Vitamin C as a shelf-life extender in liposomes

Abstract The objective of this study was to evaluate the influence of vitamin C (VC) on the stability of stored liposomes under different climatic conditions. Liposomal formulations containing 1 mg/mL of VC (LIP-VC) and blank formulations (LIP-B) were prepared by the reverse-phase evaporation method. After preparation, they were characterized according to their refractive index, average vesicle diameter, polydispersity index (PDI), zeta potential, pH, content, encapsulation efficiency (EE%), morphology, stability and antioxidant activity. For stability, LIP-VC and LIP-B were stored in different climatic conditions (4 °C, 25 °C and 40 °C) for 30 days. The LIP-VC presented 1.3365 refractive index, 161 nm of mean diameter, 0.231 PDI, -7.3 mV zeta potential, 3.2 pH, 19.4% EE%, spherical morphology, 1 mg/mL of VC content, and antioxidant activity of 12 and 11.4 μmol of TE/mL for the radical DPPH and ABTS+, respectively. During stability, the LIP-B stored in 40 °C showed an instability in the parameters: PDI, vesicle size and zeta potential after 15 days, while the LIP-VC remained stable in its size and PDI for 30 days. After that, it is shown that VC can be used as an antioxidant and stabilizer in liposomes to increase the stability and shelf-life of vesicles.

Preparation Process of Baicalin Liposomes by Reverse Phase Evaporation / 中国药学杂志

OBJECTIVE: To study the preparation technology of baicalin glycosides liposomes. METHODS: Baicalin liposomes modified by vitamin E and Tween 80 were prepared by reverse phase evaporation method. The free drug was separated by ultracentrifugation and the encapsulation rate was determined by UV spectrophotometry. Based on the results from single factor tests, orthogonal experimental design was used to investigate the factors influencing the envelopment rate of liposomes. The baicalin liposomes prepared by the optimized process were characterized for particle size, Zeta potential, and morphology. RESULTS: The optimum conditions for the preparation of liposomes were as follows: the ratio of water phase to organic phase 1∶3, the concentration of baicalin 3 mg•mL-1, the ratio of cholesterol to soy lecithin 1∶6, dosage of vitamin E 2 mg,dosage of Tween 80 120 μL. The mean diameter was 52.2 nm, Zeta potential was -51.9 mV, the encapsulation rate was 70.22% and drug loading capacity was 3.18%. Transmission Electr Microscope(TEM) results showed that the shape of the liposomes was good, the particle size was relatively uniform and consistent with the results of laser granulometry. CONCLUSION: The stability of baicalin liposomes can be improved by the addition of vitamin E and Tween 80.

Formulation design and characterization of a non-ionic surfactant based vesicular system for the sustained delivery of a new chondroprotective agent

Diacerein is used for symptomatic relief and cartilage regeneration in osteoarthritis. Due to gastrointestinal side effects, poor aqueous solubility and low bioavailability, its clinical usage has been restricted. The objective of the present study was to enhance its dissolution profile and to attain sustained release by designing a novel delivery system based on niosomes. Five niosomal formulations (F1-F5) with non-ionic surfactant (sorbitan monostearate) and cholesterol in varying ratios of 5:5, 6:4, 7:3, 8:2 and 9:1 were developed by the reverse-phase evaporation technique. The size and polydispersivity index (PDI) were found in the range of 0.608 µm to 1.010 µm and 0.409 to 0.781, respectively. Scanning electron microscopy (SEM) of the selected formulation (F3) revealed spherical vesicles, and 79.8% entrapment was achieved with F3 (7:3). Dissolution studies using the dialysis method showed sustained release behaviour for all formulations. The optimized surfactant-to-cholesterol concentration (7:3) in formulation F3sustained the drug-release time (T50%) up to 10 hours. Kinetic modelling exhibited a zero-order release (R2=0.9834) and the release exponent 'n' of the Korsmayer-Peppas model (n=0.90) confirmed non-fickian and anomalous release. The results of this study suggest that diacerein can be successfully entrapped into niosomes using sorbitan monostearate and that these niosomes have the potential to deliver diacerein efficiently at the absorption site.

