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Objective To optimize the formulation of sinomenine hydrochloride transfersomes (SHTs) and to verify their therapeutic effects on rheumatoid arthritis in rats. Methods SHTs were prepared by ethanol injection method. Their formulation was optimized by an orthogonal test, which was based on the elasticity of transfersomes. Elasticity of transfersomes was measured by constant pressure extrusion method and entrapment efficiency was measured by HPLC combined with centrifugation ultrafiltration. The model of rheumatoid arthritis was established by subcutaneous injection of type II collagen into Wistar rats' tail. The therapeutic effects of the preparation on rheumatoid arthritis in rats were evaluated based on ankle joint score, swelling degree, level of TNF-α and IL-1β in serum as well as histological changes including inflammatory cell infiltration, pannus formation, cartilage destruction, and bone erosion. Results The optimized formulation was as follows: egg phospholipid 300 mg, cholesterol 30 mg, sinomenine hydrochloride 100 mg, sodium deoxycholate 60 mg, vitamin E 5 mg, phosphate buffered saline (pH 8.0) 23 mL, and absolute ethyl alcohol 2 mL. The optimized transfersomes had an average size of (83.31 ± 0.08) nm, Zeta potential of (-32.57 ± 3.27) mV, deformability index of 38.69 ± 1.66, drug content of (2.96 ± 0.27) mg/mL, and entrapment efficiency of (39.82 ± 0.97) %. The results of pharmacodynamical test revealed that the preparation could significantly reduce joint swelling caused by rheumatoid arthritis (P < 0.01) and lower TNF-α and IL-1β level in serum (P < 0.01), effectively alleviate inflammatory response and improve histological changes of ankle joint. Conclusion The preparation process for the transfersomes is feasible and their quality can be controlled. The optimized SHTs are effective for treatment of rheumatoid arthritis in rats.
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Compared with traditional oral administration and parenteral administration, transdermal administration has such fea-tures as convenient application, high local drug concentration and strong security. This paper reviewed the composition, characteristics and applications of new carriers ( microemulsions, ethosomes, transfersomes, niosomes, proliposomes, gels and so on) in transdermal drug delivery system with increased drug transdermal transport efficiency in recent years. The advantages of the new transdermal drug delivery carriers make them possess high research value and broad development space.
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Objective: To clarify the percutaneous absorption characteristics of sinomenine hydrochloride (SIN-HCl) PEGylated transfersomes (SHPT) edge activated by volatile oils and to compare with others carriers. Methods: Various formulations of transfersomes [The representative formulations of SHPT contained different quantity of volatile oils including SHPT-A, SHPT-B, and SHPT-C; non-PEGylated transfersomes (SHT-A and SHT-B) corresponded to SHPT-A and SHPT-B; SHDT was edge activated by sodium deoxycholate], PEGylated liposomes (SHPL), and liposomes (SHLS) were prepared by ethanol injection method. Characterization of vesicles was based on results from particle size, morphology, elasticity, and entrapment efficiency (EE) studies. Elasticity was measured by constant pressure extrusion method and EE was measured by HPLC combined with centrifugation ultrafiltration. The skin permeation test was carried out with a Franz diffusion cell fitted with excised rat skin. The effects of vesicle types (SHPT, SHDT, SHLS, and SIN-HCl aqueous solution), DSPE-PEG 2000, and volatile oil in the SHPT on percutaneous permeation of SIN-HCl were investigated. Results: The SIN-HCl transfersomes and liposomes were mainly unilamellar vesicles with roundish shape and average size of 93-118 nm, without gathering property. The entrapment efficiency was of 11%-40%. The elasticity order of vesicles was SHPT-B > SHDT ≈ SHPT-A > SHT-B > SHT-A ≈ SHPL > SHLS > SHPT-C. The steady-state drug percutaneous permeation rate [J (μg∙cm-2∙h-1)] order of different vesicles was SHT-B (19.10 ± 5.74) > SHPT-B (17.06 ± 0.34) > SHDT (15.16 ± 0.55) > SHT-A (10.96 ± 0.99) > SHPT-A (9.42 ± 1.09) > SHLS (3.90 ± 0.67) > SHPT-C (3.51 ± 0.37) > SIN-HCl aqueous solution (2.26 ± 0.94). The cumulative permeated percentages [Qe (36 h)] of SHT-B and SHPT-B were (89.79 ± 6.67)%, and (84.01 ± 6.77)%, respectively. The Qe (36 h) of SHDT, SHLS, SHPT-C and SIN-HCl aqueous solution were (73.98 ± 10.55)%, (20.29 ± 3.21)%, (15.45 ± 3.04)%, and (10.33 ± 2.91)%, respectively. The lag time of SHPT-A, SHPT-B, SHT-A, SHT-B, and SHDT (0.3-0.6 h) were significantly reduced, compared to SHLS and SIN-HCl aqueous solution (3.5-3.8 h). Conclusion: SHPT edge activated by appropriate volatile oils has good elasticity and percutaneous absorption characteristics, which is better than that of liposomes and transfersomes edge activated by sodium deoxycholate to different degrees.
