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OBJECTIVE To prepare zeolite imidazole framework （ZIF）-8 nanoparticles （NPs） loaded with temozolomide （TMZ） （abbreviated as TMZ@ZIF-8 NPs） drug delivery system， thus increasing drug enrichment and anti-glioma effects in lesions. METHODS After preparing ZIF-8 NPs using the room temperature solution reaction method， the impregnation method was used to prepare TMZ@ZIF-8 NPs drug delivery system. Characterization was carried out using transmission electron microscopy， laser particle size， and Fourier transform infrared spectroscopy， and dissolution and anti-tumor activity experiments in vitro and in vivo were conducted. RESULTS TMZ@ZIF-8 NPs were successfully prepared with the particle size of （126.23±7.92） nm， drug loading amount of （28.79±1.26）%， and 72 h cumulative dissolution rate of （72.36±3.62）%. The results of in vitro anti-tumor activity experiments showed that the relative cell survival rate of ZIF-8 NPs remained above 90%； the prepared TMZ@ZIF-8 NPs delivery system exhibited superior inhibition， higher uptake capacity， and better promoting apoptosis effects on the growth and proliferation of C6 cells as compared with the free TMZ. The results of in vivo anti-tumor activity experiments showed that ZIF-8 NPs were not enriched in the brain of rats， and the enrichment effect of TMZ in the brain was not significant， while TMZ@ZIF-8 NPs had a significant enrichment effect in the brain. CONCLUSIONS ZIF-8 NPs can effectively load TMZ， and successfully prepared TMZ@ZIF-8 NPs can improve TMZ uptake ability and anti-glioma effect.
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Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation， namely the Warburg effect. Even under aerobic conditions， tumor cells mainly rely on glycolysis to provide energy. Therefore， glucose transporter protein 1（GLUT1）， which is involved in the process of glucose metabolism， plays an important role in tumorigenesis， development and drug resistance， and is considered to be one of the important targets in the treatment of malignant tumors. In recent years， research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism， among which the role of GLUT1 is the most critical. In this paper， the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine（TCM） active ingredient nano-delivery system in tumor therapy， aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention（EPR） effect. In summary， the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.
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Red blood cells and platelets are widely present in the blood. They are easily isolated from the blood and relatively stable in nature, making them an ideal drug delivery vehicle. In recent years, a large number of studies have been conducted to use red blood cells and platelets to deliver antitumor drugs and achieve efficient drug delivery. Red blood cells and platelets have shown excellent results in optimizing the in vivo behavior of drugs, increasing efficacy, and reducing the dose administered. In addition, its cell membrane can be used as a coating material to improve the properties of nanodrug delivery systems and achieve biomimetic functions while reducing the toxic side effects of nanoparticles. The characteristics and preparation methods of red blood cells and platelets and their membrane materials were introduced, and their diagnostic and therapeutic applications in antitumor drug delivery was looked forward.
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Objective:The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain,such as trigemina neuralgia.This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. Methods:A modified Delphi approach was used to work for this guideline.On the issues related to the intra-prepontine cisternal targeted drug delivery technique,the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. Results:For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique,a consensus was formed on 7 topics(with an agreement rate of more than 80%),including the principles of the technique,indications and contraindications,patient preparation,surgical specifications for intra-prepontine cisternal catheter placement,analgesic dosage coordination,analgesic management,and prevention and treatment of complications. Conclusion:Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive,secure,and effective treatment.This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments,justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.
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Objective:Using atenolol as a model drug,the aim of this study was to develop a sustained and controlled transdermal drug delivery system(TDDS)based on polyethyleneimine-modified MoS2 nanoparticles(PEI-MoS2 NPs)that were responsive to near infrared(NIR)laser irradiation.Methods:The three-dimensional flower-like PEI-MoS2 NPs were successfully synthesized and further characterized by attenuated total reflection Fourier transform infrared spectroscopy,X-ray diffraction measurements,scanning electron microscopy,and transmission electron microscopy.The controlled release capacity of PEI-MoS2 NPs was examined using in vitro drug release and skin penetration experiments.Results:The PEI-MoS2 NPs exhibited a drug loading efficiency of 53.86% and high photothermal conversion ability.Moreover,the release of atenolol was enhanced by NIR stimulation with an enhancement ratio of 1.56.Conclusion:NIR-controlled PEI-MoS2 NPs was essential for the control and sustained release of drugs in TDDS.
