This work was directed at obtaining a better gene carrier to improve the effects of gene delivery. Neutral liposomes made from cholesterol, lecithin and DOPE by reverse evaporation technique were used for encapsulating DNA-HAP complex which was made from DNA and optimized HAP. The sizes of complexes and the efficiency of encapsulation were detected. The efficiency of transfection into Hela cells was shown by observation of X-gal staining and measurement of transfection efficience. The average size of complexes was 643nm, the average encapsulating efficiency of DNA in microspheres reached 11.67%. These Lipid-Hydroxyapatite-DNA complex (LHD) could be transfected into mammalian cells. The Lipid-Hydroxyapatite-DNA complex prepared by reverse evaporation technique could be applied availably in DNA delivery system, and it gave another thinking to increase the gene transfection of non- viral genetic vector.
DNA ; administration & dosage ; Durapatite ; administration & dosage ; Genetic Therapy ; Lipids ; administration & dosage ; Transfection ; methods

Nanoparticles had received much attention in the development of new kind of pharmaceutical formation because of the special nano-effectivity. Recently, some studies discovered the special functions of the nanoparticles in transdermal and transmucosal drug delivery systems. Even though the acting mechanism of the nanoparticles in these drug delivery systems are not known, these discoveries of the special function of the nanoparticles provide new developing prospect to the drug delivery systems. This paper mainly reviews the present studying results about the nanoparticles used in the transdermal and transmucosal drug delivery systems, including the lipid nanopaticles, natural polymer and the synthesized polymer nanoparticles.
Administration, Cutaneous ; Animals ; Chitosan ; Drug Delivery Systems ; Humans ; Lipids ; Liposomes ; Nanotechnology ; methods ; Polymers

Various geometric shapes and structures self-assembled of amphiphilic lipids when present in an aqueous environment, as active delivery vehicles, are becoming one of focuses of drug delivery system. Lipid-based cubic liquid crystalline nanoparticles (or Cubosomes) consisting of "honeycombed (cavernous)" structure spontaneously formed when a certain concentration of amphiphilic lipids dispersed in aqueous solution has curved bicontinuous lipid bilayer in three dimensions, separating two congruent networks of water channels. Its unique structure consists of internal double water channels and large interfacial areas, which reveal great flexibility in encapsulation efficiency of various polarities and amount of drugs, and has variegated range of drugs encapsulated. As a drug delivery vehicle, high drug payloads, stabilization of peptides or proteins and simple preparation process are also its advantages. The ability of cubic phase to incorporate and control release of drugs of varying size and polar characteristics, and biodegradability of lipids make it an interesting drug delivery system for various routes of administration, including oral, topical (or mucosal) and intravenous administrations, with extensive application in a multitude of dosage forms. Furthermore, a number of different proteins in cubic phase appear to retain their native conformation and bioactivity, and are protected against chemical and physical inactivation. In this paper, investigations of lipid-based cubic liquid crystalline nanoparticles are reviewed and summarized, with a hope to provide a reference for its in-depth study. At the end, the authors made a development prospect of this novel excellent candidate for active ingredients delivery vehicle.
Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Lipids ; administration & dosage ; chemistry ; Liquid Crystals ; chemistry ; Nanoparticles

The purpose of this study is to investigate the enantioselectivity of norgestrel (NG) transdermal permeation and the potential influence of linalool and lipids on the enantioselectivity. In vitro skin permeation studies of NG across the excised rat skins were performed with Valia-Chien diffusion cells, and the permeation samples were analyzed by enantioselective HPLC. The possible enantioselective permeation of NG across intact rat back skin and lipids extracted rat back skin and the influence of linalool were evaluated. The skin permeation rate of dl-NG was two times higher than that of l-NG when donor solutions (EtOH/H2O 2 : 8, v/v) containing l-NG or dl-NG. It may be mainly attributed to the solubility discrepancy between enantiomer and racemate. The enantioselective permeation of dl-NG across intact rat skin was observed when the donor solutions containing dl-linalool. The permeation flux of l-NG was 22% higher than that of d-NG. But interestingly, the enantioselective permeation of dl-NG disappeared under the same experimental condition except that the lipid extracted rat skin was used. Attenuated total reflection-fourier transform infrared spectroscopy analysis of stratum corneum showed that the wave number for asymmetric CH2 stretching vibrations of lipids treated with dl-linalool was greater than that of the control. The results indicated that the enantioselective permeation of NG may be contributed by the interaction between dl-linalool and lipids. More than half of lipids were composed of ceramides. The stereospecific interaction maybe existed among chiral enhancer (linalool), lipids (ceramides) and/or chiral drugs (NG).
Administration, Cutaneous ; Animals ; Lipids ; pharmacology ; Monoterpenes ; pharmacology ; Norgestrel ; pharmacokinetics ; Rats ; Skin Absorption ; drug effects ; Spectroscopy, Fourier Transform Infrared ; Stereoisomerism

OBJECTIVETo observe the effects of (-)doxazosin(DOX), (+)DOX and (+/-)DOX on serum lipid levels and the mortality rates of the rabbits fed by an atherogenic diet.