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Objective: To establish the key conditions for the determination of percutaneous absorption of Panax notoginseng saponins (PNS) in transfersomes (TFS) by in vitro skin permeation method and clarify its percutaneous absorption characteristics. Methods: The film hydration-dispersion method was used to prepare PNS TFS and liposomes (LPS). Their physico-chemical properties were characterized. The drug content and sample volume of PNS TFS for in vitro skin permeation experiments were screened. The effects of vesicle type (TFS or LPS), size of the TFS, and formulation amount of sodium deoxycholate (DOC) on percutaneous permeation of PNS were investigated. Results: The TFS and LPS were mainly unilamellar vesicles with roundish shape and size of (121.2 ± 4.5) and (113.9 ± 2.9) nm, without gathering property. According to the cumulative permeated quantity (Qn) and steady-state percutaneous permeation rate (J) of the assayed ingredients, the appropriate PNS content in the TFS was 500 mg and sample volume was 0.5 mL. Compared with those of the LPS, the Qn values of each assayed component (ginseng saponin Rg1, ginseng saponin Rb1, ginseng saponin Re, PNS R1) in PNS of the TFS were high, and the J values of the assayed components in TFS were about 2-3 times of those in the LPS. The Qn and J values of the assayed components in the TFS with an average size of 120 nm were obviously higher than those of the assayed components in the TFS with an average size of 250 nm. The Qn and J values of the assayed components in PNS TFS with large amount of DOC were prominently higher than those containing small amount of DOC, and the increase ratios of different assayed components were different. Conclusion: In vitro skin permeation method is suitable for the determination of percutaneous absorption of PNS in TFS. The TFS promote drug percutaneous permeation stronger than the LPS and the promotion increases with an appropriate increase of the amount of DOC and decrease of vesicle size of the TFS.
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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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The stratum corneum barrier and the other issues in transdermal drug delivery system have attracted more and more at-tention, and the novel liposomes as the drug delivery vehicles effectively solve the problems. The novel liposomes can significantly im-prove transdermal drug penetration, therefore, can enhance efficacy and shows high application value and development prospects. In the paper, combined with some domestic and foreign current researches, the classification, penetration mechanisms and application of the novel liposomes were reviewed.
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Transport of the drug through skin is best route of drug delivery because of the skin is largest organ human organ with total weight 3 kg and a surface of 1.5 -2.0 m2. Drug carries used in transdermal drug delivery such as liposomes, noisomes, or microemulsions has problem that they remains mostly confined to the skin surface and therefore do not transport drugs efficiently through the skin. By using the concept of rational membrane design we have recently devised special composite bodies, so-called Transfersomes. Transfersomes penetrate through the pores of stratum corneum which are smaller than its size and get into the underlying viable skin in intact form. This is because of its deformable nature. The system can be characterized by in vitro for vesicle shape and size, entrapment efficiency, degree of deformability, number of vesicles per cubic mm. They can act as a carrier for low as well as high molecular weight drugs e.g. analgesic, anesthetic, corticosteroids, sex hormone, anticancer, insulin, gap junction protein, and albumin.
