Solely abluminal drug release from coronary stents could possibly improve reendothelialization.

OBJECTIVES: To compare a new stent with an asymmetric coating, eluting the drug to the abluminal surface, to a stent with a conventional coating eluting the drug both to the luminal and the abluminal side. BACKGROUND: Stents with asymmetric coating, eluting the drug to the vessel wall (BPSES-A), could potentially give faster reendothelialization after percutaneous coronary interventions (PCI) and decrease in in-stent thrombosis and late restenosis. METHODS: BPSES-A, conventional coated stents (BPSES-C), biodegradable polymer stents without drug (BPS, for control), and bare metal stents (BMS, for control) were implanted into the coronary arteries of 38 pigs (75 stents). Pigs were sacrificed after 4, 12, and 24 weeks. Quantitative coronary angiography was used to compare in-stent late lumen loss (LLL) and electron microscopy was used to reveal levels of reendothelialization. RESULTS: The stents were all successfully implanted. LLL of BPSES-A, BPSES-C, BMS, and BPS were 0.56 ± 0.51, 0.60 ± 0.58, 0.89 ± 0.43, and 1.68 ± 0.30 mm, respectively, after 4 weeks. LLL of BPSES-A and BPSES-C were 0.63 ± 0.53 and 0.69 ± 0.24 mm, respectively, after 12 weeks. LLL of BPSES-A, BPSES-C, and BMS were 0.42 ± 0.15 m, 0.56 ± 0.28 mm, and 0.99 ± 0.13 mm, respectively, after 24 weeks. The scaling of reendothelialization was as follows: after 4 weeks BMS > = BPS > BPSES-A > BPSES-C, after 12 weeks BPSES-A > BPSES-C, and after 24 weeks BMS > BPSES-A > BPSES-C. Reendothelialization was better in BPSES-A than BPSES-C (P < 0.05). There was no correlation between LLL and reendothelialization (P = 0.42). CONCLUSION: Asymmetric coating of coronary stents might be helpful to improve reendothelialization. © 2016 Wiley Periodicals, Inc.

No Effect of Rapamycin on Cardiac Adhesion Formation: A Drug-Loaded Bioresorbable Polylactone Patch in a Porcine Cardiac Surgical Model.

BACKGROUND: The fusing of the epicardium and sternum due to adhesion is a common problem during repeated cardiac surgery and carries with it an increased risk of bleeding. The use of barriers and patches has been tested to prevent the formation of adhesions, but the very presence of a patch can provoke adhesion formation. The objective of this study was, therefore, to investigate both biodegradable and bioresorbable polylactone patches [(polycaprolactone-poly(ethylene oxide)-polycaprolactone tri-block copolymer (PCE)]. The patches were also tested with a controlled release of rapamycin, which prevents cell migration and extracellular matrix deposition. The clinical effectiveness of rapamycin in pericardial patches has not previously been examined. MATERIALS AND METHODS: Three groups of 6 female Danish Landrace pigs underwent sternotomy and abrasion of the epicardium, before being randomized to either group 1--the control group (with no patch), group 2--PCE patch implanted between the sternum and epicardium, or group 3--PCE patch and slow-release 1.6-mg rapamycin. After a median time period of 26 days, the pigs were euthanized and their hearts removed en bloc with the sternum, for macroscopic, histological and pathological examination. RESULTS: Upon macroscopic examination, a significantly lower degree of adhesion in group 2, as compared to group 1 (p < 0.05), was found. Histological analysis of the tissues showed significantly more fibrosis, inflammation and foreign body granulomas (p < 0.05) in both group 2 and group 3, when compared to group 1. CONCLUSION: A PCE patch following sternotomy in animal subjects reduces postoperative macroscopic adhesions without reducing microscopic fibrosis or inflammation. Loading the patch with rapamycin was found not to increase the antifibrotic effect.

Fabrication and cell affinity of biomimetic structured PLGA/articular cartilage ECM composite scaffold.

