醋酸亮丙瑞林脂质体及壳聚糖包衣脂质体经肠道及Caco-2细胞转运机制

目的考察醋酸亮丙瑞林脂质体及壳聚糖包衣脂质体经大鼠肠道及Caco-2细胞的转运机制。方法应用翻转肠囊法和Caco-2 细胞模型考察游离醋酸亮丙瑞林、脂质体包封的醋酸亮丙瑞林以及壳聚糖包衣脂质体中醋酸亮丙瑞林的转运特征。在Caco-2细胞水平考察壳聚糖浓度、加入次序对脂质体中醋酸亮丙瑞林渗透的影响。结果游离醋酸亮丙瑞林的转运符合被动扩散的性质。相同实验条件下，脂质体中药物渗透量低于游离药物。可能是由于脂质体包封醋酸亮丙瑞林，阻止了药物向肠囊和Caco-2细胞转运。但是脂质体对酶降解醋酸亮丙瑞林具有保护作用。壳聚糖促进脂质体中亮丙瑞林的转运，壳聚糖的促渗作用在0.1%-0.5%浓度范围无明显差异。壳聚糖包覆脂质体后的促渗作用弱于其单独使用的促渗作用。结论壳聚糖包衣醋酸亮丙瑞林脂质体兼有保护和促渗作用，可能促进醋酸亮丙瑞林的口服吸收。     

Preparation,Optimization and Characterization of Bovine Lactoferrin‐loaded Liposomes and Solid Lipid Particles Modified by Hydrophilic Polymers Using Factorial Design

Bioadhesive liposomes and solid lipid particles (SLPs) modified by pectin and chitosan for oral administration of bovine lactoferrin (bLf) were prepared using a 2⁴ full‐factorial design to identify the key formulation variables influencing particle size and drug entrapment efficiency (EE). Netlike structures of the polymer–particle mixture consisting of a polymeric network in which multiple particles were imbedded were observed by scanning electron microscopy (SEM). Chemical stability of bLf after encapsulation into pectin‐ and chitosan‐modified liposomes and SLPs was confirmed by Fourier transform infrared spectra (FTIR). Bovine lactoferrin was located within phospholipid bilayer, whereas in SLPs bLf was within the matrix. The crystalline nature of bLf after encapsulation was investigated by differential scanning calorimetry (DSC) of drug‐loaded particles, indicating amorphous dispersion of bLf in the polymer–lipid matrix of pectin‐ and chitosan‐modified liposomes and SLPs. In vivo pharmacokinetic investigation of bLf in pectin‐ and chitosan‐modified liposomes and SLPs showed prolonged mean residence time (MRT) of bLf in rat blood and increased the relative bioavailability (F_bio%) by 1.95‐ to 2.69‐fold compared with free bLf. The developed carrier systems are considered to be promising vehicles for oral delivery.     

Liposomes encapsulating prednisolone and prednisolone-cyclodextrin complexes: comparison of membrane integrity and drug release.

Inclusion complexes of prednisolone (PR) with beta-cyclodextrin (beta-CD) and hydropropyl-beta-cyclodextrin (HPbeta-CD) were formed by the solvation method, and were characterized by DSC, X-ray diffractometry and FT-IR spectroscopy. PC liposomes incorporating PR as plain drug or inclusion complex were prepared using the dehydration-rehydration method and drug entrapment as well as drug release were estimated for all liposome types prepared. The highest PR entrapment value (80% of the starting material) was achieved for PC/Chol liposomes when the HPbeta-CD-PR (2:1, mol/mol) complex was entrapped. The leakage of vesicle encapsulated 5,6-carboxyfluorescein (CF) was used as a measure of the vesicle membrane integrity. As judged from our experimental results liposomes which encapsulate beta-CD-PR complexes are significantly less stable (when their membrane integrity is considered) compared to liposomes of identical lipid compositions which incorporate plain drug or even (in some cases) non-drug incorporating liposomes, which were prepared and studied for comparison. Interestingly, liposomes which encapsulate HPbeta-CD-PR complexes, have very low initial CF latency values, indicating that the leakage of CF is a process of very high initial velocity. Interactions between lipid and cyclodextrin molecules may be possibly resulting in rapid reorganization of the lipid membrane with simultaneous fast release of CF molecules. The release of PR from liposomes was highest when the drug was entrapped in the form of a complex with beta-CD. Nevertheless, the very high entrapment ability of PR in the form of HPbeta-CD-PR complexes in comparison to plain drug is a indubitable advantage of this approach.     

