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Objective: To prepare glycyrrhizic acid (GL)-Pluronic F127 (F127)/polyethylene glycol 1000 vitamin E succinate (TPGS) mixed nanomicelles (MMs) and improve oral absorption of GL. Methods: GL-F127/TPGS-MMs was prepared by thin film dispersion method. The encapsulation efficiency and drug loading of MMs were used as evaluation indexes. The formulation and process, including the ratio of F127 to TPGS, the concentration of polymer and GL, hydration temperature and time, were optimized by the single factor experiment. The morphology of MMs was investigated by transmission electron microscopy. The single-pass perfusion model was established in rats to investigate the intestinal absorption characteristics of GL-F127/TPGS-MMs with absorption rate constant (Ka) and apparent absorption coefficient (Papp) as evaluation indexes. Results: The optimal formulation and process of GL-F127/TPGS-MMs were as follows: TPGS 180 mg, F127 270 mg, GL 70 mg, hydration temperature 50 ℃ and hydration time 3 h. The prepared GL-F127/TPGS-MMs had good clarity and the particle size, polydispersity index, and Zeta potential were (28.20 ± 5.63) nm, 0.20 ± 0.06, and (-5.24 ± 1.55) mV, respectively. The encapsulation efficiency and drug loading were (97.57 ± 5.29) % and (13.13 ± 0.71) %, respectively. The MMs were spherical with distinct vesicle structure. The absorption of GL in the jejunum segment was significantly higher than that in the ileum segment (P < 0.05). Compared with raw GL, GL-F127/TPGS-MMs had a statistically significant higher absorption rate in the intestinal segment (P < 0.05). Conclusion: The prepared GL-F127/TPGS-MMs could significantly improve the absorption of GL in vivo.
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Objective: To develop the photosensitizer rose-bengal (RB)/upconverting nanoparticles (UCNPs)/dihydroartemisinin (DHA) co-encapsulated liposomes (LIP-RUD) and preliminarily study the in vitro inhibition effects on human colon cancer. Methods: The hydrophilic UCNPs were synthesized by solvothermal and ligand conversion and RB/UCNPs/DHA were encapsulated by thin-film dispersion method to obtain LIP-RUD. HPLC was performed to determine the loading ratio (LR) of RB and DHA. Zetasizer was used to evaluate the physiochemical properties of liposomes. The production of ROS was investigated by SOSG probe. In vitro cellular uptake of LIP-RUD was observed by confocal laser scanning microscopy (CLSM) and the cytotoxicity on HCT-116 cells was estimated by MTT assay. Results: LIP-RUD showed an average particle diameter of 150 nm with zeta potential of -12 mV. The LR of RB and DHA were 54.5% and 86.5%, respectively. The energy conversion efficiency of UCNPs and RB reached 49.8%. After irradiation, the singlet oxygen (1O2) was generated and 74.9% of encapsulated DHA was released from LIP-RUD at 12 h, which showed an improvement of up to 25.6% compared to the absence of laser irradiation group. In cellular experiments, LIP-RUD exerted improved cytotoxicity on HCT-116 cells. IC50 was 15.33 μmol/L under laser irradiation. Conclusion: LIP-RUD provides a new thought in the treatment of human colon cancer by the combination of photodynamic therapy (PDT) and chemotherapy, which is expected to enhance the penetration depth of PDT and the therapeutic effect of combination therapy.