An ideal scaffold for cartilage tissue engineering should be biomimetic in not only mechanical property and biochemical composition, but also the morphological structure. In this research, we fabricated a composite scaffold with oriented structure to mimic cartilage physiological morphology, where natural nanofibrous articular cartilage extracellular matrix (ACECM) was used to mimic the biochemical composition, and synthetic PLGA was used to enhance the mechanical strength of ACECM. The composite scaffold has well oriented structure and more than 89% of porosity as well as about 107 µm of average pore diameter. The composite scaffold was compared with ACECM and PLGA scaffolds. Cell proliferation test showed that the number of MSCs in ACECM and composite scaffolds was noticeably bigger than that in PLGA scaffold, which was coincident with results of SEM observation and cell viability staining. The water absorption of ACECM and composite scaffolds were 22.1 and 10.2 times respectively, which was much higher than that of PLGA scaffolds (3.8 times). The compressive modulus of composite scaffold in hydrous status was 1.03 MPa, which was near 10 times higher than that of hydrous ACECM scaffold. The aforementioned results suggested that the composite scaffold has the potential for application in cartilage tissue engineering.

Clinical Study on Electronic Medical Neuroelectric Stimulation Based on the Internet of Things to Treat Epilepsy Patients with Anxiety and Depression.

With the continuous development and improvement of the level of medical technology in our country in recent years, the treatment of epilepsy has been constantly updated and developed. Nerve electrical stimulation is considered to be a very effective method for treating epilepsy with anxiety and depression. There are many traditional methods for the treatment of epilepsy. For example, vagus nerve stimulation (VNS) has been applied earlier, and the therapeutic effect has been confirmed, but it will cause serious complications and is easier to be uncomfortable; deep brain stimulation for epilepsy is still in the immature stage, and there is no final conclusion. Therefore, this article proposes a clinical study on the treatment of patients with epilepsy with anxiety and depression based on the electronic medical nerve stimulation of the Internet of Things. First of all, this article uses the literature method to study the causes of epilepsy and previous treatment methods. Then, we designed an experimental study of epilepsy with depression based on the Internet of Things electronic medical neuroelectric stimulation therapy and selected the core quality of life questionnaire, SDS, and SAS as observation indicators. Finally, the comparison of epilepsy symptoms and depression and anxiety between the control group and the observation group before and after treatment was analyzed. The results of the experiment showed that, among the 50 subjects in the study, the observation group that used electrical nerve stimulation therapy had 5 people who stopped seizures after treatment, accounting for 10%, while in the control group of traditional drug treatment methods, after treatment, only one person stopped the seizure, accounting for 2%. In addition, the SAS and SDS scores of the observation group were also lower than those of the control group. Therefore, the use of nerve electrical stimulation to treat epilepsy with anxiety and depression symptoms has better performance and can help patients recover as soon as possible.

In vivo evaluation of composites of PLGA and apatite with two different levels of crystallinity.

The cortical bone response towards poly(lactide-co-glycolide) (70/30) (PLGA) (70/30)/apatite complex scaffolds with different levels of crystallinity was investigated. Apatite with different levels of crystallinity, Ca-deficient hydroxyapatite (CDHA), which has a low crystallinity, and a mixture of carbonated hydroxyapatite (CHA) and CDHA, which has a higher crystallinity, were prepared from an aqueous mixture of Ca-EDTA complex, H(2)O(2), H(3)PO(4), and NH(4)OH. Two porous PLGA(70/30)/apatite composite scaffolds, composite scaffold A (containing low crystallinity CDHA) and composite scaffold B (containing the higher crystallinity CHA/CDHA mixture), were prepared. Afterwards, pure porous PLGA and the two composite scaffolds were implanted into the cortical bone of rabbit tibiae for 12 weeks. High-resolution microfocus X-ray computed tomography and histological examinations revealed a better bone response for composite scaffold A compared with PLGA and composite scaffold B. For composite scaffold A, the original bone defect was almost filled with new bone. Quantitative analysis revealed that composite scaffold A produced a significantly greater amount of new bone. The present study demonstrated that the level of apatite crystallinity influences bone response. A PLGA/apatite porous composite with a low level of apatite crystallinity shows promise as a bone substitute or scaffold material for bone tissue engineering.

Surface Modification of Aliphatic Polyester to Enhance Biocompatibility.

Aliphatic polyester is a kind of biodegradable implantable polymers, which shows promise as scaffolds in tissue engineering, drug carrier, medical device, and so on. To further improve its biocompatibility and cell affinity, many techniques have been used to modify the surface of the polyester. In the present paper, the key factors of influencing biocompatibility of aliphatic polyester were illuminated, and the different surface modification methods such as physical, chemical, and plasma processing methods were also demonstrated. The advantages and disadvantages of each method were also discussed with the hope that this review can serve as a resource for selection of surface modification of aliphatic products.

