Phase-sensitive polymer-based controlled delivery systems of leuprolide acetate

In vitro release, biocompatibility, and in vivo absorption in rabbits

Somnath Singh, Jagdish Singh

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Leuprolide acetate (LA) is a synthetic analog of gonadotropin releasing hormone. It is effective in prostrate cancer treatment only when its desired concentration in blood is maintained for longer duration. Therefore, the purpose of this study was to investigate the in vitro release, biocompatibility, and in vivo absorption of LA from phase-sensitive polymer delivery systems capable of delivering it at a controlled rate for longer duration. Phase-sensitive formulations were prepared by dissolving dl-polylactic acid (dl-PLA) in a mixture of organic solvents, benzyl benzoate (BB) and benzyl alcohol (BA). LA was incorporated into the polymer solution by homogenization. In vitro release was studied into 15 ml of releasing media contained in a vial which was maintained at 37 °C in a reciprocal shaking water bath. The amount of LA in the released samples was analyzed by stability indicating HPLC method. The biocompatibility of polymer formulations was investigated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vivo absorption of LA from delivery systems was studied in rabbits. Blood samples were analyzed for LA and testosterone contents by commercially available immunoassay kits. In vitro release studies showed a greater release of LA from formulations containing a greater proportion of BA (hydrophilic fraction) in the solvent mixture. In vitro biocompatibility study showed significantly (p <0.05) higher cell viability in growth media diluted with polymer extract than the control. In vivo absorption of LA and its effect on testosterone level in rabbits from the delivery system showed a sustained plasma level of LA up to 12 weeks which suppressed the testosterone plasma concentration to castration level beginning from 14th day until 90 days. Thus, phase-sensitive polymer delivery systems of LA were biocompatible and delivered LA at a controlled rate both in vitro and in vivo to keep testosterone plasma concentration at a castration level up to 3 months.

Original languageEnglish
Pages (from-to)42-48
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume328
Issue number1 SPEC. ISS.
DOIs
StatePublished - Jan 2 2007

Fingerprint

Leuprolide
Polymers
Rabbits
Testosterone
Benzyl Alcohol
Castration
In Vitro Techniques
Baths
Immunoassay
Gonadotropin-Releasing Hormone
Cell Survival

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

@article{a709b33f7eec4afd90144b2f95f6d09a,
title = "Phase-sensitive polymer-based controlled delivery systems of leuprolide acetate: In vitro release, biocompatibility, and in vivo absorption in rabbits",
abstract = "Leuprolide acetate (LA) is a synthetic analog of gonadotropin releasing hormone. It is effective in prostrate cancer treatment only when its desired concentration in blood is maintained for longer duration. Therefore, the purpose of this study was to investigate the in vitro release, biocompatibility, and in vivo absorption of LA from phase-sensitive polymer delivery systems capable of delivering it at a controlled rate for longer duration. Phase-sensitive formulations were prepared by dissolving dl-polylactic acid (dl-PLA) in a mixture of organic solvents, benzyl benzoate (BB) and benzyl alcohol (BA). LA was incorporated into the polymer solution by homogenization. In vitro release was studied into 15 ml of releasing media contained in a vial which was maintained at 37 °C in a reciprocal shaking water bath. The amount of LA in the released samples was analyzed by stability indicating HPLC method. The biocompatibility of polymer formulations was investigated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vivo absorption of LA from delivery systems was studied in rabbits. Blood samples were analyzed for LA and testosterone contents by commercially available immunoassay kits. In vitro release studies showed a greater release of LA from formulations containing a greater proportion of BA (hydrophilic fraction) in the solvent mixture. In vitro biocompatibility study showed significantly (p <0.05) higher cell viability in growth media diluted with polymer extract than the control. In vivo absorption of LA and its effect on testosterone level in rabbits from the delivery system showed a sustained plasma level of LA up to 12 weeks which suppressed the testosterone plasma concentration to castration level beginning from 14th day until 90 days. Thus, phase-sensitive polymer delivery systems of LA were biocompatible and delivered LA at a controlled rate both in vitro and in vivo to keep testosterone plasma concentration at a castration level up to 3 months.",
author = "Somnath Singh and Jagdish Singh",
year = "2007",
month = "1",
day = "2",
doi = "10.1016/j.ijpharm.2006.07.051",
language = "English",
volume = "328",
pages = "42--48",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1 SPEC. ISS.",

