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Emodin nanostructured lipid carriers(ED-NLC) were prepared and their quality was evaluated in vitro. Based on the results of single-factor experiments, the ED-NLC formulation was optimized by Box-Behnken response surface method with the dosages of emodin, isopropyl myristate and poloxamer 188 as factors and the nanoparticle size, encapsulation efficiency and drug loading as evaluation indexes. Then the evaluation was performed on the morphology, size and in vitro release of the nanoparticles prepared by emulsification-ultrasonic dispersion method in line with the optimal formulation, i.e., 3.27 mg emodin, 148.68 mg isopropyl myristate and 173.48 mg poloxamer 188. Under a transmission electron microscope(TEM), ED-NLC were spherical and their particle size distribution was uniform. The particle size of ED-NLC was(97.02±1.55) nm, the polymer dispersion index 0.21±0.01, the zeta potential(-38.96±0.65) mV, the encapsulation efficiency 90.41%±0.56% and the drug loading 1.55%±0.01%. The results of differential scanning calorimeter(DSC) indicated that emodin may be encapsulated into the nanostructured lipid carriers in molecular or amorphous form. In vitro drug release had obvious characteristics of slow release, which accorded with the first-order drug release equation. The fitting model of Box-Behnken response surface methodology was proved accurate and reliable. The optimal formulation-based ED-NLC featured concentrated particle size distribution and high encapsulation efficiency, which laid a foundation for the follow-up study of ED-NLC in vivo.
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Portadores de Fármacos , Emodina , Estudios de Seguimiento , Lípidos , NanoestructurasRESUMEN
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： 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: To integrate the toxic component of cantharidin (CTD) into a novel nanostructured lipid carrier (NLC) and optimize the cantharidin nanostructured lipid carrier (CTD-NLC) formulation process to reduce the toxicity of CTD and enhance its targeting. Methods: CTD-NLC was prepared by emulsified ultrasonic dispersion method. The encapsulation efficiency was determined by dialysis method. The average particle size, particle size distribution (polydispersity index, PDI), Zeta potential, encapsulation efficiency, and drug loading were taken as indicators. Univariate investigation and central composite design-response surface methodology (CCD-RSM) were used to optimize the prescription process of CTD-NLC. Multivariate quadratic fitting was used to evaluate the model equation between indicators and factors. The fitted equation was analyzed by the variance analysis and the optimal prescription was predicted by the resonse surface. Results: The optimized CTD-NLC prescriptions were as follow: mass of total lipid was 453.66 mg, solid to liquid lipid ratio of 1:2, total stable dose of 16.9 mg/mL, ratio of Pluronic F68 to egg yolk lecithin (Lipoid E PC S) of 3.88:1, with ultrasound for 30 min (working 2 s, stopping 2 s). The prepared CTD-NLC was clear clarification in appearance with light blue opalescence, the average particle size was (85.99 ± 0.49) nm, PDI was 0.280 ± 0.002, Zeta potential was (-8.21 ± 0.24) mV, encapsulation efficiency was (98.57 ± 0.05)%, and drug loading was (0.65 ± 0.01)%. Conclusion: The fitting model established by CCD-RSM is accurate and reliable. The optimized CTD-NLC distribution is concentrated, with high encapsulation efficiency and good physical stability. It lays a foundation for the subsequent in vitro and in vivo studies of CTD-NLC.
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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: 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 prepare plumbagin transfersomal (PBG-T) gel and investigate its transdermal penetration characteristics in vitro. Methods: Plumbagin transfersomes were prepared by film-ultrasonic dispersion method. The optimal prescription condition of PBG-T was selected by central composite design and response surface method. The formula of PBG-T gel was optimized by orthogonal test. The Franz diffusion cell was used to investigate transdermal penetration characteristics of PBG-T gel in vitro. Results: The optimal prescription condition of transfersomes was determined as drug 10.0 mg, phospholipids 700.0 mg, Tween-80 91.5 mg, ultrasonication time 13 min. The optimal prescription condition of transfersomal gel was 1% carbomer 940 as gel matrix, and 5% glycerol as the humectant. According to the optimized prescription, the entrapment efficiency, the mean particle size, and Zeta potential of PBG-T were (79.88 ± 2.26)%, (125.64 ± 4.54) nm, and (-30.97 ± 1.13) mV. The cumulative penetration rate of PBG-T gel was 70.0% at 12 h. Conclusion: The optimal preparation technique is stable and feasible. Transfersomal gel features a sustained release in vitro, the transfersomal gel can increase penetration rate of plumbagin through the skin of rats.
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Objective To prepare the targeted ursolic acid liposome and evaluate its targeting and inhibitory effects on HeLa cells in vitro. Methods Using folate receptors as cell targets, the new functional targeted material Folate-CONH-PEG-NH-Cholesterol conjugate was synthesized chemically. Ursolic acid liposome was developed by modifying Folate-CONH-PEG-NH-Cholesterol using film dispersed method. The liposome was constructed with calcein as a fluorescent probe marker, and the penetrating ability of targeted liposome on HeLa cells was observed by fluorescence confocal microscopy. The uptake efficiency of targeted liposome was investigated by flow cytometry. Meanwhile, the growth inhibitory effect of ursolic acid liposome on HeLa cells was investigated. Results The targeted ursolic acid liposome prepared by thin dispersion method had obvious targeting effect on HeLa cells and have significant anti-proliferative effect. Conclusion The targeted ursolic acid liposome can effectively penetrate HeLa cells with great killing power on the activity of cervical cancer cells.