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BACKGROUND:The imbalance of matrix synthesis and degradation is the main cause of nucleus pulposus degeneration.Small molecule drug Kartogenin(KGN)can restore the balance of matrix synthesis and degradation.Sustained release of KGN using an appropriate drug delivery system is essential for the long-term and effective treatment of KGN.OBJECTIVE:To prepare the injectable hydrogel microspheres by encapsulating KGN with gelatin methacryloyl(GelMA)by microfluidic technology and to investigate the biocompatibility and biological function of nucleus pulposus cells.METHODS:β-Cyclodextrins(β-CD)and KGN were mixed firstly and then mixed with 10%GelMA at a volume of 1:9.Injectable hydrogel microspheres GelMA@β-CD@KGN were prepared by microfluidic technology.The micromorphology of the microspheres was characterized using a scanning electron microscope.The drug release of hydrogel microspheres immersed in PBS within one month was measured.Nucleus pulposus cells were isolated from SD rats and passage 1 cells were cultured in three groups.In the control group,nucleus pulposus cells were cultured separately.In the other two groups,GelMA@β-CD microspheres and GelMA@β-CD@KGN microspheres were co-cultured with nucleus pulposus cells.Cell proliferation was detected by CCK-8 assay and cell survival was detected by live/dead cell staining.Cells were cultured by two complete media with and without interleukin-1β with two kinds of microspheres.mRNA expressions of matrix synthesis and decomposing proteins in nucleus pulposus cells were detected by RT-PCR.RESULTS AND CONCLUSION:(1)Under the scanning electron microscope,the GelMA@β-CD@KGN microspheres after lyophilization were regularly spherical,highly dispersed,uniform in size and full in shape.GelMA@β-CD@KGN microspheres sustained drug release in vitro,reaching 62%of the total drug release at 30 days.(2)Live/dead cell staining showed that GelMA@β-CD@KGN could maintain the activity of nucleus pulposus cells.CCK-8 assay showed that GelMA@β-CD@KGN could promote the proliferation of nucleus pulposus cells.(3)In the complete media with and without interleukin-1β,mRNA expression of aggrecan and type Ⅱ collagen was higher in the GelMA@β-CD@KGN microsphere group than that in the GelMA@β-CD microsphere group(P<0.05,P<0.01);mRNA expression of matrix metalloproteinase 13 and platelet reactive protein disintegrin metallopeptidase 5 was lower than that in the GelMA@β-CD microsphere group(P<0.01).(4)These findings indicate that GelMA@β-CD@KGN microspheres have good biocompatibility and sustained drug release ability.As a drug delivery system,it is a kind of biomaterial with broad application prospects.
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BACKGROUND:The combination of good biomechanical properties,controlled drug release and multi-functionality of core-shell structured nanofibers is receiving more and more attention,which also makes them promising for a wide range of applications in the field of oral tissue regeneration. OBJECTIVE:To summarize the preparation,drug loading and release mechanisms of core-shell structured nanofibers and their application in the regenerative repair of oral tissues. METHODS:A computer search of the literature collected in CNKI and PubMed from January 2000 to November 2022 was applied,and the search terms in English and Chinese were"electrospinning,core-shell structures,drug delivery systems,jaw bone regeneration,cartilage regeneration,periodontal tissue regeneration". RESULTS AND CONCLUSION:(1)There are various methods for the preparation of core-shell structured nanofibers,but the coaxial and emulsion methods of electrostatic spinning have unique advantages such as simple operation,diverse material selection and good biocompatibility.(2)Core-shell structured nanofibers can be used as bacteriostatic agents,carriers of different types of drugs,and scaffolds for cell adhesion,providing new therapeutic options for oral tissue regeneration.(3)Controlled degradation and drug release rate of core-shell structured nanofibers can better adapt to the healing process of oral tissue defect repair and achieve ideal tissue regeneration.
