Collagen-based drug delivery and artificial tears.
For patients with conditions requiring chronic rather than acute therapy, the advantages of collagen shields in providing high and sustained levels of drugs and/or lubricants to the cornea are outweighed by the difficulty of insertion of the shield and the problem of blurred vision. We have developed a delivery system in which collagen pieces suspended in a viscous vehicle can be instilled into the lower forniceal space, thereby simplifying application and reducing blurring of vision. The collagen pieces (Collasomes) can be formulated with various constituents such as antibiotics or cyclosporine, or with chemical alterations such as the inclusion of a lipid (Lacrisomes) for the treatment of dry eyes. In the normal eyes of volunteers, Collasomes hydrated in a solution of sodium fluorescein and suspended in a methylcellulose vehicle as a model for delivery of water-soluble drugs produced fluorescein concentrations 17 to 42 times higher in the cornea and 6 to 8 times higher in the aqueous humor, compared with fluorescein-containing vehicle alone. In a preliminary controlled study, 76% of patients with moderately severe keratoconjunctivitis sicca (KCS) preferred Lacrisomes to the vehicle control because of a more soothing effect and longer duration of comfort. All preparations were well tolerated by all study subjects. Current studies involve improving drug delivery by chemically modifying the collagen molecule to slow diffusion of the drug from the Collasome matrix, as well as varying the amount of cetyl alcohol and combining it with modified collagen in Lacrisomes to maximize comfort in patients with dry eyes.
Kaufman
H E
HE
LSU Eye Center, Louisiana State University Medical Center School of Medicine, New Orleans.
Steinemann
T L
TL
Lehman
E
E
Thompson
H W
HW
Varnell
E D
ED
Jacob-LaBarre
J T
JT
Gebhardt
B M
BM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003094:Collagen; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005233:Fatty Alcohols / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007638:Keratoconjunctivitis Sicca / Q000188:drug therapy*; D008297:Male; D008747:Methylcellulose / Q000008:administration & dosage; D008875:Middle Aged; D009883:Ophthalmic Solutions / Q000008:administration & dosage*
D005233:Fatty Alcohols; D009883:Ophthalmic Solutions; D008747:Methylcellulose; D003094:Collagen; C005031:cetyl alcohol