ABSTRACT
Vincristine (VCR) is mainly used to treat acute lymphocytic leukemia, Hodgkin and non-Hodgkin lymphoma in clinic with definite therapeutic effect. But the obvious neurotoxicity and local stimulation of which limit its clinic use. In order to increase the lymph targeting to enhance the curative effect and to lower the adverse reaction of VCR, the VCR loaded transfersomes (VCR-T) were prepared with dry-film and ultrasonic dispersing methods, and the corresponding pharmaceutical properties, pharmacokinetical characteristics and the targeting ability were studied. The average particle size of VCR-T prepared was 63 nm with an entrapment ratio of 59%. The in vitro transdermal research with modified Franz cell showed that VCR-T permeated through the skin in accordance with polynomial equation, and with an accumulation permeation percentage of 67.4% up to 12 h. An HPLC method was utilized to determine the pharmacokinetics and tissue distribution of VCR. Compared with the iv injection of VCR solution, the retention time of VCR in blood was extended by 12 times with VCR-T, and the targeting index in rat lymph was increased by 2.75 times. As a result, transfersomes could penetrate the skin and enter into the systemic circulation carrying VCR with good lymph targeting ability, which makes it probably a new lymphtic targeting drug delivery system.
Subject(s)
Animals , Male , Rats , Administration, Cutaneous , Antineoplastic Agents, Phytogenic , Blood , Pharmacokinetics , Area Under Curve , Drug Delivery Systems , Liposomes , Chemistry , Lymph Nodes , Metabolism , Particle Size , Rats, Sprague-Dawley , Skin Absorption , Spleen , Metabolism , Surface-Active Agents , Chemistry , Tissue Distribution , Vincristine , Blood , PharmacokineticsABSTRACT
<p><b>OBJECTIVE</b>To study the preparation of liposomes surface-modified with glycyrrhetinic acid targeting to hepatocytes.</p><p><b>METHOD</b>3-succinic-30-stearyl glycyrrhetinic acid(Suc-GAOSt), one of the amphiphilic glycyrrhetinic acid derivatives, was synthesized as targeting molecules, liposomes surface-modified with glycyrrhetinic acid has been produced with ethanol injection method.</p><p><b>RESULT</b>Targeting molecules can be mixed into the liposomal membrane. It was confirmed that the targeting molecules is 9% of the total lipids at the most in the liposomes.</p><p><b>CONCLUSION</b>Liposomes surface-modified with glycyrrhetinic acid was successfully prepared, which is considered to be a potential approach targeting to hepatocytes.</p>
Subject(s)
Drug Carriers , Drug Delivery Systems , Methods , Glycyrrhetinic Acid , Hepatocytes , Liposomes , Particle Size , Phospholipids , Succinic AnhydridesABSTRACT
<p><b>AIM</b>To study the preparation of bovine serum albumin nanoparticles surface-modified with glycyrrhizin(BSA-NP-GL) targeting to hepatocytes.</p><p><b>METHODS</b>The bovine serum albumin nanoparticles (BSA-NP) were prepared by desolvation process. Glycyrrhizin (GL) was oxidized by sodium periodate to be conjugated to surface reactive amino groups (SRAG) of the BSA-NP. The SRAG were quantified by spectrophotometric method using 2, 4, 6-trinitrobenzenesulfonic acid(TNBS). Glycyrrhetinic acid(GA) hydrolyzed from GL, which was on the surface of BSA-NP-GL was assayed by HPLC after isolation by sephadex G-50. Both methods were used to verify the conjugation achieved. HPLC was used to determine surface density of GL on BSA-NP-GL.</p><p><b>RESULTS</b>The amount of SRAG of the BSA-NP-GL decreased by 19.6% compared with normal BSA-NP. The amount of GL molecule was 9.2% of the total determined SRAG of BSA-NP. The mean diameter of the BSA-NP-GL was 73 nm with round shape. The stability of BSA-NP-GL was constant when it was stored at 25 degrees C and 37 degrees C during 10 days.</p><p><b>CONCLUSION</b>BSA-NP-GL was successfully prepared, which is considered to establish an experimental foundation for further research on its ability for targeting to hepatocytes.</p>