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BACKGROUND:Myocardial infarction is one of the most serious cardiovascular diseases at present,and the existing clinical treatment options such as thrombolytic therapy,percutaneous coronary intervention and coronary artery bypass grafting cannot fully restore the myocardial damage caused by ischemia.Stem cell-derived exosomes for the treatment of myocardial infarction have been a hot research topic in recent years,but the low yield of natural-derived exosomes,the difficulty and time consuming nature of obtaining them,and the poor homing effect have limited their clinical application.In this context,the construction of artificial exosomes as an alternative to natural exosomes has become an effective strategy to solve the above problems. OBJECTIVE:To expound the research status of artificial exosomes in the treatment of myocardial infarction,and classify them into two design modes:semi-artificial and full-artificial,and discuss the research progress and problems of the two modes,finally,make the evaluation and prospect of its clinical application in the future. METHODS:PubMed and CNKI were searched for relevant articles with"artificial exosomes,myocardial infarction,engineering"in Chinese,and"artificial exosome,hybrid exosome,myocardial infarction,nanoparticle,drug delivery system"in English.The focus of the search was from January 2017 to December 2022,and some of the classic forward literature was included.A preliminary selection was conducted through reading titles and abstracts.Repetitive studies,low-quality journals and irrelevant articles were excluded.Finally,73 articles were included for review. RESULTS AND CONCLUSION:(1)By semi-artificially modifying exosomes,whether it is the modification of targeting peptides,hybridization of biofilms or the assistance of magnetic substances,traditional exosome therapies with insufficient targeting and low retention rate and easy to be cleared by the reticuloendothelial system have improved the efficiency of traditional exosome therapy for myocardial infarction.However,these strategies have problems such as unclear modification efficiency,medical ethics,and biotoxicity.(2)Fully artificial bionic exosomes have a higher degree of design freedom compared to exosome modification,which can solve the problems of high extraction and storage difficulties of exosomes of natural origin and limitations of large-scale production;however,this artificial exosome strategy still lacks reliable preclinical data support and biosafety testing,and has not yet formed a standardized process required for large-scale production;therefore,before applying to the clinic,the artificial exosome solution as an alternative to natural exosomes still needs continuous in-depth research by researchers.
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BACKGROUND:Cartilage degeneration and subchondral bone damage are the main pathological features of osteoarthritis,and treatment based on this pathological feature will be a promising improvement for osteoarthritis. OBJECTIVE:To design and study an annotated strontium ranelate-loaded drug delivery system and to observe its therapeutic effect on promoting cartilage repair and improving subchondral bone structure in osteoarthritis. METHODS:(1)In vitro experiment:Strontium ranelate was loaded into sodium alginate/collagen hydrogel matrix to construct in situ drug delivery system,and the in vitro slow release performance of the system was characterized.Strontium ranelate-loaded sodium alginate/collagen hydrogel(experimental group)and alginate sodium/collagen hydrogel(control group)were co-cultured with bone marrow mesenchymal stem cells,respectively,and cultured cells were used as a blank control group to detect cell proliferative activity.After chondroblast-induced differentiation,saffron O staining,Alcian blue staining and RT-qPCR were performed respectively.The two hydrogels were co-cultured with osteoblasts,and the cultured cells were used as a blank control group for immunofluorescence staining and RT-qPCR.