Artificial skin, dressing materials and novel drug delivery systems

Artificial skin, dressing materials and novel drug delivery systems Part 3

Novel systems of drug delivery.

Role of bioadhesive polymer systems in enhancing buccal absorption.

Introduction
Even in the present times, it is a tragic statement of fact that for animals, a significant percentage of veterinary treatment protocols involve the delivery of medications via injections. Injections by their very nature, irrespective of their route of delivery, whether intramuscular, intravenous, or subcutaneous are inevitably associated with some degree of pain. Most veterinary practitioners perhaps fondly wish for the day when they could have a painless system of drug delivery.

Transmucosal route
Transmucosal routes of drug delivery are a practitioner's dream while at the same time being a pharmacologist's toughest problem. Some difficult problems in transmucosal routes of drug delivery appear to be in reaching effective concentrations of the drugs in specific tissues. Among the various different transmucosal sites where drugs may be deposited, the mucosa of the oral cavity offers some interesting advantages.

The nasal, rectal, vaginal and ocular route of drug delivery appear to have some distinct disadvantages in that it may be difficult to circumvent the effect of local drug irritation caused at these sites. Once the irritation or sensitization to allergens occurs, irreversible damage to the mucosal lining may be caused. Therefore, great care needs to be exercised while developing a safe and effective vehicle for effective drug delivery.

Oral mucosa
Unique features of the oral mucosa that can hasten absorption of molecules includes the abundant vascularization, rapid recovery time after exposure to stress and the near complete absence of Langerhans cells. The absence of Langerhans cells is especially significant because, this can make the oral mucosa relatively tolerant to potential allergens. Another very significant advantage of using the oral transmucosal route for drug delivery is that this route can effectively bypass the first pass and thus avoid the pre-systemic elimination seen with the gastrointestinal tract.

Three main sites in the oral cavity where drug delivery can be effected are:

The epithelium of the buccal mucosa is about 40-50 cell layers thick, while the sublingual epithelium has a slightly lesser number of cells. It is estimated that the permeability of the buccal mucosa is 4-4000 times greater than that of the skin .

Mucus
Mucus serves as an effective delivery vehicle by acting as a lubricant allowing cells to move relative to one another. Along the same lines, the mucus is also believed to play a role in bioadhesion of mucoadhesive drug delivery systems. At physiological pH, the mucus network carries a negative charge (due to the sialic acid and sulfate residues) which may play a role in mucoadhesion. At this pH mucus can form a strongly cohesive gel structure that will bind to the epithelial cell surface as a gelatinous layer.

Saliva
Another feature of the environment of the oral cavity is the presence of saliva produced by the salivary glands. Saliva protects all fluid tissues of the oral cavity. It protects the soft tissues from abrasion by rough materials and from chemicals. A main reason behind the selection of hydrophilic polymeric matrices as vehicles for oral transmucosal drug delivery systems is the water rich environment of the oral cavity.

Even though the sublingual mucosa is relatively more permeable than the buccal mucosa, it is not suitable for an oral transmucosal delivery system. The sublingual region does not have the rich density of smooth muscle tissue fibers or immobile mucosa, that other regions of the oral cavity have. A constant flowing down of saliva within the oral cavity makes it very difficult for drugs to be retained for a significant amount of time in order to facilitate absorption in this site. The buccal mucosa is more suited for sustained delivery applications, delivery of less permeable molecules, and even peptide drugs.

Buccal Drug Delivery Systems
Polymers which can adhere to either hard or soft tissue have been used for many years in surgery and dentistry. Polymers from many diverse families have been investigated for their potential use as mucoadhesives. These include synthetic polymers such as monomeric acyanoacrylate, polyacrylic acid, hydroxypropyl methylcellulose, and poly methacrylate derivatives as well as naturally occurring polymers such as hyaluronic acid and chitosan . Research on the role of other synthetic polymers such as polyurethanes, epoxy resins, polystyrene, and natural-product cement have also been extensively explored.

Hydrogels
Hydrogels are hydrophilic matrices that absorb water when placed in an aqueous media. They are structured in such a manner that the crosslinking fibers present in their matrix effectively prevent them from being dissolved and thus help them in retaining water. When drugs are loaded into these hydrogels, as water is absorbed into the matrix, chain relaxation occurs and drug molecules are released through the spaces or channels within the hydrogel network. Natural gums and cellulose derivatives also form part of the family of hydrogels. Hydrogels as a source of adhesive preparation for transmucosal drug delivery is an emerging area of importance.

Emerging areas of drug delivery - gene therapy and ultrasound
Other emerging areas of interest include the development of novel drug delivery systems using ultrasound and laser. Gene therapy hopefully will share the same degree of relevance in companion animal and large animal medicine, that it currently enjoys among it's human practitioners.

Conclusion
The search for improved methods of drug delivery continues to remain the focus of attention in pharamcological research endeavours. Improved methods of drug release through transmucosal and transdermal methods would be of great significance in veterinary medicine, as by such routes, the pain factor in drug delivery associated with parenteral routes of drug administration can be totally eleminated.