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Recently, metformin (Met) has shown to have antineoplastic properties in cancer treatment by improving hypoxic tumor conditions, and causing reduction in the synthesis of biomolecules, which are vital for cancer growth. However, as an orally administered drug, Met has low bioavailability and rapid renal clearance. Thus, the goal of this study was to vectorize Met inside liposomes in the context of triple negative breast cancer (TNBC), which currently lacks treatment options when compared to other types of breast cancer. Vectorization of Met inside liposomes was done using Bangham method by implementing double design of experiment methodology to increase Met drug loading (minimum-run resolution V characterization design and Box-Behnken design), as it is generally extremely low for hydrophilic molecules. Optimization of Met-loaded liposome synthesis was successfully achieved with drug loading of 190 mg/g (19% w/w). The optimal Met-liposomes were 170 nm in diameter with low PdI (< 0.1) and negative surface charge (-20 mV), exhibiting sustained Met release at pH 7.4. The liposomal Met delivery system was stable over several months, and successfully reduced TNBC cell proliferation due to the encapsulated drug. This study is one the first reports addressing liposome formulation through thin-film hydration using two design of experiment methods aiming to increase drug loading of Met. [ABSTRACT FROM AUTHOR]

In the present study, nanoliposomes with tuneable structure elasticity were prepared by reverse-phase evaporation. Both Fluorescence Polarization and Fluorescence Resonance Energy Transfer was employed to characterize the structural elasticity of resultant nanoliposomes. Temozolomide, a kind of hydrophilic drug as the first-line treatment choice for glioblastoma, was encapsulated into nanoliposomes. The results showed that the flexibility of nanoliposomes gradually increased with sodium cholate, while decreasing with cholesterol, Labrafac CC and Labrafac PG adding. Furthermore, the structural flexibility of nanoliposomes was positively correlated with the encapsulation efficiency and release rate and cellular uptake. Our research reveals the structural flexibility of nanoliposomes could affect in vitro characteristics and thereafter in vivo behaviors of nanoliposomes. [ABSTRACT FROM AUTHOR]

The purpose of this study was to optimize the preparation conditions of podophyllotoxin liposomes (PPT-Lips), and to investigate their effects on PC3 cells. PPT-Lips were prepared by using a thin-film dispersion method. In order to achieve maximum drug encapsulation efficiency (EE), the process and formulation variables were optimized by response surface methodology (RSM). The optimum preparation conditions were cholesterol to lecithin ratio of 3.6:40 (w/w), lipid to drug ratio of 15.8:1 (w/w), and the ultrasonic intensity of 35% (total power of 400 W). The experimental EE of PPT-Lips was 90.425%, which was consistent with the theoretically predicted value. The characterization studies showed that PPT-Lips were well-dispersible spherical particles with an average size of 106 nm and a zeta potential of –10.1 mV. A gradual and time-dependent pattern of PPT from liposomes was found in in vitro drug release with a cumulative release amount up to 70.3% in 24 h. Results of cell viability experiments on PC3 cells demonstrated that PPT-Lips exhibited more effective anticancer activity in comparison with free PPT. Therefore, PPT-Lips represent an efficient and promising drug delivery system for PPT. [ABSTRACT FROM AUTHOR]