(2)In vivo experiment:A total of 18 adult SD rats were selected and the model of right posterior knee osteoarthritis was established by the method of medial meniscectomy.After 1 week,the rats were divided into three groups by the random number table method:The blank group did not receive any treatment.The control group was injected with sodium alginate/collagen hydrogel in the knee,and the experimental group was injected with strontium ranelate-loaded sodium alginate/collagen hydrogel,with 6 rats in each group.After 6 weeks,the samples were subjected to Micro-CT scanning,hematoxylin-eosin staining,saffron O-solid green staining and immunofluorescence staining. RESULTS AND CONCLUSION:(1)In vitro experiment:Strontium ranelate-loaded sodium alginate/collagen hydrogel had porous microstructure and sustainable release of strontium ranelate.At 21 days,the cumulative release reached(60.89±0.58)%.Bone marrow mesenchymal stem cell staining showed that both hydrogels had good cytocompatibility.The results of the CCK-8 assay demonstrated that strontium ranelate-loaded sodium alginate/collagen hydrogel could promote the proliferation of bone marrow mesenchymal stem cells.The results of Safranin O staining,Alcian blue staining,immunofluorescence staining and RT-qPCR exhibited that strontium ranelate-loaded sodium alginate/collagen hydrogel could promote chondrogenic differentiation of bone marrow mesenchymal stem cells.Immunofluorescence staining and RT-qPCR revealed that strontium ranelate-loaded sodium alginate/collagen hydrogel could decrease bone resorptivity by increasing the ratio of osteophosphorin/nuclear factor κB receptor activator ligand.(2)In vivo experiment:Micro-CT scan verified that compared with the blank group and control group,the subchondral bone volume fraction and bone mineral density of the knee of rats were increased in the experimental group(P<0.05,P<0.01).Histological staining displayed that compared with the blank group and control group,the knee cartilage injury was significantly reduced;the expression of type II collagen was promoted,and the expression of matrix metalloproteinase 2 protein was inhibited in the experimental group(P<0.05,P<0.01).(3)These results confirm that the strontium ranelate-loaded sodium alginate/collagen hydrogel can promote the repair of cartilage defects in osteoarthritis and reconstruct the complex interface between cartilage and subchondral bone.
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BACKGROUND:Gold nanoparticles are of great significance in the development of multifunctional transdermal drug delivery systems.Smaller gold nanoparticles can penetrate the dermis through the intercellular pathway,but are limited to their easy agglomeration and colloidal morphology,which makes it difficult to exert effects on low delivery efficiency. OBJECTIVE:To develop an ultrasound-optimized hydrogel delivery system by combining phase change nanodroplets with bio-adhesive hydrogel for percutaneous delivery of gold nanoparticles. METHODS:The ultrasound-responsive nanodroplets loaded with gold nanoparticles were prepared by the emulsion solvent evaporation method and loaded into the polydopamine-modified methylacryloyl gelatin hydrogel to prepare a composite hydrogel scaffold.The structure and chemical composition of the ultrasound-responsive nanogold carrier were characterized.The microstructure,porosity,permeability,rheology,in vitro hemostasis,and antibacterial properties of the composite hydrogel were characterized.The cell compatibility of the hydrogel scaffold was evaluated by live/dead staining,and the optimization effects of low-intensity pulsed ultrasound on the permeability,porosity,and mechanical properties of hydrogel were evaluated. RESULTS AND CONCLUSION:(1)Transmission electron microscopy and ultraviolet-visible spectroscopy proved the successful construction of nanogold carriers.The particle size and potential results demonstrated that the synthesized nanoscaled ultrasonic responsive carrier had good stability.(2)Live/dead cell staining proved that the prepared composite hydrogel scaffold had certain biocompatibility.(3)Scanning electron microscopy exhibited that the prepared composite hydrogel scaffold had a porous network structure,and numerous pores of about 2 μm appeared inside the macropores after the addition of nanodroplets and ultrasonic irradiation.The permeability experiment displayed that low-intensity pulsed ultrasound could optimize the porosity and permeability of hydrogel materials.The hemostatic performance of the composite hydrogel scaffold was better than that of the hemostatic sponge and polydopamine@methylacrylylated gelatin hydrogel scaffold.Under the irradiation of low-intensity pulsed ultrasound,the composite hydrogel scaffolds had good antioxidant effects and antibacterial properties.(4)Thermal imaging results manifested that gold nanoparticles were encapsulated in ultrasound-responsive nanobubbles,and more uniform dispersion could be obtained under ultrasonic excitation.(5)The results of the mechanical property test demonstrated that the storage modulus of the hydrogel increased before and after loading gold nanoparticles-nanodroplets,which showed stronger mechanical properties.The elongation at break was 122%,and the ductility was better than that without gold nanoparticles-nanodroplets(P<0.05).(6)These findings indicate that the composite hydrogel scaffold has good biocompatibility,antibacterial property,oxidation resistance,and hemostatic effect.
