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OBJECTIVE:To prepare Bevacizumab(BEV)multivesicular liposomes(BEV-MVLs)with sustained-effect,and to study their in vitro release characteristics. METHODS:BEV-MVLs were prepared by double emulsion method. Box-Behnken design-response surface methodology was used to optimize the prescription with the concentration of glycerol trioleate(TO)in organic phase,ratio of 1,2-dioleoyl-sn-glycero-3-phosphocholine(DOPC)-cholesterol(CH)(mol/mol),the concentration of L-lysine in external water phase as factors,using encapsulation rate as index. The morphology of BEV-MVLs was observed by inverted fluorescence microscope and SEM;particle size was determined by laser particle size analyzer;the BEV content was determined by HPLC and calculate the encapsulation rate and in vitro accumulative release rate.RESULTS:The optimized prescription was as follows as TO of 2.72 mmol/L in organic phase,DOPC-CH ratio of 0.67(mol/mol)and L-lysine of 40 mmol/L in external water phase. The encapsulation rate of BEV-MVLs was(80.65±4.42)%(n=3),and relative error of it to predicted value was 2.54%. The liposomes were spherical in appearance shape and uniform in size,and they were typical non-concentric vesicle structure with average particle size of 16.80 μm. 30 d in vitro accumulative release rate was about 92%. CONCLUSIONS:Prepared BEV-MVLs show sustained-effect,and their encapsulation rate reaches the expected effect.
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Objective To investigate the characteristics of hyaluronic acid-uricase multivesicular liposomes (UHMVLs) in vitro and the pharmacodynamics of UHMVLs in rats. Methods UHMVLs was prepared by multiple emulsion method. The entrapment efficiency and physicochemical properties were detected. Twelve healthy male SD rats were enrolled in this study. The rat model of hyperuricemia was established with hypoxanthine and oteracil potassium, while the normal rats (n=3) were set as controls. Intravenous UHMVLs, uricase (UC) and nothing were given to the rats of UHMVLs group (n=3), UC group (n=3) and hyperuricemia model group (n=3), respectively; the levels of serum uric acid (UA) were detected in rats of the 4 groups. Results The average entrapment efficiency of UHMVLs was (62.48±3.87)%. The optimum temperatures of UHMVLs and UC were 40°, while the optimum pH values of UHMVLs and free UC were 8.0 and 8.5, respectively. The activity of UC in UHMVLs was significantly higher than that in free UC at the same temperature (20-70°) and pH value (6.5-9.5) (P<0.05). UHMVLs was more effective than free UC in decreasing serum UA in rats with hyperuricemia at all time points (P<0.05), except for 1 h, 36 h and 48 h. Conclusion Under the same condition, UHMVLs can improve not only the activity, but also the stability of UC. UHMVLs is more effective in decreasing serum uric acid in rats compared with free UC, which may pave a way for clinical application of UC.
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Objective:To establish a determination method for the content and entrapment efficiency of ropivacaine hydrochloride-loaded multivesicular liposomes. Methods: The separation of the multivesicular liposomes from the free drug was achieved by low-speed centrifugation. The concentration of ropivacaine hydrochloride in the supernatant and the multivesicular liposomes was determined by HPLC, and the entrapment efficiency was calculated. Results: The linear range of ropivacaine hydrochloride was 1. 0-80. 0μg· ml-1(r=0. 999 8). The average recovery was 99. 95% and RSD was 0. 72%(n=9). The content and entrapment efficiency of three batches of ropivacaine hydrochloride-loaded multivesicular liposomes was within the range of 99. 1%-100. 3% and 80. 06%-82. 14%, respectively. Conclusion:The method is simple and accurate, and can be used in the determination of content and entrapment efficien-cy of ropivacaine hydrochloride-loaded multivesicular liposomes.
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Objective To study the pharmacokinetics of neostigmine bromide multivesicular liposomes (NB-MVLs) and conventional neostigmine bromide (NB) injection in rats. Methods Twelve healthy rats, half male and half female, were randomly divided into two groups. One group was injected with NB-MVLs and the other with reference NB (0.15 mg/kg). RP-HPLC was used to examine neostigmine concentrations in rat plasma at different time points, and the pharmacokinetic parameters and relative bio-availability were calculated. Results Pharmacokinetic parameters of NB-MVLs and NB were as follows: AUC0-t (35.56±4.62) mg·h·L-1 vs (15.97±5.22) mg·h·L-1;Tmax(2.40±0.89) h vs (0.45±0.11) h; Cmax (2.49±0.31) mg/L vs (4.61±0.91) mg/L; and t1/2 (15.14± 6.81) h vs (1.79±0.27) h, respectively. AUC0-t, AUC0-∞ and Cmax were studied by DAS 2.1.1 software for double unilateral t test and [1-2α] 90% confidence interval, and Tmax was precessed by Wilcoxon nonparametric test to evaluate the bioequivalence of NB-MVLs and NB. The result showed that NB-MVLs and NB were not bioequivalent. Conclusion Neostigmine in the form of multivesicular liposomes has improved bioavailability and stable drug release; NB-MVLs and NB are not bioequivalent.