N-三甲基壳聚糖包覆牛血清白蛋白脂质体的制备及质量影响因素研究

目的:制备N-三甲基壳聚糖(TMC)包覆的牛血清白蛋白(BSA)脂质体,并考察其质量影响因素。方法:采用逆相蒸发法制备BSA脂质体,壳聚糖与碘甲烷进行季胺化反应合成TMC,用于脂质体包衣,制备TMC包覆的BSA脂质体。采用高速离心考马斯亮蓝G-250法测定包封率,考察脂类大豆卵磷脂(PC):胆固醇(CH):磷脂酰丝氨酸(PS)组成比、TMC与脂相质量比、离子强度对脂质体包封率和粒径的影响。结果:所考察因素对粒径和包封率均有影响,以脂类组成PC:CH:PS(8:9:1)、TMC与脂相质量比0.25:1、离子强度小于20 mmol·L~(-1)为宜,所制脂质体包封率为(46.82±2.07)%。结论:TMC可包覆BSA制备脂质体,所得制剂粒径均匀,稳定性好。     

Effect of surfactants on the stability of modified egg-yolk phosphatidyl choline liposomes

Disintegration by surfactants on egg-yolk phosphatidyl choline (PC) vesicles, stabilized with polycholesteryl methacrylate and carboxy methyl chitosan, was investigated by measuring the amount of marker dye (bromothymol blue) released from the vesicles. In all the studies at pH 7.4 anionic and nonionic surfactants caused vesicle disintegration at low concentrations while cationic surfactants produced breakdown of vesicles at high concentrations. It was found that the modified liposomes disintegrated in the following order: Polymeric liposomes less than carboxymethyl chitosan coated/stearic acid/oleic acid containing PC liposomes less than cholesteryl methacrylate monomer containing PC liposomes/PC liposomes Polymeric liposomes were found to be the most stable compared with all other types. This may be explained due to the filling of the pores in the lipid structure which in turn block the surfactant penetration into phospholipid bilayers. In contrast to unsaturated fatty acid (oleic acid) saturated fatty acid (stearic acid) containing liposomes are more stable.     

Preparation and properties of poly(vinyl alcohol)-stabilized liposomes

The purpose of this work is to evaluate the improvement in physical stability of poly(vinyl alcohol) (PVA) modified liposomes. Liposomes composed of soya phosphatidylcholile (SPC) and cholesterol (1:1 molar ratio) were prepared by reverse phase evaporation method. Two types of interaction between liposome and PVA were investigated: PVA addition into lipid bilayer during liposome preparation and coating of already formed liposomes with PVA. The microparticles system was morphologically characterized by transmission electron microscopy (TEM) and particles analysis. Changes in particles size and zeta potential confirmed the existence of a thick polymer layer on the surface of liposomes. The amount of PVA adsorbing to liposomes and the encapsulation efficiency increased with increasing polymer concentration. The physical stability was evaluated by measuring the release rate of contents at 20 and 37 degrees C, the PVA modified liposomes were more stable than the conventional liposomes. Comparing with PVA-coated liposomes, the liposomes with PVA addition to the bilayer were more stable, and had higher entrapment efficiency.     

Effect of bovine serum albumin on the stability of methotrexate-encapsulated liposomes

The effect of bovine serum albumin (BSA) on the encapsulation efficiency and stability of liposomes containing methotrexate (MTX) having different surface charges and cholesterol contents were investigated. The encapsulation efficiency of MTX was lower and the release of MTX was faster by the addition of BSA. The leaking of MTX from lipid bilayer depends upon the BSA concentrations. These results may be derived from the interaction of BSA with lipid bilayers. The dynamic structural changes of BSA were monitored indirectly using circular dichroism spectra. Observed dynamic structural changes of BSA with liposomes are presumed to reflect the interaction of BSA with liposomes. Negatively charged liposomes have more strong interaction with BSA than neutral and positively charged liposomes. BSA attacks lipid bilayers whether it is at the inner or at the outer phase of lipid bilayer and induces leakage of entrapped MTX. Especially, negatively charged liposomes are more sensitive than others. The inclusion of cholesterol in the lipid layers inhibits the interaction of BSA with liposomes and shows protective effect against BSA-induced leakage of MTX. To endure the attacking of BSA, liposomes as drug carriers should be made using cholesterol.     

