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[Preparation of sustained-release nitrendipine microspheres with a solid dispersed structure in liquid system].

AIM: To prepare the sustained-release nitrendipine microspheres with a solid dispersed structure in liquid system. METHODS: The sustained-release nitrendipine microspheres with a solid dispersed structure was prepared in liquid system by combining spherical crystallization technique and solvent deposition method in one step. The resultant microspheres were evaluated for the recovery, micromeritc properties, incorporation efficiency. The factors of effect on the formation and the release rate of microspheres were also investigated. RESULTS: The recovery of microspheres (280-900 microns) was more than 70% and the bulk density was around 0.7 kg.L-1. The incorporation efficiency always exceeded 95%. The formation of microspheres was mainly affected by the amount of bridging liquid and the emulsifying agents in poor solvent. The release rate of nitrendipine from the microspheres could be controlled as desired by adjusting the ratio of talc to Eudragit RS PO in the formulation. CONCLUSION: The presented method was suitable for preparing sustained-release microspheres of a water insoluble drug.

Delayed-Action Preparations↗

Experimental study on fluorescent microspheres as a tracer for sentinel node detection.

BACKGROUND: Common tracers for sentinel node navigation surgery are blue dye and technetium-99m-labelled colloids. However, in most esophageal or lung cancer patients, it is impossible to detect the sentinel node among mediastinal nodes by blue dye because of the anthracotic pigmentation of mediastinal nodes. The use of technetium-99m-labelled colloids requires a special facility, while a large hot-spot at the injection site prevents detection of the sentinel node around the primary lesion. To overcome these problems, we investigated the use of fluorescent microspheres (0.1-20 microm in diameter) as tracers in animals and detected fluorescence-positive nodes by a simple ultraviolet light irradiation method. MATERIALS AND METHODS: Two milliliters of fluorescent microspheres 0.1-20 microm in diameter diluted to 2.5% weight per volume was injected via the tail vein of 30 rats; systemic side-effects were examined. One milliliter of 1.0 microm-diameter microspheres dilution was injected on the backs of 30 rats; local side-effects were examined. A microsphere dilution (0.2 ml, 1.0 microm-diameter microspheres) was injected into the footpad of 18 rats; the lymphatic pathway and drainage were examined. Five milliliters of 1.0 microm-diameter fluorescent microspheres was injected endoscopically into the submucosa of the esophagus, stomach and small and large bowels of 6 domestic pigs, and 5 ml was injected into the subadventitia of the esophagus or subserosa of the stomach, and small and large bowels. Fluorescence-positive lymph ducts or nodes were carefully observed under ultraviolet light irradiation. RESULTS: No systemic side-effects were observed in rats. Only mild edema and a mild inflammatory reaction were observed on the backs of rats. Fluorescent microspheres 0.1, 0.5 and 1.0 microm in diameter were detected in lymph ducts or nodes of pigs within 1 hour after injection. CONCLUSION: Sentinel node navigation surgery with the use of fluorescent microspheres might be feasible and advantageous for patients with esophageal or lung cancer, especially in the mediastinum.

Animals↗

[Preparation of alginate-chitosan-poly (lactic-co-glycolic acid) composite microsphere and its regulation of protein release].

AIM: To elevate the encapsulation efficiency, decrease the burst release and improve the release of protein entrapped in poly (lactic-co-glycolic acid) (PLGA) microspheres. The bovine serum albumin (BSA) composite microspheres of alginate-chitosan-PLGA were prepared and the release characteristics of BSA from this composite microspheres were studied. METHODS: The much smaller calcium alginate microcapsules were first prepared by a modified emulsification method in an isopropyl alcohol-washed way and coated with chitosan, then the alginate-chitosan microcapsules were further entrapped in PLGA to form the composite microspheres. The protein concentration was determined using a BCA protein assay kit. The release profiles were changed with various formulation factors. RESULTS: The average diameter of the composite microcapsules was about 30 microm. Comparing with 60% to 70% of the conventional PLGA microspheres, the average encapsulation efficiency was more than 80%, and the burst releases in phosphate buffer solution of the composite microspheres decreased from 40% and 50% to 25% and further to 5% in saline solution. CONCLUSION: The novel composite microspheres were prepared, the drug encapsulation efficiency increased and the burst release decreased. The desired release profiles could be obtained by regulating the ratios of PLG and PLA in the composite microspheres.