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Aim: To prepare ropivacaine hydrochloride multivesicular liposomes, and to study the physicochemical properties and drug release behavior in vitro. Methods: Ropivacaine hydrochloride multivesicular liposomes were prepared by the multiple emulsion method. Single factor experiments were utilized to study the factors which affect the encapsulation efficiency of multivesicular liposomes. The formulation and pharmaceutical process were optimized by Box-Behnken experimental design, with the factors of encapsulation efficiency as the criteria. Three batches of the optimized multivesicular liposomes were prepared, and the encapsulation efficiency and in vitro release behavior were studied. Results: The particle size of the optimized multivesicular liposomes was uniform and 85% of them were well distributed in the range of 7-30 μm. The encapsulation efficiency was up to 90% when the ratios of lipid to drug, phospholipids to cholesterol and the amount of triolein was 1. 328:1(w/w) ,1.5: 1(w/ w) and 6 mmol/L, respectively. The release profile in vitro fitted to a first-order kinetics with the period of release up to 48 h in PBS buffer under 37 ℃. Conclusion: Ropivacaine hydrochloride multivesicular liposomes showed high encapsulation efficiency and significant sustained-release feature.
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OBJECTIVE:To prepare aciclovir multivesicular liposomes of high encapsulation efficiency and good stability. METHODS: Aciclovir multivesicular liposomes were prepared by multiple emulsion method. The preparation technology was optimized by orthogonal experiment with entrapment efficiency as index and the amount of lubricant glyceryl trioleate (A),drug/lipid ratio (B),pH of buffer solution (C) and the amount of tween-80 (D) as factors. The concentration of the aciclovir was determined by the UV spectrophotometry and the entrapment efficiency of the aciclovir multivesicular liposomes was computed. The change of the entrapment efficiency of the optimized preparations within 7 days in different conditions was investigated and the leaking rate was computed. RESULTS: The optimal technology was as follows: A 0.50 g,B 5∶150,C 6.5 and D 0.40 g. The entrapment efficiency of the aciclovir multivesicular liposomes was 85.82% and the leaking rate was 5.84% within 7 days under common temperature. CONCLUSIONS: The preparation technology of the aciclovir multivesicular liposomes is simple and the preparation is of high entrapment efficiency and good stability under common temperature.
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OBJECTIVE:To prepare multivesicular liposomes-sodium polymannuronate microspheres(MVLs-Alg)for protein drugs and to study the physico-chemical property and elementary stability of MVLs-Alg.METHODS:MVLs and Alg were used as matrix and BSA as a model protein drug,MVLs-Alg microspheres were prepared by interior/gelatin method.The relationship between MVLs and Alg was analyzed by differential thermal analysis and the effect of temperature(4,25,40 ℃)on entrapment efficiency and peroxide value of phospholipid in base material was investigated.RESULTS:The MVLs-Alg microspheres were spherical.Analyzed by DTA,it was considered that physical adsorption between MVLs and Alg was potentially existed.Storing for 90 days at 4,25,and 40 ℃ respectively,the encapsulation efficiency of the MVLs-Alg microsphereswere were 85.36%,63.75%,and 50.49%,respectively.The peroxide value of phospholipid increased increasingly,but not significant as compared with MVLs.CONCLUSIONS:The stability of MVLs-Alg microspheres was heightened compared with that of MVLs and which can be used for the delivery of protein drugs.
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OBJECTIVE:To optimize the preparation technology of substance P multivesicular liposomes(Depo-SP)and investigate its property.METHODS:Depo-SP was prepared by multiple emulsion method,with encapsulation efficiency taken as index,molar ratio of phospholipid to cholesterol(A),ultrasound emulsification time(B),volume ratio of colostrum to two-phase water(C)and coemulsifier concentration(D)as factors to design the orthogonal experiment for optimizing the preparation technology.The encapsulation efficiency,distribution of particle size,in vitro drug release profiles,phase transition temperature and melting point of the optimized preparation were determined.RESULTS:The optimized preparation conditions of Depo-SP were as follows:A-2:1,B=30 s,C=1:2 and D=2%.The encapsulation efficiency of the preparation reached 85%;the particle size stood at 0.75～27.75?m;the SP release in normal sodium was t_(1/2)=11 h and the sustained release maintained for 72 hours;the phase transition temperature was 34℃and the melting point was 110℃. CONCLUSION:The prepared Depo-SP had high encapsulation efficiency and stable in physical property,and it is an ideal sustained release preparation.
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Objective To prepare the sinomenine hydrochloride multivesicular liposomes with high entrapment efficiency and sustained release character.Methods Multiple emulsion method was used to prepare the sinomenine hydrochloride multivesicular liposomes.Uniform design was applied to optimize the formulation and pharmaceutical process.The shape,the particle size,and the release charcter of the liposome were evaluated.Results The sinomenine hydrochloride multivesicular liposomes prepared were spherical and the size of majority particles was in the range of 20—30 ?m and well distributed.The encapsulation efficiency was more than 80% and its in-vitro release profile accorded well with the Higuchi model with t1/2 up to 52.7 h.Conclusion The formulation and pharmaceutical process of the sinomenine hydrochloride multivesicular liposomes are stable and feasible with the high encapsulation efficiency and good sustained-release character.
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AIM:To establish a method of determining the entrapment efficiency of bulleyaconitine A multivesicular liposomes.METHODS:Bulleyaconitine multivesicular liposomes and its free bulleyaconitine were separated by centrifugalization.To calculate the entrapment efficiency,total and free bulleyaconitine were assayed by HPLC.RESULTS:At low speed,the rate of rotation did not affect the determination of entrapment efficiency.The average entrapment efficiency of three lot samples was 87.12%.CONCLUSION:Entrapment efficiency of bulleyaconitine multivesicular liposomes could be evaluated simply and quickly by centrifugalization.