Microspheres of essential oil in polylactic acid and poly(methyl methacrylate) matrices and their blends

This study is focussed on micro-encapsulation of essential oils in polylactic acid (PLA) and a poly(methyl methacrylate) (PMMA) matrix as well as blends of the same. Microspheres were prepared by the solvent evaporation technique and characterised by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infra-red spectroscopy (FTIR). The encapsulation efficiencies and release profiles of the essential oils were studied by gas chromatography mass spectrometry (GC-MS) and head-space solid-phase microextraction GC-MS, respectively. Furthermore, the microspheres were tested for antibacterial activity against both Gram-negative and Gram-positive bacterial strains.

The results showed that the microspheres compositions (PLA/PMMA ratio) have significant effect on their characteristics. The process adopted for preparing the microspheres promoted formation of spherical particles at the sizes of 1.5–9.5?µm. The highest encapsulation efficiency of the prepared microspheres was observed in systems consisting of linalool (81.10?±?10.0?wt. % for PLA system and 76.0?±?3.3?wt. % for PMMA system). Confirmation was also made that the release rate of the microspheres was affected by the size of the same.     

Indomethacin-Dipalmitoylphosphatidylcholine Interaction. A Calorimetric Study of Drug Release from Poly(Lactide-co-glycolide) Microspheres into Multilamellar Vesicles

A comparative study of indomethacin controlled release from poly(lactide-co-glycolide) (50:50, molecular weight 3000) (PLGA) microspheres loaded with two different amounts of drug (10.9 ± 1%, and 34.1 ± 1% w/w) and pure free indomethacin, considering the effects exerted by the drug on the thermotropic behavior of dipalmitoylphosphatidylcholine multilamellar vesicles, was carried out by differential scanning calorimetry (DSC). The release was monitored by comparing the effect exerted by the free indomethacin on lipid thermotropic behavior with that of the drug released by the microspheres and relating these effects to a lipid aqueous dispersion containing the molar ratio of drug able to cause it. By DSC measurements, the pure free indomethacin was found to be able to have a fluidifying effect on the model membrane, causing a shift toward lower values of the transitional temperature (T_m), characteristic of phospholipid liposomes, without variations in the enthalpic changes (ΔH). This shift was found to be modulated by the drug molar fraction with respect to the lipid concentration in the aqueous dispersion. Successively, calorimetric measurements were performed on suspensions of blank liposomes added to weighed amounts of unloaded and indometha-cin-loaded microspheres as well as free powdered indomethacin, and the T_m shifts of the lipid bilayer caused by the drug released from the polymeric system, as well as by the free drug, were compared with that caused by free drug increasing molar fractions dispersed directly on the membrane, employed as a calibration curve to obtain the fraction of drug released. This drug release model could be employed to determine the different kinetics involved in the drug transfer from the microspheres to a membrane. This in vitro study suggests that the kinetic process involved in drug release is influenced by the amount of drug loaded in the microspheres. This calorimetric study shows that the PLGA microspheres are a good delivery system able to sustain drug release. Moreover, the DSC technique applied to the drug interaction with biomembranes constitutes a good tool for determining the drug release representing an innovative alternative in vitro model.     

Influence of Size, Dosage, and Surface Structure on Clearance and Tissue Distribution of Intravenous Microspheres

Intravenously injected polystyrene microspheres with functional amino groups (AP-MSs, 0.2,1.0, and 4.0 urn in diameter) were cleared from the blood very rapidly. The calculated half-lives for 0.2-, 1.0-, and 4.0-μm AP-MSs were about 55,60, and 50s; no significant differences were found with 10⁶,10⁷, and 10⁸ microspheres/rat. Loading experiments showed that the liver, spleen, lung, kidney, and heart had a very high capacity to take up AP-MSs. The AP-MSs were distributed mainly to the liver, lung, and spleen, whereas other organs contained less than 1 % of injected AP-MSs. In terms of numbers of AP-MSs per gram of tissue, the highest contents were found in spleen, liver, and lung for 0.2-, 1.0-, and 4.0-um AP-MSs, respectively. There was indication of redistribution of particles from one organ to another during the first 6 h after injection. Chondroitin sulfate A (Chon) and hyaluronic acid (Hya) adsorbed or covalently linked to AP-MSs increased uptake in the liver, with Chon AP-MSs (adsorbed or linked) showing the best effect: about 25% increase compared with unadsorbed 1-μm AP-MSs. Experiments with separated cells in vitro demonstrated that 1 um AP-MSs, intravenously injected, associated only with Kupffer cells. When the microspheres were adsorbed with Chon, there was also association with liver endothelial cells. This finding indicates that conjugation of microspheres with ligands for endothelial receptors may be a useful method for directing microspheres to specific organs, even if the receptors are not by themselves phagocytic     

明胶-聚乳酸载药纳米微球的制备及其体外释药研究

采用复合乳液—溶剂挥发法制得明胶—聚乳酸载五氟脲嘧啶(5—Fu)微球，以混合型乳化剂Tween—80：Span—80＝5：1—作为初乳乳化剂，O—羧甲基壳聚糖作为复乳乳化剂，考察了明胶—聚乳酸载药微球的制备条件对微球的成球性、药物包封率及体外释药的影响。结果表明乳化剂的选择、内部水相药物浓度和PLA分子量等均对载药微球的结构与性能产生影响，经优化条件得到了成球性和体外释放都比较好的载药微球。     

羧甲基壳聚糖作为植入可降解缓释微球辅料的实验研究

羧甲基壳聚糖作为一种高分子材料 ,具有良好的组织相容性和生物可降解性。本实验试图利用羧甲基壳聚糖作为植入环丙沙星微球的缓释辅料 ,并探索这一剂型的制备工艺、结构形态和体外释药特性。首先我们采用乳化交联技术制备微球 ;然后用扫描电子显微镜、红外光谱、及示差热分析等方法研究微球的结构和形态 ;建立体外持续流动释放系统初步检测微球的体外释放特性。实验结果发现 :微球的结构和形态受制备工艺条件如温度、离子强度、搅拌速度等因素的影响 ;一定工艺条件下制备的环丙沙星微球的体外释放时间可达 7d以上 ,释放行为符合 Higuchi方程。因此 ,我们认为 :羧甲基壳聚糖可作为环丙沙星可降解植入微球的缓释辅料 ;乳化交联技术是制备这一微球的有效方法 ,工艺简单、稳定     

Distribution of cardiac output in different models of hypertension in the conscious rat

The distribution of cardiac output was determined by 15 m radioactive microspheres in all the major organs of spontaneous, DOCA/NaCl and one kidney Goldblatt hypertensive rats and compared to normotensive Wistar rats. Although there were alterations in cardiac output distribution which were characteristic of each model of hypertension significant changes were common to all three were an increased distribution to skeletal muscle with decreases to the lungs, spleen and hepatosplanchnic tissues. The results suggest that alterations in peripheral resistance induced by hypertension are of unequal importance in the different vascular beds with certain vascular resistance changes occurring irrespective of the origin of the hypertension.Abbreviations used in this paper SHR spontaneously hypertensive rats - DOCA deoxycorticosterone acetate Supported by I.C.I. Pharmaceutical Ldt and the Mersey Regional Health Authority (Research Schemes No. 338).     

Effects of EGF and bFGF on Irradiated Parotid Glands

Radiotherapy is common treatment for head-and-neck cancer, during which the salivary glands are often included within the radiation field. The most common side effect of this treatment is the development of oral dryness (xerostomia). This study considers the administration of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF or FGF2) at physiological concentrations before and after irradiation in order to repair radiation-induced damage in salivary gland cells. As a preliminary examination of the efficacy of this approach we have characterized the effects of EGF and bFGF on the apoptotic response of 15-Gy irradiated rat salivary glands in vitro. Also, we have developed a controlled-release delivery system to effectively administer the growth factor to the gland since local delivery is essential to avoid unwanted protection of cancer cells. In vitro administration of bFGF prior to and immediately after irradiation partially protected (44%) the rat parotid gland. EGF did not show any significant radioprotective effect on parotid glands after a single 15-Gy irradiation dose. Encapsulation, storage and release of bFGF from biodegradable 50/50 PLGA microspheres did not affect the functionality of the growth factor in vitro.     

Experimentelle Bedingungen zur Reproduktion eines submucösen Steal-Phänomens am Hundemagen

Zusammenfassung Der Einfluß von Pentagastrin auf die Durchblutung des Hundemagens wurde mit 9-Mikrosphären untersucht. Schon 6 min nach dem Beginn der Pentagastrin-Infusion nimmt bei nüchternen Tieren der Fluß in allen Magenarealen zu. Mißt man die Änderung der Durchblutung zwei Stunden postprandial, so findet sich ein Durchblutungsanstieg lediglich im Bereich der Corpusmucosa, während die Antrummucosadurchblutung unter den Ausgangswert abfällt. Dieses intragastrale Steal-Phänomen findet auf der Ebene des submucösen Plexus statt.

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Experimental conditions for the reproduction of a submucous steal-phenomenon in the dog stomach

Summary The influence of pentagastrin on gastric blood flow has been investigated using 9-microspheres in dogs. As soon as 6 min after the onset of a pentagastrin infusion blood flow rises in all gastric probes in fasted animals. In dogs, fed two hours previously, such a response can only be seen in the corpus-mucosa areas. Blood flow in the antrum mucosa specimen falls beneath its initial value. This gastric steal-phenomenon takes place at the level of the submucous plexus, as has been shown earlier.

     

生物降解型尼索地平微球的研究

目的制备尼索地平的PLGA微球,并研究其体内外释药行为.方法采用溶剂挥发法制备微球,电镜下观察微球形态,HPLC法测定微球的载药量、包封率及累积释药量.采用HPLC法测定家兔体内的血药浓度.结果微球形态圆整,表面光滑.微球的粒径为15.3±3.8μm,载药量为21.16%,包封率为85.40%.微球的体外释药行为的拟合方程为1-Q=0.7654(1-t/t     

The in-vitro and in-vivo characterization of PLGA:L-PLA microspheres containing dexamethasone sodium phosphate

Dexamethasone sodium phosphate (DSP) is a widely used corticosteroid in the treatment of brain oedema associated with brain tumours. DSP has many side effects that limit its usage at an effective concentration. The objective of this study was to minimize these side effects by encapsulating DSP using biodegradable synthetic polymers, to extend the release time from microspheres and to evaluate the effectiveness in the treatment of brain oedema. Microspheres containing 5% DSP were formulated by the solvent evaporation method by using a 1:1 mixture of two synthetic polymers, poly(lactic-co-glycolic acid) and L-polylactic acid (PLGA and L-PLA). The surface morphologies and particle size distribution of the microspheres were investigated. The in-vitro