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BACKGROUND:Electrospun porous nanofiber exhibits excellent properties and designability.It is an effective way to control the release of traditional Chinese medicine and improve the bioavailability to design an advanced drug delivery system,which has a broad application prospect. OBJECTIVE:To review the construction methods of the electrospinning drug delivery system of traditional Chinese medicine and its related research progress in the medical field. METHODS:The literature search was performed in CNKI,PubMed,and Web of Science databases with the search terms"electrospinning,traditional Chinese medicine,drug carrier,drug delivery system,tissue engineering,dressing"in both English and Chinese for articles published from 2013 to 2023.Finally,62 articles were included in this review. RESULTS AND CONCLUSION:(1)The key elements of the electrospinning drug delivery system of Chinese medicine preparation are substrate material,traditional Chinese medicine composition,and drug loading method.(2)The preparation of the electrospinning drug delivery system of Chinese medicine can be carried out according to the application scenario and therapeutic purpose.Firstly,the types of Chinese medicine are selected,then the polymer matrix and solution suitable for them are selected,and finally,the fiber structure is designed according to the drug release requirements and the appropriate drug loading method is adopted.(3)At present,the medicinal agents used are mainly plant Chinese medicine,and there is a lack of systematic research on animal and mineral Chinese medicine.(4)Blended drug loading is the most studied and applied drug loading method,and its drug release characteristics and adaptation scenarios are constantly expanded by optimizing the physicochemical properties of the solution and selecting the diversity of loaded substances.Multilayer fibers with different compositions and properties can be prepared by coaxial,multi-axis,and sequential electrospinning methods,which have broad development prospects.(5)The early application of the electrospinning drug delivery system of Chinese medicine focused on medical dressings according to the antibacterial and hemostatic functions.In recent years,it has been studied in the field of tissue engineering because some components of traditional Chinese medicine can promote cell adhesion,proliferation,and differentiation.(6)At present,the research mainly focuses on the characterization and optimization of loading materials,processes,physicochemical properties,and biological properties,but the research on the mechanism is less.Its clinical application has not been widespread;the adverse reactions in vivo and the interaction between its degradation behavior and drug release behavior are still unknown.(7)Future studies need to consider:We should expand the application of Chinese medicine by improving the physicochemical properties and increasing the purification of Chinese medicine extracts.We need to comprehensively study the therapeutic effects and application mechanisms of Chinese medicine,and clarify the interaction of degradation behavior and drug release behavior,to achieve a more perfect combination and application of Chinese medicine and electrospinning nanofibers under a more accurate mechanism.
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BACKGROUND:In the treatment strategy of chronic osteomyelitis,the local antibiotic slow-release system has attracted much attention in the clinic due to the long-term release of effective concentrations of antibiotics to control the infection,and at the same time,the ability to repair bone defects caused by debridement. OBJECTIVE:To summarize the research status of antibiotic sustained-release carriers prepared from biodegradable polymer-based materials for the treatment of osteomyelitis,and analyze the limitations and challenges. METHODS:Chinese and English key words were"polymer,composite material,osteomyelitis,infectious bone defect,drug delivery systems,antibiotic sustained-release system,3D printing".Relevant articles were searched in PubMed,Web of Science,CNKI,and WanFang databases from January 2015 to August 2023.4 351 articles were obtained in the initial examination,and 87 articles were analyzed after screening. RESULTS AND CONCLUSION:Polymer-based materials have been widely studied in the preparation of antibiotic sustained-release carriers due to their good biocompatibility,biodegradability,thermal stability,and easy processing.However,the antibiotic slow-release carrier composed of a single polymer material cannot meet the standard of infectious bone defect repair materials due to the lack of biomechanical properties.The organic-inorganic composite material carrier,which simulates the formation of natural bone tissue structure,is expected to meet this standard.3D printing technology can precisely control the size,geometry,and spatial distribution of the interconnecting pores of the carrier,and can load the effective concentration of antibiotics to achieve controlled release.The polymer material is the most suitable for 3D printing because of its good thermal stability and plasticity.Therefore,the author believes that on the basis of new biodegradable organic-inorganic composite materials and combined with 3D printing technology,the material-structure-function integrated composite antibiotic slow-release carrier to simulate the extracellular matrix microenvironment is expected to become a novel research direction in the treatment of chronic osteomyelitis.