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Objective: To optimize the formulation and prepration of tranexamic acid (TA) transfersomes by central composite design-response surface method. Methods: The transfersomes were prepared using the reverse rotary evaporation method. The effects of phosphatidylcholine (SPC)-cholesterol (CH) ratio, SPC-drug ratio, and the concentration of sodium deoxycholic acid on the entrapment efficiency (EE) were investigated, the results were fitted with binomial equation, and the optimal formulation was predicted by response surface method. Results: The preparation conditions were optimized as SPC-CH (2:1), SPC-drug (6:1), and the concentration of sodium deoxycholic acid 20 mg. Under these conditions, the evaluated EE, drug-loading, average partical size, and Zeta potential of TA transfersomes were (81.28 ± 1.06)%, (4.67 ± 0.28)%, (105.3 ± 7.2) nm, and (-38.5 ± 2.3) mV. The deviation of measured and predicated values was smaller. Conclusion: The central composite design-response surface method is applicable for the optimization of TA transfersomes and the resulting optimal preparation technique is stable and feasible.
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Objective: To investigate the changes of matrine concentration in rat local skin with time after transdermal administration of matrine transfersomes, and to evaluate the transdermal delivery properties. Methods: The matrine transfersomes were applied non-occlusively onto rat skin in vivo with abdominal hair removal, and the concentration of drugs in microdialysate of skin was detected by microdialysis and reverse phase high performance liquid chromatography. Furthermore, the concentration-time curves of matrine in microdialysates of skin were compared among marine transfersomes, liposomes, and deoxysodium cholate solution. Results: After the transfersomes were given to rats, the maximum peak time (tmax) of matrine skin concentration appeared at (4.200 ± 0.447) h. The maximum skin concentration (Cmax) was (0.927 ± 0.251) μg/mL and area under the curve (AUC0-8) was (5.033 ± 1.526) μg·h·mL-1, which were much higher than those of the liposomes and the solution (containing 0.8% sodium deoxycholate, P < 0.05), while tmax shortened much more than that of them. Conclusion: In vivo skin microdialysis could be used to assess the transdermal delivery properties of matrine transfersomes. And matrine transfersomes have the good transdermal permeability and efficacy.
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Liposomes have been widely investigated since 1970 as drug carriers for improving the delivery of therapeutic agents to specific sites in the body. As a result, numerous improvements have been made to make this technology potential the treatment of certain diseases in the clinics. This review mainly focused on various aspects related to the vesicular system, including method of preparation, stabilization, drawbacks, and applications. Various types of vesicular systems such as liposomes, niosomes, transfersomes, pharmacosomes, and nanoparticle have been discussed briefly along with some other emerging vescicular systems (photosomes, archaesomes, genosomes, cryptosomes, discomes) focusing on cell specific gene transfer, photodynamic therapy and ligand mediated drug targeting. Present applications of the liposomes are in the immunology, dermatology, vaccine adjuvant, eye disorders, brain targeting, infective disease and in tumour therapy. The new developments in this field are of specific binding properties of a drug-carrying liposome to a target cell such as a tumor cell and specific molecules in the body (antibodies, proteins, peptides etc), stealth liposomes which are especially used as carriers for hydrophilic (water soluble) anticancer drugs like doxorubicin, mitoxantrone and bisphosphonate-liposome mediated depletion of macrophages. This review would help researchers working in the area of liposomal drug delivery.
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Objective To prepare sinomenine hydrochloride transfersomes and evaluate their qualities. MethodsThree different preparation methods including film dispersion, reverse phase evaporation, and ethanol injection methods were compared according to the encapsulation efficiency of transfersomes. Uniform design was applied to optimize the formulation and pharmaceutical process of reverse phase evaporation. The particle size, the appearance, the Z-potential, and the stability were also evaluated. ResultsThe transfersomes prepared by reverse-phase evaporation method possessed the highest encapsulation efficiency. The ideal combinations of preparation and formulation were: soya lecithin/sodium cholate was 200/30 mg/mg, chloroform/PBS was 5 mL/mL, pH of PBS was 6.5, added sinomenine hydrochloride was 10 mg. The transfersomes obtained were milky white translucent suspension, with a mean encapsulation efficiency of 62.2%. The shape of their particles was spherical or similar to spherical under microscope, which was smooth and disconglutinated with an average diameter of 96.4 nm, and a Z-potential of-35.93 mV. Aggregation or deposition was not observed after exposure under the temperature of 4 ℃ for 30 d. ConclusionThe preparation process of sinomenine hydrochloride transfersomes is feasible, the quality of obtained transfersomes is stable.It is expected to provide a new preparation for clinical use of sinomenine hydrochloride.