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Objective: To prepare pH-sensitive drug releasing As2O3 loaded liposome (CaAs-LP) and evaluate it in vitro. Methods: CaAs-LP was prepared by thin film dispersion and ion precipitation method. The particle size, PDI, and Zeta potential of CaAs-LP were measured by Malvern particle size analyzer; The morphology of the liposome was investigated by transmission electron microscopy; The drug loading and entrapment efficiency of CaAs-LP by inductively coupled plasma emission spectrum. In vitro release characteristics of CaAs-LP under different pH conditions were investigated by dialysis bag method. MTT assay was used to investigate the toxicity of carrier and CaAs-LP to MCF-7, U87 and HepG2 cells. Results: The prepared CaAs-LP were spherical and well-dispersed with particle size of (117.16 ± 1.94) nm. The encapsulation efficiency and the drug loading rate of CaAs-LP were (74.31 ± 2.11)% and (8.31 ± 0.13)%, respectively. In vitro release studies showed that CaAs-LP had the characteristics of sustained release and pH sensitive drug release, which can achieve specific drug release in the tumor environment. The carrier displayed remarkable biocompatibility in MCF-7, U87, HepG2 and L02 cells. MTT assay showed that the median lethal concentrations (IC50 values) of MCF-7, U87 and HepG2 cells were 11.91, 4.90 and 19.41 μmol/L, while L02 was 27.59 μmol/L, respectively, which showed strong inhibiting effect on tumor cells. Conclusion: CaAs-LP reveals significantly sustained and pH sensitive release characteristics. CaAs-LP is a potential drug delivery system against solid tumor with tumor micro-environment responsive.
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Objective: To optimize preparation of mitochondrial targeting hyperoside liposomes (DLD/Hyp-Lip), and study its stability in fetal bovine serum, in vitro release behavior and mitochondrial targeting. Methods: DLD/Hyp-lip was prepared by film dispersion method. Single factor experiment was carried out with entrapment efficiency and drug loading as indexes to investigate the effects of the ratio of phospholipids to hyperoside (Hyp) and DSPE-PEG (distearoyl phosphoethanolamine-polyethylene glycol) to DLD on DLD/Hyp-Lip. The formulation of DLD/Hyp-Lip was further optimized by central composite design response surface methodology. The appearance, size and potential of liposomes were observed by transmission electron microscope and particle size analyzer. The stability and drug release rate of liposomes in fetal bovine serum were evaluated by serum stability test and in vitro drug release test. The drug delivery system was evaluated by mitochondrial targeting. Results: The optimal formula of DLD/ Hyp-Lip was as follows: the ratio of total phospholipids to hyperoside was 12.50:1, the ratio of total phospholipids to cholesterol was 6.00:1, and the dosage ratio of DSPE-PEG to DLD was 3:5, the encapsulation efficiency was (95.57 ± 0.56) %, the drug loading was (8.55 ± 0.57) %. The prepared liposomes had good appearance, the particle size of the lip was (124.9 ± 3.4) nm, and the potential was (-6.2 ± 1.9) mV. It was stable in fetal bovine serum and accumulated in vitro release medium for 24 h. Mitochondrial targeting experiments showed that DLD/Hyp-Lip could promote the accumulation of drugs in the mitochondria. Conclusion: This method is simple and convenient, and can accurately and effectively optimize the preparation process of DLD/Hyp-Lip. The prepared DLD/Hyp-Lip has high encapsulation efficiency, small particle size, uniform distribution and good sustained-release effect, which lays the foundation for further in vivo research of DLD/Hyp-Lip. DLD/Hyp-Lip with hyperoside has good mitochondrial targeting of liver cancer cells and is a potentially efficient mitochondrial targeted drug delivery system for liver cancer cells.
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Objective: In view of druggability issue of limonin (LM), the liposomal preparation was developed. The liposomal formulation and preparation process were optimized, and its in vitro antitumor activity was investigated. Methods: In this study, LM was loaded in liposomes to increase its stability and solubility. Meanwhile, in vitro cytotoxicity of LM@Lip was evaluated. LM@Lip were prepared by thin-film dispersion method, and formulation selection and process optimization were operated by single factor and orthogonal experiment. Size distribution, PDI and zeta potential were measured by Malvern sizer, and the encapsulation efficiency and drug loading content were determined by HPLC. The dialysis method was used to investigate the release profile of LM@Lip. In vitro cytotoxicity against HepG2 and A549 cells were estimated by MTT method. Results: The optimized preparation conditions of liposomes were as follows: drug/lipid ratio was 1:150, cholesterol/lipid ratio was 1:9, the ultrasonic power was 120 W for 6 min (1 s interval). The average particle size, PDI and Zeta potential of optimized LM@Lip were (119.5 ± 6.2) nm, 0.318 ± 0.124, (-17.2 ± 1.3) mV, respectively, and the encapsulation efficiency and drug loading content were 87.9% and 0.57%. The final concentration of LM was 63.4 μg/mL. The release results showed 58.59% drug was released in 12 h. MTT results showed that the IC50 of LM@Lip on HepG2 and A549 cells was 20.16 and 15.39 μg/mL, respectively, and its in vitro antitumor was superior to that of LM. Conclusion: Liposomes can increase the stability and solubility of LM. LM@Lip showed slow-release profile and significant tumor inhibition superior to LM.