An abluminal biodegradable polymer sirolimus-eluting stent versus a durable polymer everolimus-eluting stent in patients undergoing coronary revascularization: 3-year clinical outcomes of a randomized non-inferiority trial.

The Cordimax stent has proved non-inferior to the Cypher Select durable polymer sirolimus-eluting stent for the primary endpoint of angiographic in-stent late luminal loss and in-stent mean diameter stenosis at 9 months. The trial was designed to compare the efficacy and safety of the Cordimax stent with the Xience V stent in patients undergoing coronary revascularization. This randomized, multicenter trial enrolled 3697 patients treated with Cordimax stent (2460 patients) and Xience V stent (1237 patients). The primary efficacy endpoint was a target-lesion failure (TLF) at 1 year and the primary safety endpoint was a composite of death or myocardial infarction (MI) at 3 years. 3399 patients (91.9%) completed 3-year follow-up. At 1 year, the primary efficacy endpoint occurred in 86 (3.5%) patients in the Cordimax group versus 40 (3.2%) patients in the Xience V group (0.3% absolute risk difference, 95% CI -1.0-1.5%, Pnon-inferiority < 0.0001). At 3 years, the primary safety endpoint occurred in 39 (1.6%) patients in the Cordimax group versus 19 (1.5%) patients in the Xience V group (0.05% absolute risk difference, 95% CI -0.8-0.9%, Pnon-inferiority < 0.0001). The incidence of target lesion revascularization was low in Cordimax group compared with Xience V group (3.6% versus 5.1%, P = 0.03). There were no differences between Cordimax and Xience V in terms of Cardiac death (0.3% versus 0.4%, P = 0.70), myocardial infarction (1.2% versus 0.9%, P = 0.37), and the stent thrombosis (0.4% versus 0.6%, P = 0.61). In conclusion, safety and efficacy outcomes of Cordimax stent were non-inferior to the Xience V stent 3 years after stent implantation.

The immobilization of basic fibroblast growth factor on plasma-treated poly(lactide-co-glycolide).

In this study, possibility of the method of immobilization of basic fibroblast growth factor (bFGF) on polylactone-type polymer scaffolds via plasma treatment was investigated. To introduce acid carboxylic functional groups on the surface of the polymer matrix, poly(lactide-co-glycolide) (PLGA) film was treated with carbon dioxide (CO2) plasma and then incubated in a phosphate buffer saline (PBS, pH 7.4) solution of bFGF. The bFGF binding efficiency to the CO2 plasma-treated PLGA (PT-PLGA) films under different treating parameters was investigated and compared. It was found bFGF binding efficiency to PLGA was enhanced by CO2 plasma treatment. The binding efficiency of bFGF to PLGA was variational with CO2 plasma treating time and it reached a maximum after a treating time of 20min under the power of 20W. The changes of surface chemistry and surface topography induced by CO2 plasma treatment played main roles in improving binding efficiency. Bound bFGF was released continuously from the films for up to 7 days in vitro. The stability of bFGF immobilized on PLGA film via CO2 plasma treatment was tested further under dynamic conditions by a Parallel Plate Flow Chamber. Mouse 3T3 fibroblasts were cultured on the bFGF bound PLGA with a prior plasma treatment (20W, 20min) (PT-PLGA/bFGF) film, which showed that bFGF released from PT-PLGA/bFGF film was bioactive. Adhesion and growth of cells on PLGA scaffolds were greatly improved by immobilization of bFGF on them. Therefore, the method of CO2 plasma treatment combining bFGF anchorage not only was usable in delivering bFGF, but also could be applied extensively for surface modification of scaffolds in tissue engineering.

Preparation and cell affinity of microtubular orientation-structured PLGA(70/30) blood vessel scaffold.

In this study, a kind of microtubular orientation-structured blood vessel mimicking natural structure was fabricated with poly(lactide-co-glycolide)(70/30) (PLGA(70/30)) solutions in 1,4-dioxane by an improved thermal-induced phase separation (TIPS) technique. The effect of main factors of the TIPS technique, such as environmental temperature, temperature gradient and concentration of the polymer solution on the structure and morphology of formed vessel scaffold was investigated. It was observed that the outer-wall of the scaffold became thick obviously and the microtubules neighboring the outer-wall became disordered with environmental temperature increasing. The diameter of microtubules of vessel scaffolds reduced with temperature gradient increasing or concentration of the polymer solution increasing. By controlling parameters of the TIPS, the scaffolds with various morphologies could be manufactured, which had different diameters of microtubules. On the other hand, inner-diameter and outer-diameter of the vessel scaffolds could be controlled by adjusting size of the polyethylene mould. Cell affinity of the scaffolds was tested in vitro by using A10 cell as model cells. Results showed that the cells grew well in the vessel scaffolds which were modified by ammonia plasma treatment and then anchored with collagen. The cells could array along the direction of the microtubules.

