Future Technologies to Resolve Medication Noncompliance
BY LEO SEMES, OD, FAAO
Former Surgeon General C. Everett Koop, MD, sagely stated that, “Drugs don’t work in patients who don’t take them.” It is well known that adherence to prescribed regimens for both chronic and acute conditions is notably poor. Topical administration of medications has been the mainstay of therapy for ophthalmic disorders. If there were a means for convenient punctal or continuous dispensing of drugs, then there would be less worry over medication non-adherence.
What’s Available Now
Drug administration reminder apps and sustained ophthalmic drug delivery are two means to assure medication application. The notion of sustained drug delivery has been around for more than a century; contemporary conventional examples include prodrugs, a hydroxypropyl cellulose ophthalmic insert, and emulsion and suspension formulations.
Clearly, each of these examples is not without its drawbacks. The cul-de-sac placement of the hydroxypropyl cellulose plug can be irritating. Emulsions and suspensions can be inconsistent. Given all of this, it is recognized that the half-life on the ocular surface is limited to minutes, while penetration is only fractional for intraocular targets.
What about systemic administration for ocular conditions? The barrier here is that systemic absorption is fraught with potential toxicity just as it is with topical administration.
Nanoparticles and nanocarriers are being investigated for drug delivery to the posterior segment. This conduit overcomes the barriers to penetration and to sustained contact. Applications include gene therapy for inherited blinding diseases (Liu et al, 2011).
Sustained drug delivery of dexamethasone from a punctal plug is also being investigated (Novack, 2016). This has an indication for postsurgical ocular pain and may have application in chronic allergic conjunctivitis.
Extended-release drug formulations for chronic diseases such as glaucoma are being investigated. There is a version of travoprost for reduced dosing intervals (Novack, 2016). These examples suggest that for situational and chronic disorders, the future is bright for improved efficacy.
Recent advances in contact lenses as vehicles for drug delivery have shown that in addition to soaking and molecular imprinting, colloidal nano-laden therapeutic contact lenses via polymeric nano particles, cyclodextrans, liposomes, and microemulsion among small human trials have shown promise. With supra critical fluid technologies, these additives would be applicable to both hydrophobic and hydrophilic contact lenses (Maulvi et al, 2016; Hui and Willcox, 2016).
One other area of interest is corneal cross-linking for the treatment of keratoconus. Barriers to riboflavin application include short resident time on the ocular surface as well as poor penetration due to the lipophilicity of the corneal epithelium. Overcoming these hurdles may lead to applications beyond corneal ectasia, such as modulation of refractive errors.
What’s on the Horizon
While active research over the past half century has produced advances in topical ophthalmic drug administration, future directions to meeting the challenges of topical drug administration will focus on novel molecular means of enhancing contact time, better transport mechanisms, and more convenient intraocular delivery conduits (Yellepeddi and Palakurthi, 2015). CLS
For references, please visit www.clspectrum.com/references and click on document #244.
Dr. Semes is a professor of optometry at the UAB School of Optometry. He is a consultant or advisor to Alcon, Allergan, and Regeneron, and he is a stock shareholder in HPO.