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OBJECTIVE： To prepare pogostone transfersomes， and to evaluate its quality. METHODS： Film dispersion method was used to prepare pogostone transfersomes. Using the accumulative penetration volume （Qn） and accumulative penetration ratio （PR） of pogostone as evaluation indexes， the types of surfactant， formulation were screened in respects of the dosage of surfactant and the dosage of pogostone. The pogostone transfersomes were prepared with optimal formulation； the morphology， particle size distribution and Zeta potential were observed and the entrapment efficiency was measured. RESULTS： The optimal formulation was as follows as the sodium cholate was selected as surfactant； the dosage of sodium cholate was 0.25 g； the dosage of pogostone was 15 mg. The optimal pogostone transfersomes were ivory-white suspension； average particle size was （115.6±3.65） nm （RSD＝3.20％，n＝3）； PDI was 0.185±0.008 （RSD＝4.30％， n＝3）； Zeta potential was （－13.76±0.225） mV （RSD＝1.70％，n＝3）； entrapment efficiency of pogostone was （46.01±0.40）％ （RSD＝0.87％，n＝3）； Qn was （378.76±0.61） μg/cm2 （RSD＝0.20％，n＝3）； PR was （89.02±0.96）％ （RSD＝1.10％，n＝3）. CONCLUSIONS： Prepared pogostone transfersomes are in line with quality requirements， which can provide reference for the further study of new dosage form of pogostone.
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Objective: The preparation process of curcumin-loaded TPGS/F127/P123 mixed micelles was optimized with uniform design method to improve the poor solubility of curcumin in water, aiming to increase entrapment efficiency (EE), drug-loading (DL), and reduce the precipitated drug (PD). Methods: Curcumin-loaded TPGS/F127/P123 mixed micelles were prepared by thin-film hydration method with modification. Before using the uniform design, a number of preliminary experiments were conducted to identify the controlled factors such as the amount of curcumin, the dosage of TPGS, and the ratio of F127/P123. The formulation was operated by uniform design of three factors and seven levels, and its results were fitted by polynomial linear equation, the response surface, and the contour line in order to choose and verify the optimal preparation process. Results: In the optimum formulation, the dosage of curcumin was 14.0 mg, TPGS 150.0 mg, and the ratio of F127/P123 was 68: 32. The solubility of optimum formulation was (3.47 ± 0.14) mg/mL, EE (87.15 ± 4.39)%, DL (4.70 ± 0.17)%, and PD (0.33 ± 0.12)% in 48 h. Conclusion: The solubility of curcumin in TPGS/F127/P123 mixed micelles was improved after the optimization of the uniform design method, and EE and DL were also improved.
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Objective To optimize the formulation ratio and preparation process of galactosylated cantharidin liposome (Lac-CTD- lips) and establish its methodology for content determination. Methods The method of determination of GC-MS cantharidin content was established by film dispersion method. The entrapment efficiency of cantharidin was evaluated as an index. The preparation process of Lac-CTD-lips was optimized by single factor and orthogonal experiments. Its surface characteristics, encapsulation efficiency, particle size, and Zeta potential were also investigated. Results The best prescription was as follow: cantharidin: hydrogenated soya lecithin:cholesterol at 1:20:5, 10% galactoside, film-forming at 50 ℃, film cleaning with 30 mL of PBS solution of pH 6.0, and hydartion at 40 ℃ for 1.5 h. The resulting liposomes exhibited a pale blue opalescent appearance, a spherical particle morphology, and a more rounded surface with no adhesion. The average particle size was (123.9 ± 4.8) nm (n = 3), the particle size distribution was single-peak, the zeta potential was (-0.36 ± 0.81) mV (n = 3), and the encapsulation efficiency was over 75%. Conclusion GC-MS is suitable for the determination and analysis of cantharidin content. The optimal preparation technology from orthogonal experiment is stable and reliable. The obtained liposomes have higher encapsulation efficiency, small particle size, and good appearance.