}

TY - JOUR

T1 - Phase-sensitive polymer-based controlled delivery systems of leuprolide acetate

T2 - In vitro release, biocompatibility, and in vivo absorption in rabbits

AU - Singh, Somnath

AU - Singh, Jagdish

PY - 2007/1/2

Y1 - 2007/1/2

N2 - Leuprolide acetate (LA) is a synthetic analog of gonadotropin releasing hormone. It is effective in prostrate cancer treatment only when its desired concentration in blood is maintained for longer duration. Therefore, the purpose of this study was to investigate the in vitro release, biocompatibility, and in vivo absorption of LA from phase-sensitive polymer delivery systems capable of delivering it at a controlled rate for longer duration. Phase-sensitive formulations were prepared by dissolving dl-polylactic acid (dl-PLA) in a mixture of organic solvents, benzyl benzoate (BB) and benzyl alcohol (BA). LA was incorporated into the polymer solution by homogenization. In vitro release was studied into 15 ml of releasing media contained in a vial which was maintained at 37 °C in a reciprocal shaking water bath. The amount of LA in the released samples was analyzed by stability indicating HPLC method. The biocompatibility of polymer formulations was investigated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vivo absorption of LA from delivery systems was studied in rabbits. Blood samples were analyzed for LA and testosterone contents by commercially available immunoassay kits. In vitro release studies showed a greater release of LA from formulations containing a greater proportion of BA (hydrophilic fraction) in the solvent mixture. In vitro biocompatibility study showed significantly (p <0.05) higher cell viability in growth media diluted with polymer extract than the control. In vivo absorption of LA and its effect on testosterone level in rabbits from the delivery system showed a sustained plasma level of LA up to 12 weeks which suppressed the testosterone plasma concentration to castration level beginning from 14th day until 90 days. Thus, phase-sensitive polymer delivery systems of LA were biocompatible and delivered LA at a controlled rate both in vitro and in vivo to keep testosterone plasma concentration at a castration level up to 3 months.

AB - Leuprolide acetate (LA) is a synthetic analog of gonadotropin releasing hormone. It is effective in prostrate cancer treatment only when its desired concentration in blood is maintained for longer duration. Therefore, the purpose of this study was to investigate the in vitro release, biocompatibility, and in vivo absorption of LA from phase-sensitive polymer delivery systems capable of delivering it at a controlled rate for longer duration. Phase-sensitive formulations were prepared by dissolving dl-polylactic acid (dl-PLA) in a mixture of organic solvents, benzyl benzoate (BB) and benzyl alcohol (BA). LA was incorporated into the polymer solution by homogenization. In vitro release was studied into 15 ml of releasing media contained in a vial which was maintained at 37 °C in a reciprocal shaking water bath. The amount of LA in the released samples was analyzed by stability indicating HPLC method. The biocompatibility of polymer formulations was investigated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vivo absorption of LA from delivery systems was studied in rabbits. Blood samples were analyzed for LA and testosterone contents by commercially available immunoassay kits. In vitro release studies showed a greater release of LA from formulations containing a greater proportion of BA (hydrophilic fraction) in the solvent mixture. In vitro biocompatibility study showed significantly (p <0.05) higher cell viability in growth media diluted with polymer extract than the control. In vivo absorption of LA and its effect on testosterone level in rabbits from the delivery system showed a sustained plasma level of LA up to 12 weeks which suppressed the testosterone plasma concentration to castration level beginning from 14th day until 90 days. Thus, phase-sensitive polymer delivery systems of LA were biocompatible and delivered LA at a controlled rate both in vitro and in vivo to keep testosterone plasma concentration at a castration level up to 3 months.

UR - http://www.scopus.com/inward/record.url?scp=35348875308&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35348875308&partnerID=8YFLogxK

U2 - 10.1016/j.ijpharm.2006.07.051

DO - 10.1016/j.ijpharm.2006.07.051

M3 - Article

VL - 328

SP - 42

EP - 48

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1 SPEC. ISS.

ER -