Ocular (mucosal) drug delivery of peptide / protein drugs :

Ocular delivery of drugs is typically for the treatment of ocular inflammation, corneal wounds and glaucoma. This route has also been investigated for the systemic delivery of peptides and protein drugs. Mentioned below are few peptides being investigated for ophthalmic delivery.

Examples of peptides and proteins that is potentially useful in ophthalmology:

I. Peptides and proteins that may affect aqueous humor dynamics-

- A trial nutriuretic factor
- Calcitonin gene related factor
- LHRH
- Neurotensin
- Vasoactive intestinal peptide
- Vasopressin

II. Peptides and proteins that have immunomodulatory properties-

- Cyclosporine
- Interferon

III. Peptides and proteins that is associated with inflammation-

- Substance P

IV. Peptides and proteins that affect wound healing-

- Epidermal growth factor
- Eye derived growth factor
- Fibronectin
- Insulin like growth factor
- Mesodermal growth factor

Topical ocular drug delivery using conventional dosage forms such as solutions, suspensions and ointments is relatively inefficient with less than 10% of an applied dose being delivered across the cornea into the eye. Besides diffusion barriers the enzymatic barriers also play a very important role.

Contact lens sustained-release drug delivery systems are currently under investigation. Ocular drug bioavailability is known to be very poor. It is estimated that 95% of medication delivered by eye drops is lost as the medication mixes with tears and drains into the nasal canal (in-Pharma Technologist.corn, 2005, January). This medication delivery method is wasteful and can lead to unwanted local and systemic side effects. New drug delivery systems are being developed using polymers in contact lens, which hold therapeutic agents within their matrices to increase drug bioavailability to the eye. As the contact lens comes in contact with the eye, channels open that permit sustained drug delivery (Young, 2004).

Researchers in Singapore have developed a new contact lens ophthalmic drug delivery system that has the ability to control the flow of drug by varying the width of the channels. In this manner, the drug delivery rate can be controlled and the drug remains effective for longer periods. Because the lenses are made in a one-step process, cost of manufacture is kept low. Potential applications include medication delivery for a range of eye diseases, including glaucoma, a leading cause of blindness that is currently difficult to treat, and loading wound-healing drugs in the lenses to treat corneal wounds. The lens material can also be modified to produce self-lubricating contact lenses to relieve the discomfort of contact lens wearers suffering from dry eyes (Alvarez-Lozano, Hiratani, & Concheiro, 2006; in-Pharma Technologist, 2005).
The transport of administered peptides and protein drugs across ocular barriers is mainly limited by proteinases such as neutral protease and aminopeptidase.

Despite the feasibility of systemic absorption of peptides from topically applied ophthalmic solutions, the ophthalmic route of peptide delivery is unlikely to be accepted -at least at the present. This is primarily because of the innate aversion to instilling drugs into the eye and because of the perceived sensitivity of the eye, notably the corneal epithelium, to external insult such as when penetration enhancers are included in a formulation to promote absorption of peptides.

In the next chapter, let us discuss mucosal DDS by the rectal route.

For an expert opinion on formulation development of peptide/ protein molecules http://www.drshrutibhat.com

My other blog that might be of interest- http://www.qa-expert.com/