Alginates↗

[Preparation of controlled release microsphere incorporating bFGF and its effect on Schwann cells].

To study the preparation method of bFGF microspheres and to investigate the bioactivities of bFGF, which were released from the bFGF microspheres, on the cultured schwann cells. bFGF was microcapsulated with the multiple emulsion encapsulative method using PLGA as coating material. Its morphology, particle size distribution, drug loading-embedding rate and in vitro release property were studied. The cultured schwann cells were grouped according to the different ingredients being added to the culture medium: bFGF group, bFGF-PLGA group. Then the number, the viability and the cell cycle of schwann cells were measured. The morphology and the particle size distribution of the bFGF-PLGA microspheres were even and good; the drug-loading and drug-embedding rate of microspheres were (27.18 x 10(-3)) % +/- (0.51 x 10(-3)) %, 66. 43% +/- 1.24%; the release property of microspheres in vitro was good and the overall release rate was 72. 47% in 11 days. The in vitro cellular study showed: 1, 2 days after plate culture, the cell number and cell viability of bFGF group was much better than that of bFGF-PLGA group; 3, 4 days after plate culture, the cell number and cell viability of bFGF group and bFGF-PLGA group were not different statistically; 6, 8 days after plate culture, the cell number and cell viability of bFGF-PLGA group was much better than that of bFGF group. Through the flow cytometry examination: 2 days after plate culture, the GJ/M+S percentage of bFGF group was higher than that of bFGF-PLGA group; 4, 8 days after plate culture, the G2/M+S percentage of bFGF-PLGA group was higher than that of bFGF group. So, it is practical to prepare the bFGF-PLGA microspheres with the multiple emulsion encapsulative method. bFGF-PLGA microspheres can preserve the bioactivities of bFGF effectively and promotes the proliferation of schwann cells in a long period because of the controlled release of bFGF from microspheres.

Cell Proliferation↗

[Preparation, release and immunogenicity evaluation of HBsAg-PLGA microspheres].

OBJECTIVE: To investigate microencapsulation technique, release of HBsAg-PLGA microspheres and degradation of the polymer in vitro, and the level of immune response after the single-dose HBsAg-PLGA microspheres subcutaneously injected (sc) to BALB/c mice. METHODS: HBsAg-PLGA microspheres were prepared by double emulsion microencapsulation technique with orthogonal experiments. The pharmaceutical characteristics of size and surface morphology, antigen loading efficiency, release of HBsAg-PLGA microspheres and degradation of the polymer in vitro, and the level of immune response after single sc of PLGA microspheres in BALB/c mice were investigated. RESULTS: The concentration of PVA was the significant factor affecting the particle size (P<0.05). The release of protein from the microspheres was controlled mainly by the bulk erosion of polymer matrix. When single sc of HBsAg-PLGA microspheres mixed with different formulations, the immunogenicity effect was comparable to that of the aluminium adjuvant vaccine. CONCLUSION: The single-dose HBsAg-PLGA microspheres mixture with different release behavior is a promising candidate for controlled delivery vaccine.

Animals↗

Preparation and characterization of PLGA microspheres containing a staphylokinase variant (K35R).

AIM: To produce poly (lactic-co-glycolic acid) (PLGA) microspheres, containing a staphylokinase variant (K35R, DGR) with reduced immunogenecity and antiplatelet aggregation activities, which allowed the preservation of protein stability during both particle processing and drug release. METHODS: DGR-loaded microspheres were fabricated using a double emulsion-solvent evaporation technique. The effects of preparative parameters, such as stirring rate, polymer concentration, and the excipients of both internal and external aqueous phase (W2), on DGR encapsulation efficiency and microsphere characteristics were investigated. In vitro and in vivo release of DGR were conducted and the cause for instability of DGR during release was also investigated. RESULTS: Moderate ultrasonic treatment of aqueous DGR/dichloromethane mixtures caused approximately. Eighty four per cent DGR denaturation. However, the activity recovery of DGR almost amounted to 100% when 2% polyvinyl alcohol (PVA) was addled into the aqueous phase. It was found that NaCl in the external water phase significantly increased DGR encapsulation efficiency. Furthermore, NaCl in the external water phase played a role in determining size and surface morphology of microsphere. In vitro release test showed a burst release of DGR from microspheres, followed by sustained release of 50% total activity over 15 days. In vivo experiments showed that DGR released from microspheres sustained 5 days. Denaturation of DGR within microspheres might be resulted from acidic microclimate. CONCLUSION: The stability of DGR was effectively protected during microencapsulation and a relatively high encapsulation efficiency of DGR was obtained. PLGA microspheres could be an effective carrier for DGR.