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Objective To explore the preparation technology of celastrol/sodium tanshinone IIA sulfonate-coloaded liposome (Cel/STS-CL) and verify the synergistic anti-breast cancer effects in vitro. Methods The optimal ratio of celastrol to sodium tanshinone IIA sulfonate for synergistic anti-breast cancer effect was explored by MTT assay. The liposome was prepared by conventional film dispersion method. The physiochemical properties and morphology were measured by dynamic light scattering (DLS), HPLC, and transmission electron microscopy (TEM), respectively. Meanwhile, the in vitro synergistic anti-breast cancer effect of liposome was investigated by cellular uptake, antiproliferative assay, and cell apoptosis induction using MCF-7 cells as model. Results Hydrophilic sodium tanshinone IIA sulfonate and hydrophobic celastrol were simultaneously encapsulated into liposomes by film dispersion method. The liposome had a nearly spherical shape with a clear bilayer, as well exhibited the particle sizes of (104.7 ± 2.1) nm, narrow polydispersion index (PDI) of (0.217 ± 0.002), and zeta potential of (-48.8 ± 2.3) mV. The encapsulation efficiency of celastrol and tanshinone IIA sulfonate were (82.2 ± 2.7)% and (66.2 ± 2.3)%, respectively. In cellular studies, the cellular uptake of liposome was 30 times higher than that of control group; The half proliferation inhibitory concentration (IC50) was (1.42 ± 0.12) μmol/L against MCF-7 cells with a combined index as 0.81. Besides, 80% of MCF-7 cells were induced to apoptosis by Cel/STS-CL, which was 0.1 time higher than Cel-Lip. Conclusion The preparation of Cel/STS-CL was feasible and efficiently, and promising for the in vitro synergistic anti-breast cancer effect, as well in the further studies.
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Objective: To prepare curcumin-micelles adopting vitamin E-TPGS (VE-TPGS) and Solutol HS15 (SHS15) as carriers, and study the effect on solubility and oral bioavailability of curcumin (Cur). Methods: Cur was loaded into micelles between VE-TPGS and SHS15 by thin film dispersion method. Particle size, loading efficiency, entrapment efficiency, and in vitro release were carried on to estimate the influence of micelles on Cur; Moreover, oral bioavailability in rats was also evaluated. Results: The particle size was (35.79 ± 1.23) nm with polydispersity index (PDI) of 0.12 ± 0.03 when the optimized micelles ratio was at 3:7 of VE-TPGS and SHS15, which increased the solubility of Cur to 2.03 mg/mL in water. The entrapment efficiency and drug loading were 90.03% and 9.34%, respectively. The in vitro release profile showed a sustained release property compared with that of Cur. In addition, the relative bioavailability of micelles (AUC0~∞) compared with that of Cur (AUC0~∞) was 303.5% (P < 0.01). Conclusion: The Cur-micelles combined use of VE-TPGS and SHS15 shows great potential clinical application.
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Objective: To prepare silybin (SLB) proliposomes and evaluate its quality. Methods: SLB proliposomes were prepared by freeze-drying method, and the formulation and process were optimized by single factor investigation and orthogonal design with the encapsulation efficiency and drug loading as indexes. The optimal cryoprotetant was selected and the morphology, particle size, encapsulation efficiency, and stability of SLB proliposomes were investigated. Results: The optimized preparation process was as follows: The ratio of drug to total lipid was 1:12, the ratio of phospholipid to cholesterol was 4:1, the pH of hydration medium was 7.4 and the temperature was 45℃. Mannitol was the optimal cryprotectant to prepare SLB proliposomes, and the formation of SLB proliposomes looked plumpy and compact. The size of preliposome was around (251.40 ± 2.14) nm, the Zeta potential was around (-30.80 ± 0.89) mV, encapsulation efficiency was (88.92 ± 5.86)%, and it had good stability during storage. Conclusion: The preparation process of SLB proliposomes is simple, and it has high encapsulation efficiency and good stability, therefore, it is deserved to be further studied.