Context: Pirfenidone (PFD) is an anti-fibrotic and anti-inflammatory agent indicated for the treatment of idiopathic pulmonary fibrosis (IPF). The current oral administration of PFD has several limitations including first pass metabolism and gastrointestinal irritation. Objective: The aim of this study is to investigate the feasibility of transdermal delivery of PFD using liposomal carrier system. Materials and methods: PFD-loaded liposomes were prepared using soy phosphatidylcholine (SPC) and sodium cholate (SC). Encapsulation efficiency (EE) of PFD in liposomes was optimized using different preparation techniques including thin film hydration (TFH) method, direct injection method (DIM) and drug encapsulation using freeze–thaw cycles.In vitrodrug release study was performed using dialysis membrane method. The skin permeation studies were performed using excised porcine ear skin model in a Franz diffusion cell apparatus. Results and discussion: The average particle size and zeta-potential of liposomes were 191 ± 4.1 nm and −40.4 ± 4.5 mV, respectively. The liposomes prepared by TFH followed by 10 freeze–thaw cycles showed the greatest EE of 22.7 ± 0.63%. The optimized liposome formulation was incorporated in hydroxypropyl methyl cellulose (HPMC) hydrogel containing different permeation enhancers including oleic acid (OA), isopropyl myristate (IPM) and propylene glycol (PG). PFD-loaded liposomes incorporated in hydrogel containing OA and IPM showed the greatest flux of 10.9 ± 1.04 μg/cm2/h across skin, which was 5-fold greater compared with free PFD. The cumulative amount of PFD permeated was 344 ± 28.8 μg/cm2with a lag time of 2.3 ± 1.3 h. Conclusion: The hydrogel formulation containing PFD-loaded liposomes can be developed as a potential transdermal delivery system. [ABSTRACT FROM PUBLISHER]

Context: Ropivacaine (RVC) is an aminoamide local anesthetic widely used in surgical procedures. Studies with RVC encapsulated in liposomes and complexed in cyclodextrins have shown good results, but in order to use RVC for lengthy procedures and during the postoperative period, a still more prolonged anesthetic effect is required. Objective: This study therefore aimed to provide extended RVC release and increased upload using modified liposomes. Materials and methods: Three types of vesicles were studied: (i) large multilamellar vesicle (LMV), (ii) large multivesicular vesicle (LMVV) and (iii) large unilamellar vesicle (LUV), prepared with egg phosphatidylcholine/cholesterol/α-tocopherol (4:3:0.07 mol%) at pH 7.4. Ionic gradient liposomes (inside: pH 5.5, pH 5.5 + (NH4)2SO4and pH 7.4 + (NH4)2SO4) were prepared and showed improved RVC loading, compared to conventional liposomes (inside: pH 7.4). Results and discussion: An high-performance liquid chromatography analytical method was validated for RVC quantification. The liposomes were characterized in terms of their size, zeta potential, polydispersion, morphology, RVC encapsulation efficiency (EE(%)) andin vitroRVC release. LMVV liposomes provided better performance than LMV or LUV. The best formulations were prepared using pH 5.5 (LMVV 5.5in) or pH 7.4 with 250 mM (NH4)2SO4in the inner aqueous core (LMVV 7.4in + ammonium sulfate), enabling encapsulation of as much as 2% RVC, with high uptake (EE(%) ∼70%) and sustained release (∼25 h). Conclusion: The encapsulation of RVC in ionic gradient liposomes significantly extended the duration of release of the anesthetic, showing that this strategy could be a viable means of promoting longer-term anesthesia during surgical procedures and during the postoperative period. [ABSTRACT FROM PUBLISHER]

The aim of this study is to prepare tea tree oil liposome (TTOL) and optimize the preparation condition by single factor experiment and statistical design. TTOL was prepared using a thin-film hydration with the combination of sonication method and the preparation conditions of TTOL were optimized with response surface methodology (RSM). The optimal preparation conditions for TTOL by response surface methodology were as follows: the mass ratio of PC and Cho 5.51, TTO concentration 1.21% (v/v) and Tween 80 concentration 0.79% (v/v). The response surface analysis showed that the significant (p < 0.05) second-order polynomial regression equations successfully fitted for all dependent variables with no significant (p > 0.05) lack of fit for the reduced models. Furthermore, the interaction of the mass ratio of PC/Cho and TTO concentration had a significant effect. The amounts of Tween 80 required were also reduced with RSM. Under these conditions, the experimental encapsulation efficiency of TTOL was 97.81 ± 0.33%, which was close with the predicted value. Therefore, the optimized preparation condition was very reliable. The increased entrapment efficiency would significantly improve the TTO stability and bioavailability. [ABSTRACT FROM AUTHOR]