Animals↗

[Long-acting injectable microspheres of glucagon-like peptide-1].

AIM: To prepare glucagon-like peptide-1 (GLP-1) loaded long-acting injectable microspheres and to evaluate their in vitro release behavior as well as its pharmacodynamics. METHODS: GLP-1 loaded microspheres were prepared with poly (lactic-co-glycolic acid) (PLGA) as carrier materials by dowble emulsion (W/O/W) method. Physical and chemical characteristics of microspheres, such as mean diameter, morphology and drug loading were evaluated. The in vitro release behavior and its influencing factors were determined by HPLC, also the bioactivity of GLP-1 in the course of encapsulation process and in vitro release were evaluated by in vivo animal experiments. The effect of reducing plasma glucose about GLP-1 microspheres were evaluated on the diabetes mice. RESULTS: Microspheres with good shape and dispersive quality were prepared. The drug entrapment efficiency was more than 80%. The accumulated release in one month is up to 85% and the release equation is in accord with zero-class release model. The bioactivity of GLP-1 was conserved with glutin as inner water phase, but in the course of in vitro release, the specific activity of CLP-1 in the microspheres decreased a little. GLP-1 microspheres can decrease the plasma glucose significantly and the effect can go on for one month. CONCLUSION: GLP-1 can be encapsulated in injectable microspheres to yield one-month continuous release when using biodegradable polymers PLGA as carrier material, and this technique will have a favorable perspective in the near future.

Animals↗

The in vivo distribution of the 99mTc-labelled albumin and gelatin microspheres of a tuberculostatic agent, rifampicin.

The preparation of albumin and gelatin microspheres with a tuberculostatic agent, rifampicin, was studied, and its in vivo distribution was investigated by providing its accumulation in the target organ lungs. The purpose of the study is to improve the effectiveness by injecting the microspheres intravenously with much smaller doses than normally required with generalized systemic administration, whilst reducing the systemic side effects. The emulsion polymerization method is applied in microsphere preparation, and glutaraldehyde is employed for albumin and formaldehyde for gelatin microspheres as the cross-linking agents. Biodistribution was determined by intravenous administration of particles of 25 to 27 microns 99mTc-labelled microspheres to Swiss albino mice. The radioactivity of the lungs was compared with the radioactivity of the liver, spleen, kidney, stomach and heart at 10, 30 and 60 min, and 6 and 24 h post-injection. The percentage accumulated was higher in the lungs than in the other organs for both albumin and gelatin microspheres, whereas free rifampicin accumulated mainly in the liver. To support the data of the in vivo distribution studies, the microspheres were histopathologically investigated after the intravenous injection to Swiss albino mice. After the microscopic determination of the lungs and liver, the spherical microspheres were observed after 10,30 and 60 min, and 6 and 24 h post-injection.

Animals↗

Aggregation of microspheres in blood flow measurements.

The aggregation of NEN-TRAC radionuclide-labeled 15 microns resin microspheres was studied in vitro and in vivo. In vitro, the control group not agitated at all was compared with groups subjected to agitation with a Vortex Shaker or agitation with first a Vortex shaker and then a sonification bath. Loading the microspheres in a catheter made agitation unnecessary (5.6 +/- 1.7 aggregates/100 spheres and 2.3 +/- 0.5 microspheres/aggregate). Sonification increased aggregation when the solution was drawn into 1 cc syringes (13.7 +/- 2.6 aggregates/100 spheres and 2.8 +/- 1.2 microspheres/aggregate). In vivo less aggregates were observed. Loading the microspheres into PK 50 catheters and then injecting them into the left ventricle of the heart after agitation in a Vortex shaker for 1 min minimized aggregation (1.6 +/- 1.0 aggregates/100 spheres and 2.2 +/- 0.4 spheres/aggregate). Sonification increased both the number of aggregates and the number of spheres in each aggregate significantly (10.0 +/- 3.1 aggreates/100 spheres and 2.8 +/- 1.3 spheres/aggregate). Aggregates of 10 to 40 microspheres were occasionally observed. When the microspheres were injected into the aorta at the level of the diaphragm, one large aggregate (approximately 50 spheres) was seen. The handling of the microsphere solution is important to prevent aggregation and the treatment recommended by the manufacturer does not seem to be the optimal. Large aggregates, which are rare, might embolize the precapillary arteries. Small aggregates are more common and they might result in disproportionately fewer microspheres in vessels than their actual blood flow. This would make the microsphere method less reliable in blood flow measurements.

