Targeted delivery of an anti-cancer agent via steroid coupled liposomes.
In the present investigation, testosterone (T) was evaluated as a targeting ligand to direct the site-specific delivery of 5-Fluorouracil (5-FU) bearing liposomes to the androgen receptor (ARs) positive tumors and other organs like prostate, brain, and testis. The testosterone was conjugated with the distearoyl phosphatidyl ethanolamine (DSPE) and then this lipid conjugate, Testosterone-DSPE (T-DSPE) was used as one of the components of the liposome. The liposomes were prepared by cast film method using T-DSPE, egg PC, and cholesterol. Further these liposomes were characterized for vesicle shape, average size, polydispersity index, drug entrapment, and in vitro drug release. It was observed that the prepared liposomes were spherical in shape with an average size of 232 +/- 21 nm and 0.181 +/- 0.064 polydispersity index. The in vitro drug release study showed 79.50 +/- 2.81 percent drug release in 24 h. In vivo performance of the developed liposomes was evaluated using organ distribution study in male albino rats. Moreover the fluorescent microscopy was also performed using 6-Carboxyfluorescein (6-CF) as a fluorescent marker. The organ distribution and fluorescent uptake studies confirm that T-DSPE coupled liposomes were effectively taken up by various ARs expressing tissues. Thus, it may be concluded that the testosterone may be used as an effective ligand for the site-specific delivery of anti-cancer agents to various ARs positive carcinomas.
Mishra
Pramod K
PK
Department of Pharmaceutical Sciences, UTD, SAGAR, India.
Gulbake
Arvind
A
Jain
Aviral
A
Vyas
Suresh P
SP
Jain
Sanjay K
SK
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008024:Ligands; D008081:Liposomes; D008297:Male; D015394:Molecular Structure; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry* / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism; D012995:Solubility; D013739:Testosterone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008024:Ligands; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011944:Receptors, Androgen; D013739:Testosterone; D005472:Fluorouracil