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Objective:To optimize the formula of evodiamine liposomes. Methods:Using phospholipids, cholesterol and vitamin E as the materials, the liposomes were prepared by a film dispersion method. The binomial model of mass ratio of phospholipid to drug, mass ratio of phospholipid to cholesterol and the concentration of phospholipid were fitted by design-response surface methodology using encapsulation efficiency as the index. The formula was optimized by three-dimensional response surface and contour plot. The predic-tive data was validated, and the morphology, particle size and pH were observed. Results:The optimized formula was as follows:the mass ratio of phospholipid to drug was 30. 58∶1, that of phospholipid to cholesterol was 15. 22∶1 and the concentration of phospholipid was 42. 26 mg·ml-1 . The average encapsulation efficiency of evodiamine liposomes was 92. 89%. The appearance was milky white and translucent with round or oval pellets, the particle size was 126 nm and the pH was 6. 94 ± 0. 17. Conclusion: The formula and preparation process of evodiamine liposomes are stable and feasible.
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Objective To research the optimal preparation technology of salinomycin micelle.Methods DSPE-PEG2000 was selected as the carrier.Salinomycin was selected as the model drug.The film dispersion method, the ethanol injection method and the dialysis method were used to prepare salinomycin micelles respectively.The comprehensive evaluation indexes included entrapment rate and drug-loading rate, release capacity and vitro cytotoxicity test in order to select the most suitable preparation technology of salinomycin micelle .Results The film dispersion method is the most suitable preparation technology of salinomycin micelle in the three methods.Its average grain diameter was (14 ±2.3) nm, entrapment rate was (82 ± 2.6)%, drug-loading rate was (6.3 ±2.1)%, IC50 to HepG2 tumor cells was 16.10 ±3.71.Conclusion The film dispersion method of salinomycin micelles has the advantages with the smallest size, the highest entrapment rate and the largest drug-loading rate, which has the function to kill tunmor cells and release slowly.
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Objective: To synthesize brain targeting lipid material [(5-cholesten-3β-yl) (D-glucopyranose-6) sebacate, CHS-SE-GLU] by lipase as catalyst in nonaqueous phase and optimize the preparation technology and formulation of CHS-SE-GLU-modified liposomes. Methods: CHS-SE-GLU was synthesized from CHS-SE prepared in previous work and D-glucose using lipase Novozym 435 in acetone. The structure characterization of the products is obtained by MS and NMR. The CHS-SE-GLU-modified paclitaxel-loaded brain targeting liposomes (GLU-PTX-LP) were prepared by thin film dispersion method. Single factor evaluation was applied to optimizing its preparation technology and formulation. Results: CHS-SE-GLU was confirmed by MS and NMR as target products. The optimal formulation and technology of GLU-PTX-LP were as follows: HSPC as membrane material, the ratio of HSPC to PTX was 0.1, the ratio of CHS to HSPC was 0.5, the dosage of DSPG-Na was 2.5%, hydration time was 0.5 h, and hydration temperature was 50 ℃. Three batches of samples were prepared by optimum preparation process and the average encapsulation efficiency was (93.62±1.34)%, (93.75±1.77)%, (92.04±1.50)%; The average particle size was (89.56±1.35), (92.05±3.42), (104.91±3.71) nm; And the average Zeta potential was (-25.21±0.27), (-26.43±0.44), (-25.17±0.65) mV, respectively. Conclusion: Lipase-catalyzed method for the preparation of brain targeting lipid material is simple and environment friendly with high yield. The entrapment efficiency, particle size, and stability of brain targeting drug-loading liposomes modified by CHS-SE-GLU all meet the requirement, which shows good application prospect.