Animals↗

[Studies on streptomycin albumin microspheres for injection].

Streptomycin albumin microspheres were prepared by polymeric dispersing agents. Some physical properties including the size, distribution and surface state of the microspheres were determined. The results showed that the diameter of the microspheres ranged from 10 to 30 microns and the content was 20.3 +/- 0.5%. Drug release from the microspheres was performed by a dynamic dialysis system. Tissue distribution of streptomycin albumin microspheres in rats was studied by both fluorescein isothiocyanate and 125I labelled microspheres. The experiments revealed that the major part of the microspheres accumulated in the lung following intravenous injection. The effectiveness and side effects of the streptomycin in the microspheres remain to be determined.

Albumins↗

Pharmacokinetics and pharmacodynamics of a parenteral testosterone microsphere formulation in the male rat. Demonstration of dose dependence and controlled release.

This study examined the pharmacokinetics (the time course and pattern of testosterone release) and pharmacodynamics (effects on accessory sex organ weights, and serum LH and FSH levels) of a biodegradable testosterone microsphere formulation in the male rat. Two hundred seventy-five 55-day-old, sexually mature male rats underwent surgical orchiectomy or sham surgery and were divided into five groups as follows, to receive placebo or testosterone microsphere systems designed to release 25, 75, or 225 micrograms/day testosterone: group I: intact age-matched controls, sham operated, placebo microspheres; group II: surgically orchiectomized, placebo microspheres; group III: surgically orchiectomized, 25 micrograms/day testosterone microspheres; group IV: surgically orchiectomized, 75 micrograms/day testosterone microspheres; and group V: surgically orchiectomized, 225 micrograms/day testosterone microspheres. Serum testosterone levels were fairly uniform from day 2 to 85 without any significant trend. After day 100, serum testosterone levels gradually fell into the castrate range by day 196. There was a dose-dependent increase in serum testosterone levels in groups III, IV, and V over those seen in group II (castrated rats, placebo treated). Prostate and seminal vesicle weights were significantly lower in castrated animals treated with placebo or the 25-micrograms/day testosterone microsphere system (group III). Mean prostate and seminal vesicle weights in groups IV and V were not significantly different from those in intact controls (group I) in the first 85 days. After day 85-100, seminal vesicle and prostate weights declined gradually in groups III, IV, and V, approaching castrate range by day 196.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Development of new reverse micellar microencapsulation technique to load water-soluble drug into PLGA microspheres.

The objective of this study was to develop a new reverse micelle-based microencapsulation technique to load tetracycline hydrochloride into PLGA microspheres. To do so, a reverse micellar system was formulated to dissolve tetracycline hydrochloride and water in ethyl formate with the aid of cetyltrimethylammonium bromide. The resultant micellar solution was used to dissolve 0.3 to 0.75 g of PLGA, and microspheres were prepared following a modified solvent quenching technique. As a control experiment, the drug was encapsulated into PLGA microspheres via a conventional methylene chloride-based emulsion procedure. The microspheres were then characterized with regard to drug loading efficiency, their size distribution and morphology. The reverse micellar procedure led to the formation of free-flowing, spherical microspheres with the size mode of 88 microm. When PLGA microspheres were prepared following the conventional methylene chloride-based procedure, most of tetracycline hydrochloride leached to the aqueous external phase: A maximal loading efficiency observed our experimental conditions was below 5%. Their surfaces had numerous pores, while their internal architecture was honey-combed. In sharp contrast, the new reverse micellar encapsulation technique permitted the attainment of a maximal loading efficiency of 63.19 +/- 0.64%. Also, the microspheres had smooth and pore-free surfaces, and hollow cavities were absent from their internal matrices. The results of this study demonstrated that PLGA microspheres could be successfully prepared following the new reverse micellar encapsulation technique.