A cartilage ECM-derived 3-D porous acellular matrix scaffold for in vivo cartilage tissue engineering with PKH26-labeled chondrogenic bone marrow-derived mesenchymal stem cells.

We developed a natural, acellular, 3-D interconnected porous scaffold derived from cartilage extracellular matrix (ECM). Human cartilage was physically shattered, then decellularized sequentially with use of hypotonic buffer, TritonX-100, and a nuclease solution and made into a suspension. The scaffold was fabricated by simple freeze-drying and cross-linking techniques. On histology, scaffolds showed most of the ECM components after removal of the cell fragments, and scanning electron microscopy revealed a 3-D interconnected porous structure. Cellular viability assay revealed no cytotoxic effects. In vitro study showed that the novel scaffold could provide a suitable 3-D environment to support the adheration, proliferation and differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) to chondrocytes in culture with chondrogenic medium after 21 days. Chondrogenically induced BMSCs labeled with fluorescent dye PKH26 were then grown on scaffolds and implanted subcutaneously into nude mice. Four weeks later, cartilage-like tissue formed, with positive staining for Safranin O, tuoluidine blue and collagen II. Cells in the samples seemed to confirm that they originated from the labeled BMSCs, as confirmed by in vivo fluorescent imaging and immunofluorescence examination. In conclusion, the cartilage ECM-derived porous scaffold shows potential as biomaterial for cartilage tissue engineering, and PKH26 fluorescent labeling and in vivo fluorescent imaging can be useful for cell tracking and analyzing cell-scaffold constructs in vivo.

Effect of different biomedical membranes on alkali-burned cornea.

OBJECTIVE: To evaluate the effects of different biomedical membranes on alkali-burned cornea in vivo. METHODS: 12 New Zealand rabbits were chosen and randomly divided into four groups. The right cornea of each rabbit was made into an alkali-burned model with 1 mmol/l NaOH. Poly-D,L-lactic acid (PDLLA), PDLLA modified with collagen (PDLLA/collagen) and PDLLA modified with chitosan (PDLLA/chitosan) membranes were transplanted onto the alkali-burned corneas for evaluation. Clinical evaluations were performed daily with a slit lamp. On the 12th day after surgery, the progress in wound healing was compared by clinical and histological examination. The reepithelialization of each cornea was evaluated with fluorescein staining and 3 corneas of each group were excised to observe histological changes such as corneal wound healing, inflammation and collagen synthesis. RESULTS: The wound healing rate of the PDLLA/chitosan group was higher than in the other groups. A more orderly arrangement of collagen and mild inflammation was observed. The control group had the next best performance, while the PDLLA/collagen and PDLLA alone treatment groups showed the worst results. CONCLUSION: PDLLA/chitosan promoted wound healing of alkali-burned corneas in vivo and decreased scar tissue formation, while the effect of the PDLLA/collagen and PDLLA membranes was to promote corneal ulcers, which suggests that PDLLA/chitosan membrane transplantation is a potential effective strategy for treatment of alkali-burned cornea.

[Fabrication and characteristics of oriental poly (lactic-co-glycolic acid) scaffold: a preliminary study].

OBJECTIVE: To explore the method of fabricating oriental scaffolds and investigate the biocompatibility of the scaffolds as well as cells distribution within the scaffolds in vitro. METHODS: The oriental poly (lactic-co-glycolic acid) (PLGA) scaffolds were fabricated with modified emulsion-phase separation method. The scaffolds were treated with plasma and then anchored with collagen I. Articular chondrocytes were loaded into the scaffolds. The growth status and distributing characteristic of the cells were investigated by environmental scanning electron microscope. RESULTS: The scaffold was well compatible with the articular chondrocytes. The cells could reach to 2.5 mm depth with unilateral loading. The cells distributed evenly in the scaffold and lined along the inner pipes. CONCLUSIONS: The oriental scaffold fabricated could significantly promote the distributing characteristics of the chondrocytes. The vertical alignment of the chondrocytes within the scaffold is closely similar to that of articular cartilage.