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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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This study aimed to prepare andrographolide (AP)-loaded glycyrrhizic acid (GA) micelles (AP-GA)-PMs to enhance the solubility and anti-tumor effect of andrographolide. Firstly, andrographolide (AP) was used as the model drug and glycyrrhizic acid (GA) as carriers to prepare (AP-GA)-PMs. Then the preparation methods and the ratios of drug and carrier were screened and optimized based on particle size, encapsulation efficiency (EE) and loading capacity of micelles. Finally, the pharmaceutical characters and the inhibition rate on HepG2 cells were evaluated on the (AP-GA)-PMs prepared by optimal process. The results showed that the prepared micelles under the optimal process had a nanosize of (127.11±1.38) nm, zeta potential of (-24.01±0.55) mV, the entrapment efficiency rate of (92.01±4.02)% , the drug loading rate of (51.44±1.24)% and high storage stability at 4 °C in 30 d, with slow but highly stable release. Moreover, (AP-GA)-PMs with the IC₅₀ value of 19.25 mg·L⁻¹ had a more synergistic and better anti-tumor effect in comparison with AP (IC₅₀=122.40 mg·L⁻¹) on HepG2 cells (P<0.01). In conclusion, the (AP-GA)-PMs prepared with glycyrrhizic acid as a carrier had a small particle size, large drug loading capacity, and high stability, and could significantly improve the anti-tumor effects of AP.
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Antineoplásicos , Farmacología , Diterpenos , Farmacología , Portadores de Fármacos , Química , Ácido Glicirrínico , Química , Micelas , Tamaño de la Partícula , PolímerosRESUMEN
AIM To prepare nanostructured lipid carriers for volatile oils from Artemisiae argyi Folium.METHODS Heated melting-ultrasonic dispersion method was applied to preparing lipid carriers.Taking solid/liquid lipid ratio,amounts of lipid,emulsifier and volatile oils as influencing factors,and average paticle size as an evaluation index,the formulation was optimized by orthogonal test.With cineole,camphor and borneol as indices,GC-MS was adopted in the content determination of volatile oils.RESULTS The optimal formulation was determined to be 5 ∶ 5 for solid/liquid lipid ratio,1％,3％ and 0.5％ for amounts of lipid,emulsifier and volatile oils,respectively.The obtained clear and transparent lipid carriers demonstrated the average particle size of (72.33 ±1.93) nm,PDI of 0.273 ± 0.004 5,and Zeta potential of (-30.59 ± 1.42) mV,whose in vitro release rate was lower than that of raw medicine within 120 h,along with a higher stability under 4 ℃ than that under 25 ℃.The entrapment efficiencies of cineole,camphor and borneol were 87.49％,86.45％ and 92.12％ with the drug loadings of 8.25％,2.00％ and 3.38％,respectively.CONCLUSION It is suggested that nanostructured lipid carriers for volatile oils from Artemisiae argyi Folium should be stored under 4 ℃ with the features of sustainedrelease and stable physicochemical properties.
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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 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 prepare asiatic acid (AA) loaded chitosan-deoxycholic acid self-assembled micelles (AA-CS-DCA PMs) adopting chitosan-deoxycholic acid (CS-DCA) as carriers and investigate its pharmacokinetic characteristics in rats. Methods AA-CS-DCA PMs were prepared by ultrasonic dispersion method. The characteristics of micelles were evaluated by the distribution of particle size, Zeta potential, drug loading, encapsulation efficiency, and in vitro release. Model of bile drainage was established in conscious rats and pre-column derivatization HPLC method was used to determine the concentration of AA in bile. Moreover, the pharmacokinetics characteristics of AA-CS-DCA PMs in vivo was evaluated by tmax, Cmax and AUC0-t. Results The particle size was (70.5 ± 9.8) nm, the Zeta potential was (38.4 ± 0.8) mV, and encapsulation efficiency and drug loading were (77.8 ± 1.2)% and (11.7 ± 0.2)%, respectively. The in vitro release profile showed a sustained release property. In vivo study showed that Cmax of AA-CS-DCA group (26.05 ± 3.04) μg/h was 2.8 times higher than that of the control group (9.19 ± 1.12) μg/h; The tmax of AA-CS-DCA PMs group prolonged significantly (P < 0.05) in biliary excretion (2 h vs 1 h) and the elimination half-life t1/2 was 1.8 times of the control group [(2.68 ± 1.71) h vs (1.49 ± 0.38 h)]. In addition, the AUC0-24 h which reflected the degree of drug absorption increased by 200% compared with the control group [(99.05 ± 12.83) μg vs (33.56 ± 8.33) μg]. Conclusion The chitosan- deoxycholic acid self-assembled micelles can raise the concentration of AA and prolong the retention time in vivo, which effectively improve the oral bioavailability of AA.
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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.