Capsules↗

Novel mucosal immunization with polysaccharide-protein conjugates entrapped in alginate microspheres.

A novel mucosal immunization was examined using biocompatible and biodegradable alginate microspheres containing a conjugate of polysaccharide antigen and cholera toxin B subunit (CTB). In order to prepare the alginate microspheres with diameters of less than 5 microm, a new diffusion-controlled interfacial gelation technique was developed. Also, in order to improve the mucosal immune response, a pneumococcal capsular polysaccharide type 19 (PS19) was conjugated to the CTB (PS19-CTB). This conjugate was subsequently encapsulated into the alginate microspheres. The loading content of PS19-CTB to the alginate microspheres was 60%. An in vitro sustained release pattern was observed with the antigen-loaded microspheres, showing 80% antigen release within one day. Mucosal and systemic immunities following oral immunization with the alginate microspheres were studied. Balb/c mice were immunized perorally three times at intervals of two weeks. Peroral immunization with 25 microg of PS19-CTB entrapped in the alginate microspheres evoked both the mucosal IgA and systemic IgM responses to PS19 in small intestine and in sera, respectively. The results suggest that both the mucosal and systemic antibody responses could be induced by oral administration of the PS19-CTB antigen entrapped in alginate microspheres.

Alginates↗

Interfacial synthesis of hollow TiO2 microspheres in ionic liquids.

An interfacial sol-gel synthesis of inorganic hollow microspheres in room-temperature ionic liquids is newly developed. When metal alkoxides such as titanium tetrabutoxide, Ti(OBu)4, are dissolved in anhydrous toluene and injected into 1-buthyl-3-methylimidazolium hexafluorophosphate ([C4mim]PF6) under vigorous stirring, hollow titania microspheres are formed. The present technique is widely applicable to the reactive metal alkoxides such as Zr(OBu)4, Hf(OBu)4, Nb(OBu)4, and InSn3(OR)x, giving a general route to the metal oxide microspheres. When gold nanoparicles and carboxylate-containing dyes such as fluorescein isothiocyanate (FITC) are dissolved in the toluene microdroplets, they are stably immobilized in the microsphere shells. Calcination of the titania gel microspheres gives anatase TiO2 microspheres. The present method provides the first example of inorganic hollow microspheres formed in ionic liquids, and the ability to modify microspheres with metal nanoparticles or functional organic molecules would be widely applied to the design of smart organic/inorganic hybrid materials.

Journal Article↗

In vitro protein release and degradation of poly-dl-lactide-poly(ethylene glycol) microspheres with entrapped human serum albumin: quantitative evaluation of the factors involved in protein release phases.

PURPOSE: To quantitatively evaluate the correlations between the amount of initial burst release and the surface-associated protein, and between the onset time for the second burst release and the matrix polymer degradation. METHODS: Human serum albumin (HSA) was microencapsulated in polylactide (PLA) and poly-dl-lactide-poly(ethylene glycol) (PELA) with PEG contents of 5, 10, 20, and 30%, respectively, using the solvent extraction procedure based on formation of double emulsion w/o/w. Microspheres with similar particle size (1.7-2.0 microm), similar protein entrapment (2.1-2.8%) but different surface-associated proteins (9.3-53.6%) were used to evaluate the in vitro matrix degradation and protein release profiles. Degradation was characterized by studying the intrinsic viscosity decrease, medium pH change, and weight loss of the microspheres. RESULTS: The matrix degradation and protein release profiles were highly dependent on the polymer composition of the microspheres. Faster decreases in the intrinsic viscosity of recovered matrix polymer, the microspheres weight, and the pH of degradation medium, and earlier onsets for the break in intrinsic viscosity reduction and the mass loss were detected for PELA microspheres with higher PEG content. The hydration and swelling of microspheres matrix contributed greatly to the degradation of matrix polymer. The HSA release showed triphasic profile and involved two mechanisms for all the microsphere samples. Smaller amount of initial burst release, larger gradual release rate, and earlier onset for the second burst release were observed for HSA from matrix polymer with higher PEG content. The extent of the initial burst release was quantitatively related with the surface-associated protein. The second burst release of HSA was observed to occur within 1 week after the onset for mass loss, which was also the break in the intrinsic viscosity reduction rate. CONCLUSION: Protein release profiles could be rationalized by optimizing the matrix polymer degradation and microsphere characteristics.

