CORNEAL COLLAGEN SHIELD: PHYSICAL PROPERTIES

II. CORNEAL COLLAGEN SHIELD: PHYSICAL PROPERTIES

A. Properties of Collagen The safety of collagen for human use is evidenced by its diverse uses and

biomedical applications. Collagen is a common constituent in soaps, sham- poos, facial creams, body lotions, and food-grade gelatin. In medicine, col- lagen has been used in cardiovascular surgery, plastic surgery, orthopedics, urology, neurosurgery, and ophthalmology. The major medical application of collagen is catgut suture, which is derived from intestinal collagen (7). Twenty-five percent of the total body protein in mammals is collagen; it is the major protein of connective tissue, cartilage, and bone. The secondary and tertiary structures of human, porcine, and bovine collagen are very

Corneal Collagen Shields for Ocular Drug Delivery 311 similar, making it possible to use collagen derived from animal sources in

humans. Biologically, collagen is suggested to promote wound healing (7). Nearly all studies on collagen have shown very low or no immunogenicity (7). Of the 10 collagen types that have been characterized, types 1, 3, and 5 are the most desirable for biomedical applications because of their high biocompatibility and low immunogenicity.

A collagen molecule consists of three polypeptide chains, called a- chains, which form a helix connected by interchain hydrogen bonds. This domain of collagen, called tropocollagen, forms a rodlike unit, 2600–26,000 A˚ in length and 15 A˚ in diameter. The molecular weight of the tropocollagen is 300,000 daltons. Collagen has a characteristic amino acid sequence: gly- cine appears in approximately every third position. Proline and hydroxypro- line make up approximately 25% of the total amino acid content. The hydroxyproline residues are from interchain, noncovalent cross-linkages. Newly synthesized collagen contains only a few cross-linked tropocollagen fibers. However, with increased age, there is an increase in the percentage of cross-linking (7).

In the manufacture of corneal collagen shields, the ability to control the amount of cross-linking in the collagen subunits by exposure to ultra- violet (UV) light is an important physicochemical property, because the amount of cross-linking is related to the dissolution time of the shield on the cornea. Kuwano et al. (8) investigated the effect of collagen cross-linking on ofloxacin bioavailability. In this study, the collagen shields were not impregnated with drug, but drops were instilled after application of the collagen shield. They found the dissolution times for the cross-linked col- lagen shield were longer than those of the non–cross-linked type, thereby prolonging drug delivery times. They concluded that cross-linked collagen shields might be useful ocular drug delivery devices because they can allow drug concentrations to achieve high levels in the cornea and aqueous humor.

B. Properties of Commercial Corneal Collagen Shields The collagen shield was designed to be a disposable, short-term therapeutic

bandage lens for the cornea. It conforms to the shape of the eye, protects the corneal surface, and provides lubrication as it dissolves. Unlike the hydro- philic plastic bandage lenses, the collagen shield offers no refractive benefit; in fact, because it is not optically clear, it reduces visual acuity to the 20/80– 20/200 range. Also, the collagen shield causes some discomfort.

Bio-Cor (Bausch & Lomb Surgical, Inc., Claremont, CA) was the first commercially available shield that was introduced in 1986. The diameter, base curve, oxygen permeability, thickness, water content, and other physi- cochemical characteristics of Bio-Cor collagen shield have been described

312 Higaki et al. Table 1 Comparison of Characteristics of Two Collagen

Shields Brand name

ProShield a SurgiLens b Origin of collagen

Bovine corium Dissolution time (h)

Porcine sclera

Rapid dissolution,

Diameter (mm) 14.0 14.5, 16.0 Base curve (mm)

9.0 ND (8.7–9.5) Dry weight (mg)

Wet weight (mg)

ND

Water content (% H 2 O)

Surface pH

ND

ND = not determined. a Data obtained from Alcon Surgical (Fort Worth, TX). Allergan, Inc.

(Irvine, California) and Oasis have a similar product called KeraShield and SoftShield, respectively.

b Data obtained from Bausch & Lomb Surgical, Inc. (Claremont, CA).

elsewhere (9–11). Bausch & Lomb Surgical, Inc. is selling only SurgiLens now. The shields are derived from bovine collagen and are 14.5 mm in diameter. Dissolution time, determined by UV irradiation during manufac- ture, is about 12 hours (Table 1). The shields are sterilized by gamma- irradiation, then dehydrated and individually packaged for storage and shipping (12). Alcon Laboratories, Inc. (Fort Worth, TX) is selling ProShield. The rapid dissolution as well as 12-, 24-, and 72-hour shields are available. The shields have a diameter of 14 mm and a compound base curve that is approximately 9 mm when hydrated. The water content is approximately 75% (Table 1).