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BACKGROUND:Currently,there are few kinds of drugs to treat kidney diseases,and many systemic drugs have some problems,such as serious side effects,rapid degradation in the body circulation and so on.At present,active targeting of nanoparticles has become a hot spot in the field of drug delivery,and the exploration of the pathological mechanism related to active targeting of nanoparticles is becoming more and more abundant. OBJECTIVE:To summarize the active targeting strategies in common renal diseases. METHODS:The first author and the second author searched CNKI,Wanfang,VIP,and PubMed databases using"nanoparticles,active targeting,target,kidney,kidney disease"as English key words and"nanoparticles,nanoparticles,targeting,active targeting,kidney disease,kidney"as Chinese key words.All relevant articles published before July 2,2023 were retrieved,screened,concluded,and summarized.Finally,62 articles were included for the summary. RESULTS AND CONCLUSION:The active targeting effect of nanoparticles has been studied in many common kidney diseases.The mechanism of active targeting is mainly the binding of ligands and receptors,by modifying the ligand on the nanoparticles to specifically target the receptor on the cells in the kidney;in which way active targeting is realized.Under different renal pathological conditions,the pathological changes of specific kidney sites may become the key breakthrough point to achieve active targeting.Although kidney-targeting nanoparticles have shown promise in the treatment of nonneoplastic kidney diseases,but it is still in the experimental phase in animals,and it is still a long way from applying these results to medical work.
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Ahmed glaucoma drainage valve (AGV) implantation is one of the main methods for the treatment of refractory glaucoma with a higher success rate than conventional filtration surgery.However, as a foreign body, the AGV often causes hyperplasia of scar tissue in the filtration area, wrapping around the drainage plate, thereby inhibiting aqueous fluid outflow and causing the intraocular pressure to rise again, leading to surgical failure.Although multiple injections of anti-metabolic drugs during and after AGV implantation can inhibit postoperative scarring, multiple postoperative subconjunctival injections will not only cause discomfort to patients, but also lead to complications.Therefore, it is necessary to improve the AGV to avoid repeated injection of the drug, achieve slow local release of the drug, and reduce the foreign body reaction of AGV at the same time.Recently, the development of new materials, such as Ologen collagen, poly (2-hydroxyethyl methacrylate), poly lactic-co-glycolic acid and opal shale and new techniques provides new methods to inhibit the scarring of filtration area after AGV implantation.This article reviews the methods and progress of inhibition of scar formation in filtration area from the aspects of development of AGV drainage plate materials, construction of drug delivery system of AGV combined with new materials, and improvement of AGV drainage plate structure.
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In recent years,due to the development of disciplines such as molecular biology,cell biology,and materials science,the research of targeted therapy drugs has become a hot spot.Compared with conventional drugs,targeted therapy drugs can selectively increase the concentration and effectively reduce the toxic side effects of drugs in target tissues,which is an ideal way of drug delivery.Nanomaterial is receiving more attention for its superior performance in animals.The application and develop-ment of nanocrystals in targeted drug delivery systems has effectively broken the limitation of insoluble drugs and plays an indis-pensable role in drug delivery systems.In this paper,we briefly reviewed the characteristics and classification of targeted therapy drugs and the application of nanocrystals in pharmaceutical research to provide a reference for the related research.
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Skin modeling of transdermal drug delivery system refers to experimental models that mimic the structure and function of human skin to explore and evaluate absorption,penetration,and efficacy of medicines in transdermal drug delivery.It provides an alternative to traditional human skin experiments and reduces the use of human skin in medical research,which is convenient,controllable,and cost effective.For skin models of transdermal drug delivery systems,this article introduces commonly used animal skin models,artificial skin models,and recombinant human skin models from the perspective of the transdermal absorption pathway of medicines,and analyzes their advantages,disadvantages,and applications so provide references the research and development of transdermal formulations and topical therapies.