Combining oxygen plasma treatment with anchorage of cationized gelatin for enhancing cell affinity of poly(lactide-co-glycolide).

Surface characteristics greatly influence attachment and growth of cells on biomaterials. Although polylactone-type biodegradable polymers have been widely used as scaffold materials for tissue engineering, lack of cell recognition sites, poor hydrophilicity and low surface energy lead to a bad cell affinity of the polymers, which limit the usage of polymers as scaffolds in tissue engineering. In the present study, surface of poly (L-lactide-co-glycolide) (PLGA) was modified by a method of combining oxygen plasma treatment with anchorage of cationized gelatin. Modification effect of the method was compared with other methods of oxygen plasma treatment, cationized gelatin or gelatin coating and combining oxygen plasma treatment with anchorage of gelatin. The change of surface property was compared by contact angles, surface energy, X-ray photoelectron spectra (XPS), attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM) measurement. The optimum oxygen pretreatment time determined by surface energy was 10 min when the power was 50 W and the oxygen pressure was 20 Pa. Analysis of the stability of gelatin and cationized gelatin anchored on PLGA by XPS, ATR-FTIR, contact angles and surface energy measurement indicated the cationized gelatin was more stable than gelatin. The result using mouse NIH 3T3 fibroblasts as model cells to evaluate cell affinity in vitro showed the cationized gelatin-anchored PLGA (OCG-PLGA) was more favorable for cell attachment and growth than oxygen plasma treated PLGA (O-PLGA) and gelatin-anchored PLGA (OG-PLGA). Moreover cell affinity of OCG-PLGA could match that of collagen-anchored PLGA (AC-PLGA). So the surface modification method combining oxygen plasma treatment with anchorage of cationized gelatin provides a universally effective way to enhance cell affinity of polylactone-type biodegradable polymers.

The effect of oxygen plasma pretreatment and incubation in modified simulated body fluids on the formation of bone-like apatite on poly(lactide-co-glycolide) (70/30).

In this study, biodegradable poly(lactide-co-glycolide) (PLGA) (70/30) films and scaffolds were first treated with oxygen plasma and then incubated in a modified simulated body fluid 1.5SBF0 to prepare a bone-like apatite layer. The formation of the apatite and its influence on osteoblast-like cells growth were investigated. It was found that the bone-like apatite formability of PLGA(70/30) was enhanced by plasma pretreatment. The changes of surface chemistry and surface topography induced by oxygen plasma treatment were both effective for apatite formation. The apatite formability increased with increasing plasma-treating time. Under a treating condition of 20 W for 30 min, oxygen plasma treatment could penetrate into the inner scaffold. After 6 days incubation, the apatite formed in plasma-treated scaffold was better distributed than in untreated scaffold, and the weight and mechanical strength of the plasma-treated scaffold were both enhanced. Compared with PLGA(70/30), the apatite layer formed on oxygen plasma-treated PLGA(70/30) surface enhanced adhesion and proliferation of OCT-1 osteoblast-like cell, but had no significant effect on cell's ALP activity at day 7. A prolonged investigation is being in process to further verify the bone-like apatite effects on osteogenic differentiation.

Porous morphology, porosity, mechanical properties of poly(alpha-hydroxy acid)-tricalcium phosphate composite scaffolds fabricated by low-temperature deposition.

Tissue engineering is expected to construct complicated hominine organs composed of many different types of cells. One of the key points is the accurate controlling of scaffold material and porous morphology point by point. A new direct rapid prototyping process called low-temperature deposition manufacturing (LDM) was proposed to fabricate scaffolds. The new process integrated extrusion/jetting and phase separation and therefore could fabricate scaffolds with hierarchical porous structures creating a wonderful environment for the growth of new tissue. The interconnected computer-designed macropores allow cells in the new tissue to grow throughout the scaffold. Also, the parameter-controlled micropores let nutrition in and metabolic wastes out. The macrocellular morphology, microcellular morphology, porosity, and mechanical properties of the poly(alpha-hydroxy acid)-TCP composite scaffolds prepared by the proposed method are investigated. These scaffolds with high controllability would potentially play an important role in tissue engineering. LDM could also be combined with multinozzle deposition or cell deposition to exactly control materials or cells point by point. This might bring a breakthrough to the engineered fabrication of complicated organs.

