By the turn of this century, the way in which drugs will be taken is likely to be quite different from today. Products produced from genetic engineering and hybridoma are polypeptides that would be degraded in the gastrointestinal tract if taken orally. Injections are impractical for most patients who suffer from chronic diseases. Rectal and vaginal administration suffer from cultural resistance and are not likely to be popular. Although buccal route and nasal sprays have been developed for delivering biotechnology pharmaceticals, inaccurate dosing by these routes is the major disadvantage which prevents them from being widely used. The skin and particularly the eyes, are excellent alternatives.
The specific aims of this study, therefore include the following: 1. To study the systemic and ocular absorption of peptide drugs of various size: Information regarding systemic absorption of peptides through the eyes is almost nonexisting and information of ocular absorption is scarce. Therefore, systemic and ocular absorption of peptide preparations through the eyes will be studied with peptide drugs of various size and molecular weight. 2. To improve nasolacrimal peptide absorption with promoters: It is well known that the majority of chemical drugs instilled in the eyes are absorbed systemically. However, the limitations of nasolacrimal absorption o peptide drugs and the promotion of its absorption promoters can be found to increase system absorption. 3. To demonstrate the biological efficacy of peptide drugs delivered by ocular route: Whether or not sufficient amount of peptide drugs has been delivered into systemic circulation can easily be determined by measuring the biological effects that are induced. For example, insulin to lower blood glucose level; glucagon to induced hyperglycemia; enkephalin to produce analgesia; vasopressin to increase blood pressure; etc. 4. To ensure the safety of drug delivery through the eyes: Local irritation and/or pathological changes that might be induced by peptide delivery through the eyes will be studied carefully over time. Obviously, any peptide delivery system through the eyes has to be devoid of ocular side effects to the eyes and the vision should not be compromised or risked.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007511-03
Application #
3264446
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1989-08-01
Project End
1992-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Texas A&M University
Department
Type
Schools of Medicine
DUNS #
City
College Station
State
TX
Country
United States
Zip Code
77845
Chiou, G C; Li, B H (1993) Chronic systemic delivery of insulin through the ocular route. J Ocul Pharmacol 9:85-90
Chiou, G C; Shen, Z F; Li, B H (1992) Effects of permeation enhancers BL-9 and Brij-78 on absorption of four peptide eyedrops in rabbits. Zhongguo Yao Li Xue Bao 13:201-5
Li, B H; Chiou, G C (1992) Systemic administration of calcitonin through ocular route. Life Sci 50:349-54
Chiou, G C; Shen, Z F; Zheng, Y Q et al. (1992) Enhancement of systemic delivery of met-enkephalin and leu-enkephalin eyedrops with permeation enhancers. Methods Find Exp Clin Pharmacol 14:361-6
Chiou, G C; Shen, Z F; Zheng, Y Q (1991) Systemic absorption of oxytocin and vasopressin through eyes in rabbits. J Ocul Pharmacol 7:351-9
Chiou, G C (1991) Systemic delivery of polypeptide drugs through ocular route. Annu Rev Pharmacol Toxicol 31:457-67