介孔二氧化硅微球的制备及用于吲哚美辛载药与溶出性质

目的制备介孔二氧化硅微球,以期提高吲哚美辛的溶出速率。方法以表面活性剂十六烷基三甲基溴化铵和普兰尼克三嵌段共聚物P123作为双模板,用软膜板法制备具有介孔孔道的介孔二氧化硅微球药物载体,采用扫描电镜及氮气吸附-脱附手段表征载体形貌、比表面积及孔径分布。用吸附平衡挥干法载药制得吲哚美辛固体分散体,并对该固体分散体的溶出性质进行研究。结果制得的介孔二氧化硅载体由粒径相对均一的球形粒子组成。其粒径主要集中在2～5μm,载体的比表面积为502.87 m²·g2·g^(-1),孔容为2.23 cm(-1),孔容为2.23 cm³·g3·g^(-1),孔径为23.75 nm。吲哚美辛/介孔二氧化硅固体分散体的药物溶出速率与累积溶出度与吲哚美辛原料药相比均有了显著提高。结论吲哚美辛已高度分散于微球载体中,药物的溶出速率明显加快,为提高吲哚美辛生物利用度的研究打下了基础。     

Distribution of coronary blood flow during acute coronary occlusion in dogs. Effect of nicotinic acid and sodium salicylate

The effects of the antilipolytic agents nicotinic acid (NA) and sodium salicylate (SS) on the distribution of coronary blood flow during acute myocardial ischaemia were studied in open chest dogs. Fifteen min following experimental coronary artery occlusion, blood flow in the ischaemic myocardium was on average 28% of flow in the non-ischaemic myocardium. The reduction in blood flow in the ischaemic mycardium was more pronounced in the endocardial than in epicardial halves of the myocardium. No significant change in blood flow was observed after administration of NA or SS in either the ischemic or nonischemic part of the myocardium. Both drugs reduced the extent of myocardial ischaemic injury as shown by reduced epicardial ST-segment elevations. Arterial concentrations of fatty acids were lowered by NA or SS, whereas the mechanical activity of the heart remained unchanged. It is concluded that the reduction of acute myocardial ischaemic injury effected by NA or SS is not due to changes in myocardial blood flow, but more likely to lower myocardial oxygen demand related to reduced fatty acid utilization.     

Preparation and characterization of Vitamin-12 loaded biodegradable pH-sensitive microgels

This paper prepared novel biodegradable and pH-sensitive microgels based on Poly(ε-caprolactone)-Pluronic-Poly(ε-caprolactone)-dimethacrylate (PCFC-DMA), Poly(ethylene glycol) dimethacrylate (PEG-DMA) and methylacrylic acid (MAA) cross-linked with N,N’-methylenebisacrylamide (BIS), initiated by NaHSO₃, K₂S₂O₈. The blank microgels were prepared by inversed-phase suspension polymerization method and pH sensitivity of microgels was characterized. Then the blank microgels were loaded with hydrophilic model drug vitamin-12 (VB-12) and in vitro drug release behaviour was also studied here.     

Preparation and in-vitro evaluation of sustained-release metoclopramide hydrochloride microspheres

Abstract

Sustained-release metoclopramide microspheres were successfully prepared using cellulose propionate polymer at 1:2 drug to polymer ratio employing solvent evaporation technique and using acetone as the polymer solvent. The prepared microspheres at three stirring speeds were characterized with regard to their drug content, particle size distribution, surface topography using SEM and their release profiles at two different pHs at 37°C. The surface of all samples was smooth with very few irregular elevations or depressions. The average particle size decreases as the rotational speed increases and was found to be 1320, 774 and 345 μm at 600, 900 and 1200rpm, respectively. The average % drug entrapped was found to be 90.5, 100.1 and 60.0% at 600, 900 and 1200 rpm, respectively. Small differences in the release rate were observed due to different rotation speeds with an apparent lower dissolution for batches produced at 1200 rpm probably due to the properties of the coat. The effect of storage under accelerated conditions for 10 weeks on the release characteristics of these microspheres was also studied. The release properties of the microspheres did not change after storing them at 40°C/80% relative humidity for 10 weeks.     

Development of biodegradable drug releasing polymeric cardiovascular stents and in vitro evaluation

Prednisolone acetate (PA) is insoluble in water and was chosen as a model drug for its anti-inflammatory/anti-proliferative functions. PA is incorporated into the film-based polymeric biodegradable stents to provide controlled local release of the drug during the mechanical support phase. Stent formulations were 3 mm in diameter with lengths of 150 mm. The polymer wall thickness was 145.0 ± 4.0 µm for microsphere-containing PLGA 75 : 25 stents. The ATR-FTIR spectra showed biodegradable stent surfaces were free of drug and microspheres. Incorporation of PA into the stents increased the surface area when compared to empty and microsphere-incorporated stents. PA release from the stents containing chitosan microspheres was slower than the PA-only incorporated stents. The drug release from the stents coated with microsphere-containing PLGA 75 : 25 solutions was determined to be the slowest one (19.1% cumulative PA released in 32 days). The stents formulated with PLGA 75 : 25 polymers were considered to be more promising due to their suitable mechanical properties and controlled release of the drug.     

Tabletted microspheres containing Cynara scolymus (var. Spinoso sardo) extract for the preparation of controlled release nutraceutical matrices

Controlled release dosage forms based on tabletted microspheres containing fresh artichoke Cynara scolymus extract were performed for the oral administration of a nutritional supplement. Microspheres were prepared using a spray-drying technique; lactose or hypromellose have been chosen as excipients. Microspheres were characterized in terms of encapsulated extract content, size and morphology. Qualitative and quantitative composition of the extract before and after the spray process was determined. Compressed matrices (tablets) were prepared by direct compression of the spray-dried microspheres. In vitro release tests of microparticles and tablets prepared were carried out in both acidic and neutral media. Spray-drying is a good method to prepare microspheres containing the artichoke extract. The microspheres encapsulate an amount of extract close to the theoretical value. Particle size analyses indicate that the microparticles have dvs of ～6–7?µm. Electronic microscopy observations reveal that particles based on lactose have spherical shape and particles containing hypromellose are almost collapsed. The hydroalcoholic extract is stable to the microsphere production process: its polyphenolic composition (qualitative and quantitative) did not change after spraying. In vitro release studies show that microparticles characterized by a quick polyphenolic release both in acidic and neutral media due to the high water solubility of the carrier lactose. On the contrary, microspheres based hypromellose release only 20% of the loaded extract at pH 1.2 in 2?h and the total amount of polyphenols is released only after about further 6?h at pH 6.8. Matrices prepared tabletting lactose microspheres and hypromellose microparticles in the weight ratio 1:1 show a slow release rate, that lasts ～24?h. This one-a-day sustained release formulation containing Cynara scolymus extract could be proposed as a nutraceutical controlled release dosage form for oral administration.     

In vitro and in vivo properties of usnic acid encapsulated into PLGA-microspheres

Microparticles will probably play a promising role in the future of chemotherapy. These polymeric delivery systems are capable of maximizing the therapeutic activity while reducing side effects of anti-cancer agents. Usnic acid (UA) is a secondary metabolite produced by lichens, which exhibits an anti-tumour activity. In this study, PLGA-microspheres containing usnic acid from Cladonia substellata were prepared by the double emulsion method, with or without PEG as stabilizer. The morphology of the microspheres was examined by optical and scanning electron microscopy. The in vitro kinetic profile of usnic acid loaded-microspheres was carried out by dissolution testing. The usnic acid content was analysed by HPLC. The cytotoxicity of free and encapsulated usnic acid was evaluated against HEp-2 cells using the MTT method. The anti-tumour assay was performed in mice against Sarcoma-180 tumour (UA 15?mg?kg^?1 weight body/day) during 7 days. Animals were then sacrificed and tumour and organs were excised for histopathological analysis. Microspheres presented a smooth spherical surface with a mean diameter of 7.02?±?2.72?µm. The usnic acid encapsulation efficiency was ～100% (UA 10?mg 460?mg^?1 microspheres). A maximum release of 92% was achieved at the fifth day. The IC₅₀ values for free and encapsulated usnic acid were 12 and 14?µg?ml^?1, respectively. The encapsulation of usnic acid into microspheres promoted an increase of 21% in the tumour inhibition as compared with the free usnic acid treatment. In summary, usnic acid was efficiently encapsulated into PLGA-microspheres and the microencapsulation improved its anti-tumour activity.     