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OBJECTIVE:To prepare Puerarin polymeric micelles and establish a method to determine its entrapment efficiency. METHODS:Puerarin polymeric micelles were prepared by film dispersion method. The polymeric micelles and free drug were sepa-rated by centrifugal-millipore filter filtration method. The entrapment efficiency of puerarin polymeric micelles was determined by HPLC. Diamonsil C18(2)column was used with 1% citric acid solution-methanol(65∶35)at the flow rate of 1 ml/min. The detec-tion wavelength was set at 250 nm,and column temperature was room temperature. RESULTS:The prepared polymeric micelles were spherical and spherical-like in shape with a mean particle size of 54.12 nm,polydispersity index of 0.122,Zeta potential of -13.60 mV;the linear range of puerarin was 2-10μg/ml(R2=0.999 4)with average recovery rate of 99.2%(RSD=0.9%,n=3). The re-covery rate of free drug was 95.3%(RSD=1.7%,n=3). The mean entrapment efficiency and drug-loading amount of puerarin were(35.5±2.12)% and(0.3±0.07)%,respectively(n=3). CONCLUSIONS:Film dispersion method is suitable for the prepara-tion of Puerarin polymeric micelles. Established method is convenient,accurate and reliable for the content and entrapment efficien-cy determination of Puerarin polymeric micelles.
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OBJECTIVE:To prepare silybin liposomes(SLBL)coated by N-trimethyl chitosan(TMC)(TMC60-SLBL),and to optimize the formula. METHODS:The effects of 3 kinds of preparation methods on encapsulation efficiency of SLBL were com-pared,including film dispersion method,multiple emulsion method and reverse evaporation method. The formula of TMC60-SLBL was optimized by orthogonal test using encapsulation efficiency as index with the concentration of phospholipid,ratio of phospholip-id to cholesterol,ratio of silybin to lipids,hydration temperature as factors. The stability of TMC60-SLBL by optimal formula at 4 and 25℃within 30 d,the particle size and Zeta potential of TMC60-SLBL and SLBL were all compared. RESULTS:The encapsu-lation efficiency of TMC60-SLBL prepared by the film dispersion method was the highest,without statistical significance in encap-sulation efficiency before and after cutting (P>0.05). The optimal formula was with the concentration of phospholipid 6 mg/ml;the ratio of phospholipid to cholesterol 40∶1;the ratio of silybin to lipids 1∶30;the temperature of hydration medium 45 ℃;the encapsulation efficiency were(82.08±2.6)%,RSD=3.17%(n=3). The preparation was stable at 4℃;the mean diameter of SL-BL and TMC60-SLBL were(131.9±1.9)nm and(161.2±2.0)nm,and Zeta potential respectively were(-23.18±1.14)mV and (36.73 ± 2.84) mV. CONCLUSIONS:TMC60-SLBL is prepared successfully,and its formula is simple and practicable with high encapsulation efficiency.
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Objective: To optimize the formulation of Panax notoginseng saponins (PNS) transfersomes and to verify their effects on acute soft tissue injury in rats. Methods: Thin film dispersion method was employed to prepare PNS transfersomes. Based on the elasticity of transfersomes, PNS transfersomal formulation was optimized by a uniform experimental design. Extrusion method and centrifugation-ultrafiltration method were respectively adopted to determine the elasticity and the entrapment efficiency (EE) of PNS transfersomes. The therapeutic effects of PNS transfersomes on acute soft tissue injury in rats were evaluated by observing the indexes of injury symptom, the hemorheology and the histomorphology with Qingpeng Ointment being used as positive control. Results: The optimum formulation was as follows: PNS 100 mg, cholesterol 15 mg, soybean phospholipid 120 mg, vitamin E 2 mg, volatile oils (limonene-citral = 4:1) 80 mg, and hydration liquid (phosphate buffered saline, pH 5.0) 10 mL. The optimized PNS transfersomes had elasticity of (2.74 ± 0.32) min, average size of (123.6 ± 0.36) nm, Zeta potential of (-36.67 ± 2.29) mV, and EE of (82.42 ± 0.69)% and (94.40 ± 0.74)% for ginsenoside Rg1 and ginsenoside Rb1, respectively. The results of pharmacodynamical tests showed that the PNS transfersomes could significantly improve the injury symptom indexes (P < 0.01) and hemorheology (P < 0.05) of the rats compared with model control, and it could also improve their histomorphology. Conclusion: The optimized PNS transfersomes with an appropriate size, desired elasticity, and drug EE are effective for the acute soft tissue injury in rats.
