Pharmacokinetics analysis of sustained release hGH biodegradable implantable tablets using a mouse model of human ovarian cancer.
This paper presents the pharmacokinetic of human growth hormone (hGH) implantable tablets tested on a human ovarian cancer mouse model. In order to obtain a sustained release device which permits to administer a high dose of the hormone that keeps its integrity and stability, three different formulations of hGH-poly (d,l-lactic-co-glycolic acid) (PLGA) were elaborated by direct compression method varying hormone load, PLGA content and compactation time. In vitro studies showed that drug release was mainly controlled by hormone load. Pharmacokinetic studies were conducted by using immunodeficient female mice. Four days before the insertion of hGH implantable tablets in the peritoneal cavity, every mouse received 5x10(6) human ovarian cancer cells (SKOV3.ip1). Hormone serum levels were monitored through bleeding from eye orbital vessels. The population pharmacokinetic model used was based on the in series tank model and model parameters were estimated using the maximum likelihood method. The null hypothesis test about differences between formulations leads us to the conclusion that the three formulations showed the same kinetic behavior except for the hGH load. The hormone release was extended all over 2 weeks but no increase or decrease in survival time was observed. These results suggest that hGH serum levels do not facilitate tumoral cells proliferation, an expected effect of hGH and this could explain why survival times of mice treated with implantable tablets are not shorter than those treated with the control ones.
Santoveña
Ana
A
Departamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200 La Laguna, Tenerife, Spain. ansanto@ull.es
Fariña
José B
JB
Llabrés
Matías
M
Zhu
Yonglian
Y
Dannies
Priscilla
P
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004343:Drug Implants; D004355:Drug Stability; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D016013:Likelihood Functions; D051379:Mice; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000401:mortality / Q000503:physiopathology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015996:Survival Rate; D013607:Tablets; D013997:Time Factors
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D013607:Tablets; D019382:Human Growth Hormone; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid