3.6 Ocular and Periodontal Adhesives
Eye drops are a very inefficient delivery method by which to deliver drugs systemi-
cally or locally to humans or animals as they induce a lacrimation reflex. This has
led to the development of a range of solid or semi-solid degradable ophthalmic
inserts and hydrogels, which enable improved contact time with the conjunctiva
(Baeyens et al. 1997 ; Rothen-Weinhold et al. 2000 ). Potential active constituents
comprise antibacterial, anti-fungal, anti-glaucoma and anti-inflammatory agents.
Davis et al. ( 2004 ) have reviewed novel topically-applied corneal epithelium
permeating formulations of carbonic anhydrase inhibitors with cyclodextrins for
glaucoma treatment as well as pro-drug formulations of the antiviral agent, gang-
ciclovir. Recently, a clinical trial for treating canine conjunctivitis used a single
administration to the corneal fornix of bioadhesive ophthalmic inserts of size
5 2 mm, comprising a semi-synthetic carbomer, ethylcellulose, and hydroxypropyl
cellulose soluble polymers. These inserts were impregnated with gentamicin. They
were well accepted by dogs and yielded clinical outcomes of similar efficacy to
gentamicin eye-drops instilled over 20 times in the same treatment period (Baeyens
et al. 2002 ). Other soluble inserts have been based on collagen and chitosan and
these have superior aqueous solubility to semi-synthetic polymers, requiring a
single administration but no removal step (Baeyens et al. 1997 ). An example of
an insoluble insert for glaucoma treatment is an alginate/ethylene vinyl acetate co-
polymer mixture incorporating the anti-muscarinic agent, pilocarpine (Sendelbeck
et al. 1975 ), while pre-formed hydrogels consisting of vinyl pyrrolidone/
methacrylic or acrylic acid co-polymers have been tested in rabbit eyes for the
same drug (Barbu et al. 2005 ). In large animal medicine, diseases such as infectious
bovine keratoconjunctivitis are common and require intervention with antibiotics
administered in formulations and routes ranging from subconjunctival injection to
systemic and topical delivery by spray or ointment (McConnel and House 2007 ). In
all species, ophthalmic topical delivery technologies remain relatively unsophisti-
cated and their efficacy is hindered by tear production, poor corneal permeation and
excessive drainage away from the target site. Nonetheless, localised delivery by
intravitreal injection of anti-VEGF (vascular endothelial growth factor) therapies
for macular degeneration has led to approval of several pioneering gene-based
human medicines (Wolf 2008 ).
Veterinary delivery systems as adjunct treatments for small animal gingivitis and
periodontal disease are based on local application of non-antibiotic and antibiotic anti-
microbial drugs. A biocompatible bioadhesive tablet/hygiene patch (Stomadhex 1 ,
Vetoquinol) releases the antiseptic, chlorhexidine and anti-inflammatory, niacin-
amide over 4 h from a tablet applied to the inside of the lower lip of dogs, resulting in
reduced bacteria levels (Gruet et al. 1995 ). Another example for use in dogs is a CR
flowable biocompatible gel containing doxycycline and N-methyl pyrrolidone
(Doxyrobe 1 , Pfizer Animal Health), which is marketed as a local treatment for
management of periodontal disease (Polson et al. 1996 ; Cleland 2001 ). Bioadhesive
formulations of minocycline have also been tested in dogs and results suggested that
94 D.J. Brayden et al.