothermal stability of curcumin increased after being complexed with LD and further enhanced significantly with F-40. The release of curcumin in the intestine was achieved much more effectively.

AIEgen-Enabled Multicolor Visualization for the Formation of Supramolecular Polymer Networks.

Extensive reports on the use of supramolecular polymer networks (SPNs) in self-healing materials, controlled release system and degradable products have led more researchers to tap their potential owing to the unique properties. Yet, the attendant efforts in the visualization through conventional luminescence methods during the formation of SPNs have been met with limited success. Herein, we designed a special type of SPNs prepared by PPMU polymer chains containing pyrene benzohydrazonate (PBHZ) molecules as AIEgens for the multicolor visualization with naked eyes. The complete detection of the formation process of the networks relied on the PBHZ molecules with aggregation-induced ratiometric emission (AIRE) effect, which enabled the fluorescence of the polymer networks transits from blue to cyan, and then to green with the increasing crosslinking degree derived from the hydrogen bonds between 2-ureido-4-pyrimidone (UPy) units of the polymer chains. Additionally, we certificated the stimuli-responsiveness of the obtained SPNs, and the fluorescence change, as well as observing the morphology transition. The AIEgen-enabled multicolor visualization of the formation of SPNs may provide better understanding of the details of the crosslinking interactions in the microstructural evolution, giving more inspiration for the multifunctional products based on SPNs.

Fabrication of a dual pH-responsive and photothermal microcapsule pesticide delivery system for controlled release of pesticides.

The development of stimulus-responsive and photothermally controlled-release microcapsule pesticide delivery systems is a promising solution to enhance the effective utilization and minimize the excessive use of pesticides in agriculture. In this study, an AVM@CS@TA-Fe microcapsule pesticide delivery system was developed using avermectin as the model drug, chitosan and tannic acid as the wall materials, and tannic acid-Fe complex layer as the photothermal agent. The optical microscope, scanning electron microscope, transmission electron microscope, and Fourier-transform infrared spectroscope were used to characterize the prepared microcapsule. The slow-release, UV-shielding, photothermal performance, and nematicidal activity of the microcapsule were systematically investigated. The results showed that the system exhibited excellent pH-responsive and photothermal-sensitive performances. In addition, the UV-shielding performance of the delivery system was improved. The photothermal conversion efficiency (η) of the system under the irradiation of near-infrared (NIR) light was determined to be 14.18%. Moreover, the nematicidal activities of the system against pine wood nematode and Aphelenchoides besseyi were greatly increased under the irradiation of light-emitting diode (LED) simulated sunlight. The release of the pesticide-active substances in such a pesticide delivery system could be effectively regulated with the irradiation of NIR light or LED-simulated sunlight. Thus, the developed pesticide delivery system may have broad application prospects in modern agriculture fields. © 2022 Society of Chemical Industry.

Developments on the Smart Hydrogel-Based Drug Delivery System for Oral Tumor Therapy.

At present, an oral tumor is usually treated by surgery combined with preoperative or postoperative radiotherapies and chemotherapies. However, traditional chemotherapies frequently result in substantial toxic side effects, including bone marrow suppression, malfunction of the liver and kidneys, and neurotoxicity. As a new local drug delivery system, the smart drug delivery system based on hydrogel can control drug release in time and space, and effectively alleviate or avoid these problems. Environmentally responsive hydrogels for smart drug delivery could be triggered by temperature, photoelectricity, enzyme, and pH. An overview of the most recent research on smart hydrogels and their controlled-release drug delivery systems for the treatment of oral cancer is given in this review. It is anticipated that the local drug release method and environment-responsive benefits of smart hydrogels will offer a novel technique for the low-toxicity and highly effective treatment of oral malignancy.

Applications of Metallic Nanoparticles in the Skin Cancer Treatment.