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Objective: To prepare and optimize glycyrrhizic acid bile salt/phosphatidylcholine mixed-micelles fast dissolving sublingual films (GL-BS/PC-MM-FDSFs) and preliminarily evaluate its mucous membrane permeation in vitro. Methods: The formulations of GL-BS/PC-MM-FDSFs were optimized by employing Box-Behnken design-response surface methodology with the amounts of sodium alginate, propylene glycol, and GL-BS/PC-MM as investigation factors, and the disintegration time, cumulative release of drug from the GL-BS/PC-MM-FDSFs within 5 min, and particle size of reconstituted MM from GL-BS/PC-MM-FDSFs as indexes. Mucous membrane permeation test was evaluated in vitro with porcine sublingual mucosa as a model by using Franz diffusion cell. Results: The GL-BS/PC-MM-FDSFs prepared by optimized formulation (23 g/L sodium alginate, 148.5 g/L propylene glycol, and 7.58 mL GL-BS/PC-MM) could fast disintegrate in (22.1 ± 0.7) s, release in vitro at 5 min to (85.30 ± 2.91)%, and the particle size of reconstituted MM from GL-BS/PC-MM-FDSFs was obtained as (146.46 ± 6.42) nm. There was a little deviation between the theoretically predicted value and measured value. It showed that this model had a good prediction. There was no significant difference between the accumulative permeation profiles of GL-BS/PC-MM-FDSFs and GL-BS/PC-MM at each time point. Conclusion: The process that GL-BS/PC-MM is solidified to GL-BS/PC-MM-FDSFs is simple and feasible, and GL-BS/PC- MM-FDSFs could significantly improve the mucous membrane absorption of GL.
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Objective: To study the preparation of sinomenine hydrochloride (SH) loaded nano flexible liposomes and investigate the mechanism of the flexible liposomes for enhanced in vitro transdermal drug delivery. Methods: The SH loaded nano flexible liposomes were prepared by film dispersion method, and the effects of concentration of phosphatidylcholine (PSC), cholesterol (CH), and propyleneglycol (PG) on the entrapment efficiency of SH were also investigated. The SH content was determined by HPLC. The physical property was evaluated by the atomic force microscope (AFM), transmission electron microscope (TEM) and photon correlation spectrometer (PCS). The side-by-side diffusion cells were used to evaluate transdermal delivery of SH by nano flexible liposomes. At the end of the transdermal experiment, the treated skin was carefully observed by scanning electron microscopy (SEM). Results: The SH loaded nano flexible liposomes were prepared by film dispersion method with the PSC (3%), CH (0.02%), and PG (25%); The SH entrapment efficiency was (66±2.3)%. The prepared nano flexible liposomes had a closed spherical or elliptical shape showed by AFM images, the TEM images appeared as multi-lamellar vesicles. The calculated mean size was (170±26) nm, the zeta potential values of -(43±3.4) mV. The SH loaded nano flexible liposomes caused the structure of stratum corneum (SC) layer disturbed and disordered the intercorneocyte domain wider, this increased the skin permeability of drug. Conclusion: The SH loaded nano flexible liposomes are obviously resulted in a remarkable enhancement of the SH transdermal drug delivery, which could act as a new nanodimensional vehicle for transdermal delivery of SH.
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Objective To prepare the long-circulating liposomes of paraoxonase(PON).Methods The long-circulating liposomes of paraoxonase were prepared by film dispersion method.The encapsulation efficiency was determined by gel column.The effects of the factors on the encapsulation efficiency,such as the weight ratio of paraoxonase to phospholipid,cholesterol(Choi) to phospholipid,PEG-cholesterol (PEG-Chol) and the iron strength of water phase,were investigated respectively.Then the formulation was optimized by orthogonal design.Results The encapsulation efficiency of the paraoxonase liposomes was 87.66±3.46%,and the average diameter of the liposomes was about 126 nm.There was no significant change on encapsulation efficiency on 15 d at 4 ℃,and the activity of paraoxonase was maintained basically stable.Conclusion The preparation of PEG-modified paraoxonase liposomes was easy and practicable,and the property investigation in vitro showed that the paraoxonase liposomes were stable.