Human vascular smooth muscle cells and endothelial cells cocultured on polyglycolic acid (70/30) scaffold in tissue engineered vascular graft.

BACKGROUND: Current prosthetic, small diameter vascular grafts showing poor long term patency rates have led to the pursuit of other biological materials. Biomaterials that successfully integrate into surrounding tissue should match not only the mechanical properties of tissues, but also topography. Polyglycolic acid (70/30) has been used as synthetic grafts to determine whether human vascular smooth muscle cells and endothelial cells attach, survive and secrete endothelin and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha). METHODS: Endothelial cells and smooth muscle cells were isolated from adult human great saphenous vein. They were seeded on polyglycolic acid scaffold in vitro separately to grow vascular patch (Groups A and B respectively) and cocultured in vitro to grow into vascular patch (Group C). Smooth muscle cells and endothelial cells were identified by immunohistochemical analysis and growth of cells on polyglycolic acid was investigated using scanning electron microscopy. The levels of endothelin and 6-keto-PGF1alpha in the culturing solutions were examined by radioimmunology to measure endothelial function. RESULTS: Seed smooth muscle cells adhered to polyglycolic acid scaffold and over 28 days grew in the interstices to form a uniform cell distribution throughout the scaffold. Then seed endothelial cells formed a complete endothelial layer on the smooth muscle cells. The levels of endothelin and 6-keto-prostaglandin F1 alpha in the culturing solution were (234 +/- 29) pg/ml and (428 +/- 98) pg/ml respectively in Group C and (196 +/- 30) pg/ml and (346 +/- 120) pg/ml in Group B; both significantly higher than in Groups A and D (blank control group, all P < 0.05). CONCLUSIONS: Cells could be grown successfully on polyglycolic acid and retain functions of secretion. Our next step is to use human saphenous vein smooth muscle cells and endothelial cells to grow tubular vascular grafts in vitro.

[Research about schwann cells and PLGA implanted to rat transected spinal cord].

OBJECTIVE: To investigate the recovery of rat transected spinal cord injury after implantation of Schwann cells combined with poly (lactide-co-glycolide) (PLGA). METHODS: Schwann cells were expanded, co-cultured with PLGA for 9 days in vitro, and then analyzed with scanning electron microscope (SEM). Rat spinal cord at the level of T(9) was transected. Schwann cells labeled with BrdU and PLGA scaffold were implanted to injury site. After 1, 3, 6 months, BrdU/MBP immunohistochemistry double staining, semi-thin sections stained thionin and ultra-thin section were performed to investigate myelin renew. BBB open field locomotion, motor evoked potential (MEP), compound muscle action potential (CMAP) and somatosensory evoked potential (SEP) were recorded. RESULTS: Schwann cells grew well on PLGA under SEM. BrdU/MBP double positive cells would been seen, remyelination was thin and formed by Schwann cells at 6 months later under electron microscope (EM). BBB behavioral tests revealed no significant difference in recovery comparing with experiment group and control group. The results of MEP, CMAP and SEP showed no significant improvement in the conduction of spinal cord. CONCLUSIONS: There are the compatibility between Schwann cells and PLGA. Although remyelination was found in morphology, function conduction of spinal cord failed to be established.

[A pharmacodynamics study of an intravitreal amphotericin B drug delivery system for the treatment of experimental Aspergillus fumigatus endophthalmitis].