Skin cancer is one of leading cancers globally, divided into two major categories including melanoma and nonmelanoma. Skin cancer is a global concern with an increasing trend, hence novel therapies are essential. The local treatment strategies play a key role in skin cancer therapy. Nanoparticles (NPs) exert potential applications in medicine with huge advantages and have the ability to overcome common chemotherapy problems. Recently, NPs have been used in nanomedicine as promising drug delivery systems. They can enhance the solubility of poorly water-soluble drugs, improve pharmacokinetic properties, modify bioavailability, and reduce drug metabolism. The high-efficient, nontoxic, low-cost, and specific cancer therapy is a promising goal, which can be achieved by the development of nanotechnology. Metallic NPs (MNPs) can act as important platforms. MNPs development seeks to enhance the therapeutic efficiency of medicines through site specificity, prevention of multidrug resistance, and effective delivery of therapeutic factors. MNPs are used as potential arms in the case of cancer recognition, such as Magnetic Resonance Imaging (MRI) and colloidal mediators for magnetic hyperthermia of cancer. The applications of MNPs in the cancer treatment studies are mostly due to their potential to carry a large dose of drug, resulting in a high concentration of anticancer drugs at the target site. Therefore, off-target toxicity and suffering side effects caused by high concentration of the drug in other parts of the body are avoided. MNPs have been applied as drug carriers for the of improvement of skin cancer treatment and drug delivery. The development of MNPs improves the results of many cancer treatments. Different types of NPs, such as inorganic and organic NPs have been investigated in vitro and in vivo for the skin cancer therapy. MNPs advantages mostly include biodegradability, electrostatic charge, good biocompatibility, high drug payload, and low toxicity. However, the use of controlled-release systems stimulated by electromagnetic waves, temperature, pH, and light improves the accumulation in tumor tissues and improves therapeutic outcomes. This study (2019-2022) is aimed at reviewing applications of MNPs in the skin cancer therapy.

Analyzing and mapping the research status, hotspots, and frontiers of biological wound dressings: An in-depth data-driven assessment

Wound dressings can be applied over the wound sites to provide long-lasting wound management and improve wound healing. Biological wound dressings are superior to synthetic materials due to biodegradability and biocompatibility. These biomaterials have demonstrated huge potential in the field of wound dressings. Applying bibliometric analysis combined with results-based descriptions to characterize the research status, hotspots, and cutting-edge topics, this study is the first in-depth qualitative, quantitative, data-driven overview of biological wound dressings research in recent decades. Filtered data were used to construct co-citation, heatmaps, bi-clustering, strategy maps, and other analyses and visualization. The results show that research on biological wound dressings has progressed considerably in the last 5 years with extensive global collaboration. A clear knowledge base has been developed. Chitosan hydrogels, bacterial cellulose, active agents (silver nanoparticles, growth factors, curcumin, etc.), and electrospinning fibers stand out as research hotspots. The research frontiers include novel starting materials, precise and controlled release systems, and clinical and regenerative medicine applications. We interpreted an overview of the excavated topics and expected the findings here to provide a guide and inspire innovations for developing the next generation wound dressings.

Preparation of Transdermal Patch Containing Selenium Nanoparticles Loaded with Doxycycline and Evaluation of Skin Wound Healing in a Rat Model.

The present study aimed to prepare and evaluate a controlled-release system based on a chitosan scaffold containing selenium nanoparticles loaded with doxycycline. Its topical application in skin wound healing in rats was investigated. Therefore, 80 female rats were used and, after creating experimental skin defects on their back, were randomly divided into four equal groups: the control group without any therapeutic intervention; the second group received a chitosan transdermal patch (Ch); the third group received chitosan transdermal patch loaded with selenium nanoparticles (ChSeN), and the last group received chitosan transdermal patch containing selenium nanoparticle loaded by doxycycline (ChSeND). Morphological and structural characteristics of the synthesized patches were evaluated, and in addition to measuring the skin wound area on days 3, 7, and 21, a histopathological examination was performed. On the third day of the study, less hemorrhage and inflammation and more neo-vascularization were seen in the ChSeND group. Moreover, on day 7, less inflammation and collagen formation were recorded in the ChSeN and ChSeND groups than in the other groups. At the same time, more neo-vascularization and re-epithelialization were seen in the ChSeND group on days 7 and 21. In addition, on day 21 of the study, the most collagen formation was in this group. Examination of the wound area also showed that the lowest area belonged to the ChSeND group. The results showed that the simultaneous presence of selenium nanoparticles and doxycycline in the ChSeND group provided the best repair compared to the control, Ch and ChSeN groups.