A diacereína é usada para o alívio sintomático e para a regeneração da cartilagem na osteoartrite. Devido aos efeitos adversos gastrointestinais, baixa solubilidade aquosa e biodisponibilidade, o seu uso clínico tem sido restrito. O objetivo do presente estudo foi melhorar o perfil de dissolução deste fármaco e obter liberação prolongada através do planejamento de um novo sistema de liberação designado de niossoma. Cinco formulações distintas de niossomas (F1 a F5) contendo tensoativos não iônicos (monoestearato de sorbitano) e colesterol, em diferentes proporções, de 5:5, 6:4, 7:3, 8:2 e 9:1, foram desenvolvidas através da técnica de evaporacão de fase reversa. Os tamanhos e índices de polidispersibilidade (PDI) obtidos variam entre 0,608 e 1,01 µm e entre 0,409 e 0,7781, respectivamente. Imagens de microscopia electrônica de varrimento (SEM) da formulação selecionada (F3) revelaram vesículas esféricas. Obteve-se encapsulação de 79,8% com a formulação F3 (7:3). Estudos de dissolução usando o método de diálise demonstraram padrão de liberacão prolongada para todas as formulações. A proporção de tensoativo e colesterol (7:3) na formulacão F3 prolongou o tempo de liberação do fármaco (T50%) até 10 horas. Estudos de modelação cinética demonstraram ordem de liberacão zero (R2=0,9834) e o expoente de liberação "n" do modelo de Korsmayer-Peppas (n=0.90) confirmou a liberação não-fickiana e anômala. Os resultados deste estudo sugerem que a diacereína pode ser encapsulada com sucesso no interior de niossomas, utilizando monostearato de sorbitano, o qual tem potencial para liberar, eficientemente, a diacereína no local de absorção.

Preparation technology of sinomenine hydrochloride liposomes / 中草药

Objective: To prepare sinomenine hydrochloride (SIN-HCl) liposomes with high entrapment efficiency (EE) and to illustrate the effects of drug quantity and particle size on EE. Methods: Centrifugation sedimentation-centrifugation ultrafiltration was employed to determine EE of liposomes. Thin film hydration (TFH), reverse phase evaporation (REV), and ether injection (EI) were screened based on EE and formability of liposomes. The effects of water type, pH value, ion concentration of hydration liquid, pH gradient active drug loading, lecithin-cholesterol ratio, and drug-lipid ratio on EE of liposomes were investigated. The relationship between EE and the factors affecting the drug quantity and particle size was probed with a comprehensive design experiment. The stability of typical liposomes was evaluated at 4 °C. Results: The optimal preparation technology was TFH for SIN-HCl liposomes and citrate buffer solution (CBS) was the best hydration liquid. The liposome EE increased with the increase of pH values of CBS. When the pH value of CBS was fixed, the EE increased as a result of decrease in the ion concentration of CBS. pH gradient active drug loading led to increase of EE. The preferable hydration liquid for liposomes was CBS with pH value of 2.5. The optimal ratio of soybean lecithin to cholesterol was 6:1. Increasing ratios of SIN-HCl to soybean lecithin from 1:6 to 6:6 led to a slight decrease in EE of liposomes without probe signification. A quantitative relationship was established between the EE and drug quantity and liposome size. The EE of SIN-HCl liposomes prepared by certain particle size and drug quantity could reach over 80%. The typical liposomes showed a good stability. Conclusion: The technology of pH gradient active drug loading is able to prepare SIN-HCl liposomes with high EE.

Preparation of curcumin liposome and preliminary study on its stability / 重庆医科大学学报

Objective:To prepare curcumin liposome and investigate its stability.Methods:Curcumin liposome was prepared by the reversed-phase evaporation method and purified by exclusion chromatography with Sephadex-50.The optimum formation was selected by means of orthogonal design of experiment;Centrifugal acceleration experiment and determination of leakling ration were served to proved the liposome stability.Results:The optimum formula was as follows:the ratio of lecithin to drug was 60∶1;lecithin:cholesterol was 4∶1;pH of PBS was 6.5,ultrasonic time was 5min.The average entrapment efficiency for curcumin was 95.06%.Conclusion:The selected formulation and preparation technique of curcumin liposome is reasonable in prescription,practicable in techniques,high in encapsulation efficiency and good in stability.