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Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.
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Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca2+-interfering therapeutic effect. Based on these characteristics, amorphous calcium carbonate (ACC), as a brunch of calcium-based biomaterials, has the potential to become a widely used biomaterial. Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However, the standalone presence of ACC is unstable in vivo. Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination. ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo, such as Ca2+ with an immune-regulating ability and CO2 with an imaging-enhancing ability. Owing to these characteristics, ACC has been studied for self-sacrificing templates of carrier construction, targeted delivery of oncology drugs, immunomodulation, tumor imaging, tissue engineering, and calcium supplementation. Emphasis in this paper has been placed on the origin, structural features, and multiple applications of ACC. Meanwhile, ACC faces many challenges in clinical translation, and long-term basic research is required to overcome these challenges. We hope that this study will contribute to future innovative research on ACC.
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Diseases of ocular fundus are the leading causes of severe vision impairment or even blindness in patients worldwide, and the medical treatments are seriously limited by the difficulty of therapeutic drugs entering the fundus due to the various physiological barriers. Nano-drug delivery systems, with their nanoscale size and large surface area, can be loaded with therapeutic drugs of different physicochemical properties and modified with various surface active substances, which can not only improve the solubility and penetration of the drugs, but also protect biologic drugs from degradation and improve the biological safety and bioavailability, as well as deliver therapeutic drugs to specific ocular targets. All of these make the therapeutic potential enormous. Currently, more and more studies have been carried out to take advantage of nanomaterials for the treatment of different fundus diseases, including neurodegenerative diseases, fundus neovascularization, endophthalmitis and fundus tumors. This review analyzes the challenges and barriers faced by different routes of drug administration in the treatment of fundus diseases, the physicochemical properties of common nano-drug delivery systems that have been studied in related fields, and further summarizes the progress, advantages, limitations, and future directions of the application of various nano-drug delivery systems for the treatment of ocular fundus diseases in recent years.
RESUMO
Este estudo avaliou a eficácia in vitro e in vivo de mantas de nanofibras (NF) de policaprolactona (PCL) incorporadas com nistatina (NIS) no tratamento da estomatite protética (EP) em modelos animais. NF foram sintetizadas com diferentes concentrações de NIS, totalizando quatro soluções: PCL puro, PCL/NIS 0,045 g, PCL/NIS 0,090 g e PCL/NIS 0,225 g. A liberação da NIS foi analisada por espectroscopia Ultravioleta-Visível. A capacidade das mantas de inibirem o biofilme de Candida albicans, principal fator etiológico da EP, dividindo-se cinco grupos (N=5) compostos por um grupo com controle de células de C. albicans e com PCL puro, além das três concentrações de NIS. A seguir, foi analisada a viabilidade celular em queratinócitos humanos (HaCat) por meio do teste colorimétrico de resazurina. Cinco grupos foram divididos (N=10): controle celular, PCL puro e as três concentrações de NIS. Em modelos animais de ratos Wistar albinos (N=18), dispositivos palatinos (DP) de resina acrílica foram confeccionados simulando próteses totais e utilizados para a indução da EP. Para isso, DP contaminados com C. albicans foram cimentados na região molar da cavidade bucal dos animais e permaneceram em boca por 48 h. Após esse período, os DP foram removidos e os animais foram divididos em três grupos: (C) controle; (B1) com tratamento por mantas de PCL/NIS 0,045 g e (B2) PCL/NIS 0,225 g, com N=6. Então novos DP, livres de contaminação, foram cimentados na cavidade