Direct contact-mediated non-viral gene therapy using thermo-sensitive hydrogel-coated dressings

Nanotechnologies are being increasingly applied as systems for peptide and nucleic acid macromolecule drug delivery. However systemic targeting of these, or efficient topical and localized delivery remains an issue. A controlled release system that can be patterned and locally administered such as topically to accessible tissue (skin, eye, intestine) would therefore be transformative in realizing the potential of such strategies. We previously developed a technology termed GAG-binding enhanced transduction (GET) to efficiently deliver a variety of cargoes intracellularly, using GAG-binding peptides to mediate cell targeting, and cell penetrating peptides (CPPs) to promote uptake. Herein we demonstrate that the GET transfection system can be used with the moisturizing thermo-reversible hydrogel Pluronic-F127 (PF127) and methyl cellulose (MC) to mediate site specific and effective intracellular transduction and gene delivery through GET nanoparticles (NPs). We investigated hydrogel formulation and the temperature dependence of delivery, optimizing the delivery system. GET-NPs retain their activity to enhance gene transfer within our formulations, with uptake transferred to cells in direct contact with the therapy-laden hydrogel. By using Azowipe™ material in a bandage approach, we were able to show for the first-time localized gene transfer in vitro on cell monolayers. The ability to simply control localization of gene delivery on millimetre scales using contact-mediated transfer from moisture-providing thermo-reversible hydrogels will facilitate new drug delivery methods. Importantly our technology to site-specifically deliver the activity of novel nanotechnologies and gene therapeutics could be transformative for future regenerative medicine.

Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury

BackgroundTraumatic peripheral nerve injury (TPNI) is a major medical problem with no universally accepted pharmacologic treatment. We hypothesized that encapsulation of pro-angiogenic erythropoietin (EPO) in amphiphilic PLGA-PEG block copolymers could serve as a local controlled-release drug delivery system to enhance neurovascular regeneration after nerve injury.MethodsIn this study, we synthesized an EPO-PLGA-PEG block copolymer formulation. We characterized its physiochemical and release properties and examined its effects on functional recovery, neural regeneration, and blood vessel formation after sciatic nerve crush injury in mice.ResultsEPO-PLGA-PEG underwent solution-to-gel transition within the physiologically relevant temperature window and released stable EPO for up to 18 days. EPO-PLGA-PEG significantly enhanced sciatic function index (SFI), grip strength, and withdrawal reflex post-sciatic nerve crush injury. Furthermore, EPO-PLGA-PEG significantly increased blood vessel density, number of junctions, and myelinated nerve fibers after injury.ConclusionThis study provides promising preclinical evidence for using EPO-PLGA-PEG as a local controlled-release treatment to enhance functional outcomes and neurovascular regeneration in TPNI.

Translating controlled release systems from biomedicine to agriculture

Sustainable food production is a grand challenge facing the global economy. Traditional agricultural practice requires numerous interventions, such as application of nutrients and pesticides, of which only a fraction are utilized by the target crop plants. Controlled release systems (CRSs) designed for agriculture could improve targeting of agrochemicals, reducing costs and improving environmental sustainability. CRSs have been extensively used in biomedical applications to generate spatiotemporal release patterns of targeted compounds. Such systems protect encapsulant molecules from the external environment and off-target uptake, increasing their biodistribution and pharmacokinetic profiles. Advanced ‘smart’ release designs enable on-demand release in response to environmental cues, and theranostic systems combine sensing and release for real-time monitoring of therapeutic interventions. This review examines the history of biomedical CRSs, highlighting opportunities to translate biomedical designs to agricultural applications. Common encapsulants and targets of agricultural CRSs are discussed, as well as additional demands of these systems, such as need for high volume, low cost, environmentally friendly materials and manufacturing processes. Existing agricultural CRSs are reviewed, and opportunities in emerging systems, such as nanoparticle, ‘smart’ release, and theranostic formulations are highlighted. This review is designed to provide a guide to researchers in the biomedical controlled release field for translating their knowledge to agricultural applications, and to provide a brief introduction of biomedical CRSs to experts in soil ecology, microbiology, horticulture, and crop sciences.