The effect of particle structure of chitosan-coated liposomes and type of chitosan on oral delivery of calcitonin

To optimize the properties of chitosan-coated liposomes for oral administration of peptide drugs, we examined the effect of type of chitosan and the structure of liposomal systems on the mucoadhesiveness of liposomes and resultant pharmacological effects of the liposomal peptide drug. A low-molecular weight chitosan (LCS) and a high-molecular weight chitosan (CS) were used as coating polymers of liposomes containing elcatonin (eCT). The muco-penetrative behaviors across the mucous gel layer covering the intestinal epithelial cells and the pharmacological effect after intragastric administration were determined in rats. The results showed that both LCS-coated liposomes (LCS-Lips) and CS-coated liposomes (CS-Lips) could permeate the mucous layer in the small intestine. The most interesting result was that LCS-Lips containing eCT showed remarkably more prolonged effectiveness in decreasing the blood calcium concentration than did CS-Lips containing eCT, moreover, it was also found that LCS had more efficiency to protect eCT from the enzymatic degradation than CS. In comparing the area above the plasma calcium concentration time curves (AAC) values among eCT-containing liposomes with different structures, i.e. eCT adsorbed on coated liposomes (eCT-ad-CS-Lip, eCT-ad-LCS-Lips) and eCT encapsulated in coated liposomes (eCT-encap-CS-Lips, eCT-encap-LCS-Lips), eCT-encap-CS-Lip showed much higher effectiveness than eCT-ad-CS-Lip. However, the AAC value for eCT-ad-LCS-Lip was comparable to that for eCT-encap-CS-Lip, while the value for eCT-ad-CS-Lip was nearly zero. These results suggested that LCS is a good mucoadhesive polymer candidate for enhancing the bioavailability of orally administered peptide containing liposomes, while encapsulation of eCT within the liposomal particles is important to protect eCT against enzymatic degradation in the gastrointestinal (GI) tract.     

Preparation, characterization, and biodistribution study of technetium-99m-labeled leuprolide acetate-loaded liposomes in ehrlich ascites tumor-bearing mice

The purpose of this study was to prepare conventional and sterically stabilized liposomes containing leuprolide acetate in an attempt to prolong the biological half life of the drug, to reduce the uptake by reticuloendothelial system (RES), and to reduce the injection frequency of intravenously administered peptide drugs. The conventional and sterically stabilized liposomes containing leuprolide acetate were prepared by reverse phase evaporation method and characterized for entrapment efficiency and particle size. Radiolabeling of leuprolide acetate and its liposomes was performed by direct labeling with reduced technetium-99m. Its biodistribution and imaging characteristics were studied in ehrlich ascites tumor (EAT)-bearing mice after labeling with technetium-99m. The systemic pharmacokinetic studies were performed in rabbits. A high uptake by tumor was observed by sterically stabilized liposome containing leuprolide acetate compared with free drug and conventional liposomes. The liver/tumor uptake ratio of free drug, conventional (LL), and sterically stabilized liposomes (SLL5000 and SLL2000) was found to be 20, 7.99, 1.63, and 1.23, respectively, which showed the increased accumulation of sterically stabilized liposomes in tumor compared with the free drug and conventional liposomes at 24 hours postinjection. Liver uptake of sterically stabilized liposomes was still 7-fold less than the conventional liposomes. The marked accumulation of liposomes in the tumor-bearing mice was also documented by gamma scintigraphic studies. The findings demonstrate the distribution of these liposomes within solid tumor and prove that the sterically stabilized liposomes experience increased tumor uptake and prolonged circulation half life. Hence these findings will be relevant for the optimal design of long circulating liposomes for the peptide drugs and for targeting of liposomes toward tumor.     

Properties of liposomes coated with hydrophobically modified chitosan in oral liposomal drug delivery

Chitosan (CS) has been widely used as an adhesive coating polymer for oral liposomal drug delivery systems because of its adhesive properties on mucous layers. The coating mechanism or interaction of chitosan and liposomes or mucin mainly depends on electrostatic forces. Thus, to enhance the adhesive properties of chitosan, a hydrophobically modified chitosan, i.e., dodecylated chitosan (DC), was synthesized. BIACORE results showed that both CS and DC could interact with mucin. Differences in sensorgram patterns between chitosan-mucin and dodecylated chitosan-mucin were observed and tentatively attributed to differences in binding kinetics. The zeta potential of dodecylated chitosan-coated liposomes (DC-Lip) showed positive values in both liposomal formulations, i.e., negatively charged and neutral-charge liposomes. These results indicated that DC could be considered a more suitable polymer for coating neutral-charge liposomes than CS because the hydrophobic side chain of DC inserts itself into the lipid bilayer of liposomes. Moreover, CS seemed to be less effective in the coating of a neutral-charge liposome because of the low positive values of its zeta potential. CS provided solely electrostatic forces when used for coating liposomes while DC provided electrostatic and hydrophobic forces due to the long alkyl chain in its backbone. Confocal Laser Scanning Microscopy (CLSM) images indicated that both chitosan-coated liposomes (CS-Lip) and DC-Lip could adhere to and penetrate through the small intestine of rats after oral administration. The pharmacological results showed that DC-Lip had a greater effect in decreasing blood calcium concentration during the first 12 h compared with CS-Lip. Therefore, it can be concluded that dodecylated chitosan can be useful in designing oral liposomal drug delivery systems.     

Effect of salts on the entrapment of calf thymus DNA into liposomes

To correlate the conformational changes of DNA (Calf Thymus) with entrapment of DNA into lipsomes, the effect of ions(Na⁺, Mg⁺⁺) on the entrapment of calf thymus DNA into liposomes was investigated. The effect of divalent ion(Mg⁺⁺) on the structural changes of DNA indicated by decrease of observed ellipticity at 274 nm and nonspecific binding of DNA to lipid bilayers was greater than monovalent ion(Na⁺). But the efficiency of DNA encapsulated was not altered. These results show that entrapment of DNA into liposomes is not due to nonspecific binding and structural changes because of electrostatic forces but to mechanical capture of DNA by the internal aqueous space of liposomes although divalent ion contributes large structural changes and more nonspecific association of DNA with liposomes due to strong charges.     

Encapsulation of lipopeptides within liposomes: effect of number of lipid chains, chain length and method of liposome preparation

The purpose of this study was to systematically investigate the effect of lipid chain length and number of lipid chains present on lipopeptides on their ability to be incorporated within liposomes. The peptide KAVYNFATM was synthesized and conjugated to lipoamino acids having acyl chain lengths of C8, C12 and C16. The C12 construct was also prepared in the monomeric, dimeric and trimeric form. Liposomes were prepared by two techniques: hydration of dried lipid films (Bangham method) and hydration of freeze-dried monophase systems. Encapsulation of lipopeptide within liposomes prepared by hydration of dried lipid films was incomplete in all cases ranging from an entrapment efficiency of 70% for monomeric lipoamino acids at a 5% (w/w) loading to less than 20% for di- and trimeric forms at loadings of 20% (w/w). The incomplete entrapment of lipopeptides within liposomes appeared to be a result of the different solubilities of the lipopeptide and the phospholipids in the solvent used for the preparation of the lipid film. In contrast, encapsulation of lipopeptide within liposomes prepared by hydration of freeze-dried monophase systems was high, even up to a loading of 20% (w/w) and was much less affected by the acyl chain length and number than when liposomes were prepared by hydration of dried lipid films. Freeze drying of monophase systems is better at maintaining a molecular dispersion of the lipopeptide within the solid phospholipid matrix compared to preparation of lipid film by evaporation, particularly if the solubility of the lipopeptide in solvents is markedly different from that of the polar lipids used for liposome preparation. Consequently, upon hydration, the lipopeptide is more efficiently intercalated within the phospholipid bilayers.     

Physicochemical properties of liposomes incorporating hydrochlorothiazide and chlorothiazide

In an attempt to study the effect of hydrophobic drugs on liposome properties, multilamellar liposomes (MLV) consisting of phosphatidylcholine (PC) and incorporating chlorothiazide (CT) or hydrochlorothiazide (HCT), were prepared and characterized. Liposome size, surface charge, stability (in buffer, plasma and sodium cholate) and calcium-induced aggregation were studied for drug-incorporating liposomes and empty liposomes for comparison. Results show that drug incorporation affects liposome size, z-potential and stability in presence of buffer and plasma proteins. Indeed, drug-incorporating liposomes are slightly larger and have a negative surface charge, which increases with the amount of drug incorporated in the lipid membrane. The membrane integrity of drug incorporating liposomes (in absence and presence of plasma proteins) is significantly higher when compared with that of empty liposomes (for both drugs studied). On the contrary, vesicle membrane integrity in presence of sodium cholate and calcium induced vesicle aggregation, are not affected by drug incorporation. Leakage of thiazides from liposomes was demonstrated to be induced by dilution. Low amounts of thiazides (around 10-15%) are released when lipid concentration is over 0.1 mM, while further dilution increased drug leakage exponentially. Concluding, results demonstrate that the presence of HCT or CT in liposome membranes has a significant effect on main vesicle properties, which are known to influence vesicle targeting ability. Thereby, it is very interesting to continue studies in this respect, especially with more lipophilic drugs.     