OBJECTIVE: To observe a new amphotericin B drug delivery system (AmB-DDS), and investigate the therapeutic effects of AmB-DDS on an experimental Aspergillus fumigatus endophthalmitis. METHODS: (1) In order to observe the effects of AmB-DDS, thirty-four New Zealand albino rabbits were intravitreal injected Aspergillus fumigatus suspension (10(3) colony forming unit, CFU) in applanation of vitreous body before therapy 48 hours. All models were randomly divided into five groups. Group A was the empty control group, treated nothing after Aspergillus fumigatus injection, group B was the empty DDS implantation combined with vitrectomy, no treatment after DDS implanted, group C: AmB 5 microg-injection combined with vitrectomy, the injection was repeated two week later, group D: 250 microg AmB-DDS intravitreal implantation combined with vitrectomy, Group E: 500 microg AmB-DDS intravitreal implantation combined with vitrectomy. Aqueous flare, cells, anterior vitreous cells and vitreous opacity were graded, and vitreous humor smear and culture were performed at different time points after operation in 8 weeks. Two months after operation, light microscopy was used histology evaluation. (2) To observe the release of AmB-DDS in Group H (6 eyes), 500 microg AmB-DDS were implanted in the eye of the rabbits after vitrectomy, vitreous humor was aspirated and the concentrations of amphotericin B were determined by high performance liquid chromatography (HPLC). RESULTS: The inflammation response was lower in groups C, D, E than groups A, B. There was no significant statistical difference between group A and group B (P > 0.05), but differences among C, D, E and groups A, B were significant (P < or = 0.005). The inflammation grade was lower in group E than group C (P < or = 0.005). There was significant statistical difference between the cure effect of group E and group D (chi(2) = 10.494, P = 0.003). All of vitreous humor smears was positive in 1.5 months after surgery, but the culture was only positive in group A, and B. Pathological examination indicated that normal structure was disappeared in the eyes with Aspergillus endophthalmitis. At the first day after surgery, AmB were observed by analysis of HPLC, there was sustained AmB release in the group of AmB-DDS application during the observation periods. CONCLUSIONS: The degradable AmB-DDS can effectively suppress the inflammation of the rabbit model of Aspergillus fumigatus endophthalmitis. As an alternative to the current routine therapy, it can be used for the treatment of Aspergillus fumigatus endophthalmitis.

Drug release kinetics from a drug-eluting stent with asymmetrical coat.

The aim of this study was to investigate the drug release profiles of biodegradable polymer sirolimus- or paclitaxel-eluting stents with asymmetrical coating (BPSES-A or BPPES-A) both in vitro and in vivo. In vitro, the drug release profile was characterized by measuring the drug concentration by HPLC over a time-course. In vivo, a porcine aorta stenting model was employed. The results showed that the drug release rates of BPSES-A and BPPES-A were slower, more stable and less burst releasing than those of conventionally coated stents (BPSES-C and BPPES-C respectively), both in vitro and in vivo. Based on the in vivo results, the sirolimus and paclitaxel content of the local coronary wall was maintained at a higher and more effective level with BPSES-A and BPPES-A than with BPSES-C and BPPES-C, respectively. The drug levels in peripheral tissue samples were below detection levels. These data demonstrated the effectiveness of both sirolimus and paclitaxel as stent coating agents, and revealed the favorable drug release kinetics and pharmacokinetics of asymmetrical coated stents compared with conventional coated stents.

Sustained intraocular rapamycin delivery effectively prevents high-risk corneal allograft rejection and neovascularization in rabbits.

PURPOSE: To evaluate the immunosuppressive and antiangiogenic activities of an intraocular rapamycin (RAPA) drug delivery system (DDS) in a rabbit model of high-risk penetrating keratoplasty. METHODS: Forty New Zealand White rabbits with corneal neovascularization underwent allograft cornea transplantation and were randomly divided into four groups: a control group, a glycolide-co-lactide-co-caprolactone copolymer (PGLC)-implanted group, a RAPA eye drop group, and a RAPA-PGLC DDS-implanted group. Graft survival, corneal neovascularization, and RAPA concentration in the aqueous humor were monitored for 90 days. Corneal grafts were also examined by in situ hybridization and immunohistochemistry for proinflammatory gene expression. RESULTS: In the control and PGLC groups, graft rejection occurred within 3 weeks of keratoplasty. In the RAPA eye drop and RAPA-PGLC groups, corneal rejection was significantly delayed, and neovascularization was markedly inhibited. Median graft survival times were 36 and >90 days in the eye drop and RAPA-PGLC groups, respectively. Mean RAPA concentrations in the aqueous humor were 10.7 ng/mL, 12.0 ng/mL, 9.2 ng/mL, and 7.0 ng/mL in the RAPA-PGLC group 2, 4, 8, and 12 weeks after surgery, respectively. By contrast, RAPA was undetectable in the aqueous humor in the eye drop group. High levels of IL-2R, MCP-1, TNF-alpha, and VEGF were detected in the corneal grafts of the control and PGLC groups but not in those of the RAPA-treated groups. CONCLUSIONS: RAPA-PGLC DDS and RAPA eye drops can significantly prolong the survival of allografts at high risk and inhibit corneal neovascularization. However, RAPA-PGLC DDS is far more effective than RAPA eye drops in preventing corneal graft rejection.