Innovative therapeutic approach to chemical burns produced by vesicants; an experimental study

Vesicants are compounds that cause severe toxic effects on various tissues. Such chemical action causes tissue necrosis, with clinical expression of skin lesions with a burning character and characteristic blisters. Clinical toxic effects of cutaneous vesicles are correlated with the absorbed dose and exposure time. The goals of the study are to evaluate in vitro the skin toxicity produced by the vesicant chemical compound 2-chloroethyl-ethyl sulfide (CEES), to develop a complex antidote formula, and to optimize the therapeutic efficacy by inclusion in controlled release systems. The experimental protocol aims at the in vitro evaluation of the cytotoxicity of the vesicant compound CEES and of the optimized complex antidote, using the MTT cell viability test. Optimization of the complex antidote formula was achieved by developing and in vitro and in vivo testing of a fixed combination of active substances with anti-inflammatory and antioxidant effects, formulated as a solution with cutaneous administration. In vitro cytotoxicity tests on fibroblast cultures revealed the protective effect of the newly developed antidote solution, specifically a dose-related effect in the case of vesicant exposure.

Electrospun poly(l‐lactide‐co‐ε‐caprolactone)/gelatin core–shell nanofibers encapsulated with doxorubicin hydrochloride as a drug delivery system

AbstractAdvanced application of coaxial electrospinning nanofibers in controlled drug release systems has gathered much attention since they have had a tunable structure for tailored release of drugs, including various proteins, growth factors, antibacterial and anticancer agents. The composite polymer poly(l‐lactide‐co‐ε‐caprolactone) (PLCL) blended with gelatin (GE) was used as the shell material to electrospin core–shell nanofibers. Model drug doxorubicin hydrochloride (DOX) was encapsulated in the core layers. The morphology and core–shell structure were evaluated by SEM and TEM respectively. The existence of DOX in the inner part of DOX/PLCL/GE nanofibers could be proved by Fourier transform infrared spectroscopy results. The water contact angle test results indicated that DOX/PLCL/GE nanofibers all possess good hydrophilicity with water contact angles as low as 51.2°. The in vitro release results indicated that the DOX/PLCL/GE nanofibers showed a sustained release profile for 480 h. The fitting results showed that the release kinetics of DOX from nanofibers was consistent with a Ritger–Peppas model, presenting a typical Fickian diffusion mechanism. Overall, the DOX/PLCL/GE core–shell nanofibers showed regulable mechanical properties and could be used as a promising drug release system for drug sustained release and tissue engineering. © 2022 Society of Chemical Industry.

Sodium Alginate-Natural Microencapsulation Material of Polymeric Microparticles.

From the multitude of materials currently available on the market that can be used in the development of microparticles, sodium alginate has become one of the most studied natural anionic polymers that can be included in controlled-release pharmaceutical systems alongside other polymers due to its low cost, low toxicity, biocompatibility, biodegradability and gelatinous die-forming capacity in the presence of Ca2+ ions. In this review, we have shown that through coacervation, the particulate systems for the dispensing of drugs consisting of natural polymers are nontoxic, allowing the repeated administration of medicinal substances and the protection of better the medicinal substances from degradation, which can increase the capture capacity of the drug and extend its release from the pharmaceutical form.

Titanium surface polyethylene glycol hydrogel and gentamicin-loaded cross-linked starch microspheres release system for anti-infective drugs

Objective To design and construct a hydrogel drug-controlled release system loaded with gentamicin on a titanium surface, and to evaluate the in vitro drug release behaviour and antibacterial properties and biocompatibility of the controlled release system. Methods Titanium (Ti) surface was coated with poly dopamine (PDA) substrate, and then polyethylene glycol (PEG) was attached to PDA. The composite drug microsphere controlled release layer formed by gentamicin (GEN) and cross-linked starch (CSt) were subsequently covered with poly lactic⁃co⁃glycolic acid (PLGA) as a barrier to construct a Ti-GEN-Cst-PLGA anti-infective drug controlled release system. Results The hydrogel drug release system was successfully constructed. The results of in vitro anti-staphylococcus aureus (SAU) assay, anti-staphylococcus epidermidis (SEP) assay and anti-Escherichia coli (ECO) assay showed that Ti-GEN-Cst-PLGA could effectively inhibit the growth of three bacteria. Assay in the New Zealand rabbit found that Ti-GEN-Cst-PLGA could promote wound healing at the 3rd week after implantation, and the pathology assay found that the Ti-GEN-Cst-PLGA group had less inflammatory reactions and significant tissue proliferation at the endophyte contact surface. Conclusion Ti-GEN-Cst-PLGA can effectively inhibit the inflammatory response and promote wound healing, or may be a potential treatment for orthopaedic endophytes.