Liposomes with nifedipine and nifedipine-cyclodextrin complex: calorimetrical and plasma stability comparison

Inclusion complexes of nifedipine with 2-hydroxypropyl-ß-cyclodextrin (HPβCD) were formed by the spray- and freeze-drying methods. Nifedipine or its inclusion complexes (Nifedipine-CD complex I and II) were incorporated into liposomes prepared by the ethanol injection method. The highest entrapment value (77.7% of the starting material) was achieved for liposomes with N-CD complex II. The interaction of nifedipine with lipid bilayers was measured calorimetrically. DPPC liposomes mixed with nifedipine or N-CD complex II showed a slight shift of the transition temperature of DPPC towards lower temperatures compared to DPPC liposomes alone or mixed with HPßCD. However, with nifedipine, an additional transition peak was seen at lower temperatures in the second and all subsequent scans which could not be detected for the N-CD complex. Plasma stability studies showed that liposomes containing N-CD complex II are more stable than liposomes containing nifedipine. Encapsulation of drug-cyclodextrin complexes into liposomes can increase the entrapment of the lipophilic drug and reduce its release from the carrier.     

Mucoadhesive chitosan-coated liposomes: characteristics and stability

Lecithin liposomes, empty or containing FITC-dextran, were prepared by the ethanol injection method. Three different types of chitosans with different molecular weight and degrees of deacetylation were used (Seacure 113, 210 and 311). Chitosan coating was carried out by mixing the liposomal suspension with the chitosan solution followed by incubation. The size of liposomes was measured before and after polymer coating by an image analysis technique. The mean diameter of liposomes containing FITC-dextran was in the size range 250-280nm, whereas the size after coating was 300-330nm, regardless of chitosan type. All chitosan-coated liposomes were of spherical shape and no morphological differences between uncoated and coated liposomes were observed. Liposomes with FITC-dextran, originally entrapping 50% of the marker substance taken in the preparation and coated in the presence of unentrapped marker substance, contained 60-65%of the marker substance. The highest entrapment was found for liposomes coated with medium molecular weight chitosan. The stability of chitosan-coated liposomes in simulated gastric fluid was significantly higher as compared to uncoated liposomes. One can conclude that chitosan is stabilizing the original liposomal structure and protecting liposomally entrapped drug.     

Mucoadhesive chitosan-coated liposomes: characteristics and stability

Lecithin liposomes, empty or containing FITC-dextran, were prepared by the ethanol injection method. Three different types of chitosans with different molecular weight and degrees of deacetylation were used (Seacure 113, 210 and 311). Chitosan coating was carried out by mixing the liposomal suspension with the chitosan solution followed by incubation. The size of liposomes was measured before and after polymer coating by an image analysis technique. The mean diameter of liposomes containing FITC-dextran was in the size range 250-280 nm, whereas the size after coating was 300-330 nm, regardless of chitosan type. All chitosan-coated liposomes were of spherical shape and no morphological differences between uncoated and coated liposomes were observed. Liposomes with FITC-dextran, originally entrapping 50% of the marker substance taken in the preparation and coated in the presence of unentrapped marker substance, contained 60-65% of the marker substance. The highest entrapment was found for liposomes coated with medium molecular weight chitosan. The stability of chitosan-coated liposomes in simulated gastric fluid was significantly higher as compared to uncoated liposomes. One can conclude that chitosan is stabilizing the original liposomal structure and protecting liposomally entrapped drug.     

结肠定位壳聚糖包衣氟尿嘧啶脂质体的制备、形态与体外释放

目的探讨药物结肠定位壳聚糖包衣脂质体的制备、形态及其在体外释药特性。方法用罗丹明B异硫氰酸(RBITC)和Bodipy-PC分别标记壳聚糖和磷脂,用前体脂质体方法制备氟尿嘧啶脂质体,利用激光扫描共聚焦显微镜观察壳聚糖包衣脂质体的形态;考察壳聚糖包衣脂质体在人工胃液、人工肠液和人工结肠液中的释放。结果 脂质体包衣前后粒径分别为2.071和2.750 μm。壳聚糖能较好地包覆脂质体;3种脂质材料不同的包封率分别为99%,61%,72%。未包衣的脂质体在人工胃液中4 h已释放完全,而包衣脂质体在人工胃液4 h释放6.3%,在人工肠液中8 h仅释放6.8%,但在人工结肠液中释药明显加快,t1/2为3.63 h。结论结肠定位壳聚糖包衣脂质体制备可行,在人工结肠液中,体外释放符合Higuchi方程。     