METHODSMale white New Zealand rabbits were fed by an atherogenic diet for 4 weeks. 8 rabbits whose serum TC <10 mmol/L were confirmed as normal diet group and were fed normally. 40 rabbits whose serum TC >10 mmol/L were randomly divided into 4 groups (n=10): atherogenic diet group, atherogenic diet with (-)DOX group, atherogenic diet with (+)DOX group and atherogenic diet with (+/-)DOX group, which were intraperitoneally injected with (-)DOX, (+)DOX and (+/-)DOX for 9 weeks respectively. Normal and atherogenic diet group were intraperitoneally injected with double distilled water. After 9 weeks administration of (+/-)doxazosin and its enantiomers, effects of the three agents on serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were observed.

RESULTSThe mortality rate of the rabbits fed by an atherogenic diet for 13 weeks was 40%, and it was much higher than that of the rabbits fed by a normal diet (10%). The mortality rates in the rabbits treated with (-)DOX and (+/-)DOX were lower than that in the rabbits fed by a normal diet (10%). Serum LDL-C level of the rabbits was increased markedly after 4 weeks of atherogenic diet, and it was further increased significantly (P < 0.05 and P < 0.01) during the continued 9 weeks of atherogenic diet. However, serum LDL-C levels were not further increased significantly (P > 0.05) during the continued 9 weeks of atherogenic diet in the rabbits treated with (-)DOX, (+)DOX and (+/-)DOX, respectively.

CONCLUSION(-)DOX and (+/-)DOX increase the survival rate and improve LDL-C disorder mildly in the rabbits fed by an atherogenic diet. The improvements in LDL-C induced by (-)DOX and (+/-)DOX, however, might not be the reason for exploration about the increased survival rate in the rabbits fed by an atherogenic diet.

Animals ; Cholesterol, Dietary ; administration & dosage ; Diet, Atherogenic ; Doxazosin ; pharmacology ; Hyperlipidemias ; blood ; drug therapy ; etiology ; Lipids ; blood ; Male ; Rabbits ; Stereoisomerism

BACKGROUND: To assess the efficacy of fenofibrate treatment in combination with urate lowering agents in patients with gout. METHODS: Fourteen male patients with chronic tophaceous or recurrent acute attacks of gout were evaluated in an open-label pilot study of the hypolipidemic agent, fenofibrate (Lipidil Supra(R) 160 mg/d). Patients were stable on urate lowering agents (allopurinol or benzbromarone) for > or =three months without acute attack for the most recent one month before participating. All patients were being treated with established doses of urate lowering agents without modification throughout the study. Clinical and biochemical assessments including serum uric acid, creatinine, liver function test and fasting serum lipid were measured at (1) baseline (2) after two months of fenofibrate treatment and (3) two months after fenofibrate was withdrawn. RESULTS: Serum uric acid was lowered by 23% after two months of fenofibrate treatment (6.93+/-2.16 vs. 5.22+/-1.16 mg/dL; p=0.016). Triglyceride levels were also reduced after fenofibrate treatment (p=0.001). However, this effect was reversed after the withdrawal (p=0.002) of the drug. Alkaline phosphatase was reduced after fenofibrate treatment (p=0.006), but increased 21% after the withdrawal of the drug (p=0.002). By contrast, serum levels of high density lipoprotein and creatinine were increased 9% (p=0.018) and 12% (p=0.006), respectively; however, both levels were significantly decreased to the baseline levels upon withdrawal of fenofibrate. CONCLUSIONS: Fenofibrate can effectively reduce uric acid levels in addition to its known hypolipidemic effect. Fenofibrate may be used as a potential urate lowering agent in patients with gout, especially in those with coexisting hyperlipidemia.
Uricosuric Agents/*administration & dosage ; Uric Acid/blood ; Procetofen/*administration & dosage ; Middle Aged ; Male ; Lipids/blood ; Humans ; Gout/blood/*drug therapy ; Aged ; Adult