Encapsulation and release characteristics of DCTN/PLGA microspheres

In the present study, poly (D,L-lactic-co-glycolic)-acid microspheres containing trans-Dehydrocrotonin (DCTN) were prepared by the double emulsion method. The hypoglycemic activity of DCTN-loaded microspheres was monitored in normal glycemic mice after administration of a daily dose of DCTN (50 mg kg^?1 body weight) for 7 days. Spherical microspheres with two populations of particles with 3.20 ± 0.10 and 7.60 ± 0.70 µm mean diameter size µm were observed. The encapsulation efficiency of DCTN was 85.5 ± 3.9%. The in vitro kinetic profile of DCTN from PLGA-microspheres was initially fast (burst effect of 19.4% at 2 h). Such a burst step was maintained until achieving 35.7±2.0% at 7h, followed by a gradual release of DCTN attaining a maximum drug release at 55.7 ± 2.6% within 30 h. DCTN was able to reduce glucose levels (14.3%) of normal glycemic animals and this effect was improved by its encapsulation into microspheres (26.8%). The optimum glucose levels in the blood of animals treated with DCTN suspension and DCTN-loaded microspheres were 119.21 ± 19.75 mg dL^?1 at day 5 and 103.08 ± 18.88 mg dL^?1 at day 7, respectively. DCTN-loaded microspheres are thus offered as a potential delivery system for the treatment of metabolic diseases characterized by hyperglycemia.     

An approach to the design of a particulate system for oral protein delivery. I. In vitro stability of various poly (α-hydroxy acids)-microspheres in simulated gastrointestinal fluids

The stability of various biodegradable polyester polymers with different molecular weights and lactic/glycolic acids ratios were evaluated in simulated gastrointestinal fluids as an approach to apply microparticles for oral protein delivery on the basis of particle uptake mechanism. A common w/o/w emulsion solvent evaporation technique using dichloromethane for dissolving the polymer and polyvinyl alcohol as the stabilizer was used for encapsulation. Microspheres were incubated at 37°C in USP simulated fluids with a concentration of 20 mg mL^?1 and also in the literature, which suggested fed or fasted simulated intestinal fluids for different times up to 24 h, while shaking at 75 rpm. The stability assessment was done by detecting pH alterations of the media, enzymatic assay of L-lactic acid, performing differential scanning calorimetric studies and observing the size and morphology of particles. Results showed that the three polymers, namely Resomers® R207, RG756 and RG505, could be suitable for the preparation of protein-loaded microspheres.     

A Novel Resorbable Embolization Microsphere for Transient Uterine Artery Occlusion: A Comparative Study with Trisacryl-Gelatin Microspheres in the Sheep Model

PurposeTo evaluate angiographic recanalization, inflammatory reaction, and uterine damage after sheep uterine artery embolization (UAE) with a novel calibrated resorbable embolization microsphere (REM) and compare the results with control nonresorbable microspheres.Materials and MethodsSix hormonally artificially cycled sheep underwent bilateral UAE until stasis with either REM or trisacryl-gelatin microspheres (TGMS). At 7 days, control angiograms were obtained to assess the residual vascularization at arterial and parenchymal phases. The animals were then sacrificed for analysis of the presence of microspheres, inflammatory foreign body reaction, and surface areas of uterine damage.ResultsMean volume of microspheres injected per uterine artery (UA) or per animal did not differ between groups. At day 7, the flow was normal for six of six UAs that received embolization with REM versus only three of six UAs with TGMS (P = .0455, χ² test). Uterine parenchymography showed no defects in six UAs in the REM group versus five defects in six UAs in the TGMS group (P = .0060, χ² test). No REM or residual fragments of microspheres were observed on histologic analysis. TGMS were observed in tissues and accompanied by a mild inflammatory response. Necrosis rates were not significantly different between the two products, either in endometrium (REM 23.5% ± 28.8% [median 8.1%] vs TGMS 21.8% ± 23.7% [median 14.6%]) or in myometrium (REM 8.2% ± 22.7% [median 0.0%] vs TGMS 8.8% ± 20.8% [median 0.9%]). Endometrium alteration rate was lower with REM than with TGMS (39.7% ± 25.7% [median 34%] vs 60.6% ± 27.1% [median 71%]; P = .0060, Mann-Whitney test). Myometrium alteration rates were not significantly different between REM (45.7% ± 37.1% [median 63.0%]) and TGMS (37.8% ± 34.0% [median 19.1%]).ConclusionsAt 1 week after sheep UAE with REM, the recanalization was complete, the microspheres were completely degraded, and there was no remnant inflammatory response.