A targeted liposome delivery system for combretastatin A4: formulation optimization through drug loading and in vitro release studies

Efficient liposomal therapeutics require high drug loading and low leakage. The objective of this study is to develop a targeted liposome delivery system for combretastatin A4 (CA4), a novel antivascular agent, with high loading and stable drug encapsulation. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, and distearoyl phosphoethanolamine-PEG-2000 conjugate (DSPE-PEG) were prepared by the lipid film hydration and extrusion process. Cyclic arginine-glycine-aspartic acid (RGD) peptides with affinity for alphav beta3-integrins overexpressed on tumor vascular endothelial cells were coupled to the distal end of polyethylene glycol (PEG) on the liposomes sterically stabilized with PEG (non-targeted liposomes; LCLs). Effect of lipid concentration, drug-to-lipid ratio, cholesterol, and DSPE-PEG content in the formulation on CA4 loading and its release from the liposomes was studied. Total liposomal CA4 levels obtained increased with increasing lipid concentration in the formulation. As the drug-to-lipid ratio increased from 10:100 to 20:100, total drug in the liposome formulation increased from 1.05+/-0.11 mg/mL to 1.55+/-0.13 mg/mL, respectively. When the drug-to-lipid ratio was further raised to 40:100, the total drug in liposome formulation did not increase, but the amount of free drug increased significantly, thereby decreasing the percent of entrapped drug. Increasing cholesterol content in the formulation decreased drug loading. In vitro drug leakage from the liposomes increased with increase in drug-to-lipid ratio or DSPE-PEG content in the formulation; whereas increasing cholesterol content of the formulation up to 30 mol-percent, decreased CA4 leakage from the liposomes. Ligand coupling to the liposome surface increased drug leakage as a function of ligand density. Optimized liposome formulation with 100 mM lipid concentration, 20:100 drug-to-lipid ratio, 30 mol-percent cholesterol, 4 mol-percent DSPE-PEG, and 1 mol-percent DSPE-PEG-maleimide content yielded 1.77+/-0.14 mg/mL liposomal CA4 with 85.70+/-1.71% of this being entrapped in the liposomes. These liposomes, with measured size of 123.84+/-41.23 nm, released no significant amount of the encapsulated drug over 48 h at 37 degrees C.     

Preparation and characterization of liposomes encapsulating chitosan nanoparticles

Liposomes are an important colloidal carrier system for controlled drug delivery. However some highly hydrophilic small molecules are difficult to entrap into liposomes and store stably, resulting in poor encapsulation efficiency and fast leakage. In the present work, fluorescein sodium (FS) was used as a model drug that was loaded into chitosan nanoparticles and then encapsulated into liposomes by reverse-phase evaporation (RPV). The encapsulation efficiency, particle size, zeta potential, release in vitro and pharmacokinetics in rats were determined in order to characterize the novel drug delivery system. The entrapment efficiency was above 80% in nanoparticles (Np) and 95% in liposomes encapsulating the nanoparticles (Lip-Np). The Lip-Np was composed of soybean phospholipids, cholesterol and chitosan, which the average diameter was 202.6 nm and zeta potential was -34.8 mV. The release rate of fluorescein sodium from Lip-Np was slower than from Np and liposomes. FS in Lip-Np administered to rats exhibited prolonged circulation and higher bioavailability than FS in Np. The results indicated that liposomal release kinetics can be controlled by encapsulating nanoparticles and thus solid-cored liposomes can be used as a potential drug delivery system.     

阿昔洛韦多囊脂质体的制备工艺优选

目的:制备包封率高、稳定性好的阿昔洛韦(ACV)多囊脂质体。方法:采用复乳法制备ACV多囊脂质体,以包封率为指标,以润滑剂三油酸甘油酯量(A)、药脂比(B)、缓冲液的pH值(C)及辅助乳化剂吐温-80的用量(D)为因素,设计正交试验优选工艺;采用紫外分光光度法测定其中主药含量并计算包封率;考察优选工艺所制制剂不同条件下7d内包封率的变化并计算渗漏率。结果:最佳工艺为A0.50g、B5∶150、C6.5、D0.40g,所制多囊脂质体包封率为85.82%,常温条件下贮存7d渗漏率为5.84%。结论:采用优选工艺制备的ACV多囊脂质体方法简单,包封率较高,常温下较稳定。