oral dos animais e permaneceu por mais 48 h. Após esse período, os animais foram eutanasiados, a contagem de UFC/ mL foi realizada e os palatos foram coletados para a análise histológica. A curva padrão de NIS obtida apresentou R2 de 0,99. As três concentrações de NF apresentaram liberação de NIS, com pico no tempo de 6 h e valores de 66,26 µg/ mL para PCL/NIS 0,045 g, de 333,87 µg/ mL para PCL/NIS 0,090 g e 436,51 µg/ mL para PCL/NIS 0,225 g, constantes até o fim do experimento. Os grupos com NIS reduziram em 2,5 log10 de crescimento do biofilme fúngico em relação aos grupos sem tratamento, Controle e PCL, sem diferença estatística significativa. Não foi observada citotoxicidade nas células HaCat, com viabilidade celular de 93,7% para PCL/NIS 0,045 g, 72,6% para PCL/NIS 0,090 g e 72,4% para PCL/NIS 0,225 g. A indução da EP nos três grupos foi possível e, porém, sem redução significativa na contagem de UFC/ mL de C. albicans nos grupos B1 e B2. Na análise histológica do grupo C pôde-se observar infiltração de hifas de Candida na camada queratinizada, presença de células inflamatórias formando micro abscessos e um discreto infiltrado inflamatório no tecido conjuntivo subjacente ao epitélio infectado. Nos grupos B1 e B2 não foram encontradas alterações epiteliais, concluindo-se que as NF demonstraram atividade antifúngica in vitro e foram efetivas na prevenção da penetração de hifas no tecido palatino de animais com DP (AU)
This study evaluated the in vitro and in vivo efficacy of nanofiber (NF) mats of polycaprolactone (PCL) incorporated with nystatin (NIS) in the treatment of denture stomatitis (DS) in animal models. NFs were synthesized with different concentrations of NIS, totaling four solutions: pure PCL, PCL/NIS 0.045 g, PCL/NIS 0.090 g, and PCL/NIS 0.225 g. The release of NIS was analyzed by Ultraviolet-Visible spectroscopy. The ability of the mats to inhibit Candida albicans biofilm, the main etiological factor of DS, was assessed by dividing five groups (N=5) composed of a group with C. albicans cell control and with pure PCL, in addition to the three concentrations of NIS. Next, cell viability in human keratinocytes (HaCat) was analyzed using the resazurin colorimetric test. Five groups were divided (N=10): cell control, pure PCL, and the three concentrations of NIS. In albino Wistar rat animal models (N=18), palatal devices (PD) made of acrylic resin were fabricated to simulate total prostheses and used to induce DS. For this, PD contaminated with C. albicans were cemented in the molar region of the animals' oral cavity and remained in the mouth for 48 hours. After this period, the PDs were removed, and the animals were divided into three groups: (C) control; (B1) treated with PCL/NIS 0.045 g mats, and (B2) PCL/NIS 0.225 g, with N=6. Then new, uncontaminated PDs were cemented in the animals' oral cavity and remained for another 48 hours. After this period, the animals were euthanized, UFC/ mL counts were performed, and the palates were collected for histological analysis. The standard NIS curve obtained showed an R2 of 0.99. The three concentrations of NF showed NIS release, with a peak at 6 h and values of 66.26 µg/ mL for PCL/NIS 0.045 g, 333.87 µg/ mL for PCL/NIS 0.090 g, and 436.51 µg/ mL for PCL/NIS 0.225 g, remaining constant until the end of the experiment. The groups with NIS reduced fungal biofilm growth by 2.5 log10 compared to the untreated groups, Control and PCL, with no significant statistical difference. No cytotoxicity was observed in HaCat cells, with cell viability of 93.7% for PCL/NIS 0.045 g, 72.6% for PCL/NIS 0.090 g, and 72.4% for PCL/NIS 0.225 g. Induction of DS in the three groups was possible; however, there was no significant reduction in UFC/ mL counts of C. albicans in groups B1 and B2. Histological analysis of group C revealed infiltration of Candida hyphae in the keratinized layer, presence of inflammatory cells forming micro abscesses, and a discreet inflammatory infiltrate in the connective tissue underlying the infected epithelium. No epithelial alterations were found in groups B1 and B2, concluding that NFs demonstrated in vitro antifungal activity and were effective in preventing hyphal penetration into palatal tissue in animals with PD.(AU)