Biocompatible Materials↗

pH dependent hydrolysis and drug release behavior of chitosan/poly(ethylene glycol) polymer network microspheres.

Semi-interpenetrating polymer network (IPN) microspheres of chitosan and poly(ethylene glycol) PEG were prepared for controlled release of drugs. A new method for the chemical crosslinking of chitosan microspheres containing isoniazid (INH) as a model drug is proposed and evaluated. The method consists of the exposure of microspheres to the vapor of crosslinking agent that act in gaseous phase under mild conditions. The structural analysis of the microspheres was carried out by FTIR-analysis. The swelling behavior, hydrolytic degradation, structural changes of the microspheres and loading capacity (LC) of the microspheres for INH were investigated. The prepared microspheres have shown 93% drug loading capacity, which suggested that these semi-IPN microspheres are suitable for controlled release of drugs in an oral sustained delivery system.

Journal Article↗

Colchicine encapsulation within poly(ethylene glycol)-coated poly(lactic acid)/poly(epsilon-caprolactone) microspheres-controlled release studies.

Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Local delivery of agents capable of modulating vascular responses have the potential to prevent restenosis. However, the development of injectable microspheres for maintaining high tissue levels of drugs at the site of vascular injury is a major challenge. We demonstrated the possibility of entrapping an antiproliferative agent, colchicine, in polyethylene glycol (PEG)-coated biodegradable microspheres composed of poly(lactic acid)/poly(epsilon-caprolactone) blends, with a mean diameter of 3-6 microm. A solution of colchicine and blends of polylactic acid (PLA)/polycaprolactone (PCL) dissolved in acetone-dichloromethane mixture was poured into an aqueous solution of PEG (or polyvinyl alcohol) with stirring by a high-speed homogenizer to form microspheres. Colchicine recovery in microspheres ranged from 30-50% depending on the emulsification system and the ratio of polymer blends used for the preparations. Scanning electron microscopy revealed that the PLA/PCL microspheres were spherical in shape and had a smooth surface texture. Results of in vitro release studies showed that it is possible to control the colchicine release by choosing the appropriate particle size, loading, and PLA/PCL composition. Water permeability through the PLA membrane was greater, when compared with PCL blends. The amount of drug release also was much higher (58.3%) in PLA compared with PCL (39.3%) microspheres, for 30 days. Therefore, we concluded that the drug release from the microspheres followed a diffusion mechanism where bulk erosion and surface deposition were negligible. These PEG-coated PLA/PCL microspheres may have potential for targeting antiproliferative agents for prolonged periods to treat restenosis.

Caproates↗

Incorporation of nitric oxide-releasing crosslinked polyethyleneimine microspheres into vascular grafts.

Over the years, many attempts have been made to increase the patency of small- to medium-sized prosthetic vascular grafts. However, none of them has greatly affected long-term rates. Recently, nitric oxide (NO) has been shown to inhibit thrombus formation in such grafts, suggesting that local delivery of NO may help to increase graft patency. This study describes the site-specific delivery of NO by entrapping NO-releasing microspheres in the pores of a vascular graft. NO-releasing polyethyleneimine microspheres (PEIX) were developed using a novel water-in-oil emulsion technique involving chemical crosslinking with a bis-epoxide. The PEIX microspheres were then derivatized with NO forming the [N(O)NO]- moiety of the diazeniumdiolates formerly known as NONOates. These polymeric NO-releasing particles were found to spontaneously release 194 nmol NO/mg with a half-life of over 66 h under physiologic conditions. Fluorescein isothiocyanate-labeled microspheres were then embedded into the pores of a 60-micron nonreinforced Gore-tex vascular graft using a simple evacuation technique and evaluated for microsphere placement and NO release. Scanning electron microscopic analysis showed the microspheres entrapped in the pores of the vascular graft releasing 10 nmol NO/mg with a half-life of 51 h. The microspheres remained entrapped in the graft even after immersion and NO release, as confirmed by fluorescence of the medium. These results suggest that NO-releasing particles can be incorporated into the pores of a vascular graft to deliver therapeutic amounts of NO for the prevention of thrombosis in small-diameter prosthetic grafts.

Blood Vessel Prosthesis↗