Vesicular phospholipid gels (VPGs) represent semi-solid phospholipid dispersions. Their morphology is truly vesicular with aqueous compartments both within the core of the vesicles and in-between the vesicles. VPGs are suited to carry both hydrophilic, amphiphilic and lipophilic drugs. Their drug load is stable since there is no concentration gradient between the vesicles' core and the surrounding water phase. VPGs are suited to release drugs in a controlled manner, and thus may serve as depot implants. When blended with excess aqueous medium VPGs are easily converted into small-sized liposome (SUV) dispersions showing high encapsulation efficiencies for all kinds of drugs. VPG-formulations with various cytostatic drugs have been tested successfully in human xenografts. Obviously, the vesicles protect the drugs from premature metabolic inactivation and/or elimination and guide them to solid tumors with enhanced vascular permeability (passive targeting). Furthermore, when mounted on a filter support, VPGs represent a tight diffusion barrier suitable for screening of oral drug permeability, as demonstrated by a set of 21 drug compounds. Permeability values were shown to fit well with human absorption in vivo, indicating that the model is suited for rapid screening of passive transport properties of new chemical entities. [ABSTRACT FROM AUTHOR]

Liposomal delivery systems for water-soluble bioactives were prepared using the pro-liposome and the microfluidization technologies. Iron, an essential micronutrient as ferrous sulfate and ascorbic acid, as an antioxidant for iron were encapsulated in the liposomes. Liposomes prepared by the microfluidization technology using 6% (w/w) concentration of the lipid encapsulated with ferrous sulfate and ascorbic acid had particle size distributions around 150 to 200 nm, whereas liposomes from the pro-liposome technology resulted in particle sizes of about 5 μm. The encapsulation efficiency of ferrous sulfate was 58% for the liposomes prepared by the microfluidization using 6% (w/w) lipid and 7.5% of ferrous sulfate concentrations, and it was 11% for the liposomes from pro-liposome technology using 1.5% (w/v) lipid and 15% of ferrous-sulfate concentration. Both the liposomes exhibited similar levels of oxidative stability, demonstrating the feasibility of microfluidization-based liposomal delivery systems for large-scale food/nutraceutical applications. [ABSTRACT FROM AUTHOR]

Liposomes loaded with ketorolac tromethamine salt were prepared by using a thin layer evaporation method. The physical properties of liposomes were studied by using atomic force microscopy (AFM) and transmission electron microscopy (TEM). The relationship between lipid composition, encapsulation efficiency, vesicle size, and the release of ketorolac tromethamine-loaded liposomes was studied. The drug content was found to be dependent on the lipidic composition used in the preparations and, in particular, vesicles containing both cationic lipids (dimethyldioctadecylammonium bromide and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride), and phosphatidylcholine had a higher entrapped efficiency than liposomes with phosphatidylcholine alone or in the presence of cholesterol. Finally, the cationic liposomes appear to be useful as carriers for ketorolac tromethamine to control its in vitro release. [ABSTRACT FROM AUTHOR]

Methods for encapsulation of a drug into liposomes should preferably result in a high encapsulation efficiency and a high encapsulation capacity. Our studies were focussed on the establishment of an efficient encapsulation procedure of the radical scavenging protein, rh-Cu/Zn-SOD, into liposomes with the cross flow injection method. Limitations to increase the encapsulation efficiency are caused by the enclosed aqueous volume, by the lipid concentration, the aspired vesicle size and the final ethanol concentration. Our research was performed to maximize the encapsulation following several strategies of injecting higher lipid concentrations into the aqueous phase. The one way triple technique, a sophisticated preparation procedure is presented, which enables three times higher encapsulation rates in comparison to standard procedures. Additionally, scalability studies demonstrate reproducibility independent of the preparation volume. Vesicle size distribution and encapsulation efficiency remain constant. Furthermore, special attention is paid on reproducibility of prepared liposomes, scale-up and on long term stability of the lipid vesicles. [ABSTRACT FROM AUTHOR]