TMZ-SLN were prepared by emulsification-low temperature solidification method with stearic acid. The formulation and the preparation conditions were optimized by orthogonal experiments using entrapment efficiency as the evaluation index. The morphology was detected by transmission electron microscope. The Zeta potentials and the particle size distribution were evaluated by Laser Doppler Anemometry. The entrapment efficiencies and the drug release characteristics in vitro were assessed. The result showed that TMZ-SLN were concinnous and spherical in shape. The mean diameter (d(av) ) was 65.0 +/- 6.2 nm and the Zeta potential was -37.2 mV. The average entrapment efficiency was 58.9% +/- 1.21 %. The drug release behavior in vitro conformed to Higuchi Equation. The formation of a new material phase was testified by analysis of differential scanning calorimetry.
Antineoplastic Agents, Alkylating ; administration & dosage ; chemistry ; Dacarbazine ; administration & dosage ; analogs & derivatives ; chemistry ; Drug Carriers ; chemistry ; Lipids ; chemistry ; Nanoparticles ; chemistry ; Particle Size ; Stearic Acids ; chemistry

OBJECTIVETo prepare four breviscapine lipid carrier gels and general gel, and to study the transdermal promotive effects of them in vitro.

METHODImproved Franz-type diffusion cell and isolated rat skin were used as transdermal barrier, and the transdermal property was fitted by pharmacokinetics equations. The unit area cumulative permeation quantity of breviscapine was determined by HPLC method.

RESULTThe 24 hours' unit area cumulative permeation quantity of SLN gel was the highest, followed in descending order were transfersomal gel, liposomal gel, NLC gel and general gel. The transdermal property in vitro of SLN gel fitted in with Higuchi pharmacokinetics equation.

CONCLUSIONThe lipid carrier gels had different transdermal promotive effects to breviscapine, SLN gel was the best one as breviscapine transdermal carrier.

Administration, Cutaneous ; Animals ; Chemistry, Pharmaceutical ; methods ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Flavonoids ; administration & dosage ; chemistry ; pharmacokinetics ; Lipids ; chemistry ; Male ; Mice ; Skin Absorption

Recently, the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines. However, many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size, resulting in poor absorption and hence poor bioavailability. Nowadays with the advancement in the technology, novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems. For last one decade many novel carriers such as liposomes, microspheres, nanoparticles, transferosomes, ethosomes, lipid based systems etc. have been reported for successful modified delivery of various herbal drugs. Many herbal compounds including quercetin, genistein, naringin, sinomenine, piperine, glycyrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability. The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs (herbal), and to achieve better therapeutic response. An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action (wherever reported) and studies on improvement in drug bioavailability, exhibited particularly by natural compounds.
Biological Availability ; Drug Delivery Systems ; Herbal Medicine ; Humans ; Lipids ; chemistry ; Nanoparticles ; administration & dosage ; chemistry ; Nanotechnology ; Pharmaceutical Preparations ; administration & dosage ; Plant Extracts ; chemistry ; pharmacokinetics ; pharmacology ; Plants, Medicinal ; Solubility

OBJECTIVETo establish a RP-HPLC method for determination of plasma progesterone and to apply the method for pharmacokinetics study of progesterone-loaded lipid nanoparticles after oral administration in rats.

METHODSThe plasma samples were collected from castrated rat after oral administration of progesterone-loaded lipid nanoparticles and extracted by acetic ether. The determination was performed on a Hypersil C18 column (150 mm X 3.9 mm , 5 microm) with a mobile phase consisting of methanol and water (60:40) at a flow-rate of 0.6 ml/min. The UV detector was at 240 nm and danazol was used as internal standard.

RESULTGood linearity was obtained over the range of 0.02-2 microg/ml progesterone in plasma(r=0.9999, n=3). The quantification limit was (0.02 +/-0.004) microg/ml(n=3) and the limit of detection was 0.005 microg.mL(-1)(S/N = or >3). The inter-and intra-day RSDs were all less than 10% for quality control samples at high-, medium- and low-concentrations. The average absolute recovery rate was 90.5 % and the average method recovery was in the range of 93.4 %-107.5%. The plasma concentration-time curves indicated that tmax was delayed after administration of progesterone-loaded lipid nanoparticles, and the bioavailability was increased significantly, compared with contrast solution.

CONCLUSIONThe method developed is stable, simple, rapid, accurate, sensitive and applicable for determining plasma concentrations of progesterone of progesterone-loaded lipid nanoparticles in pharmacokinetic studies.

Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; methods ; Drug Compounding ; Lipids ; chemistry ; Male ; Nanoparticles ; Progesterone ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley