**5. Buccal route**

Delivery of proteins or peptides via buccal route involves administration of therapeutics through the mucosal membrane lining the cheeks [152]. In this process, the drug is placed in the mouth between the gum and cheek [153]. Buccal delivery has many advantages such as ease of use, bypassing the GIT, large contact surface area, etc. This method can also be employed to deliver hydrophilic macromolecules [154]. However, this method has some disadvantages such as irritation of the mucosa, low permeability of the peptide, and bitter taste of many buccal drugs. Absorption enhancers and adhesive polymers are being used to overcome some of these problems. Several drugs such as insulin, oxytocin have been successfully delivered via this route. Mucoadhesion (discussed in Section 2.6) is very important during the development of buccal drug delivery systems. Some methods employed for increased drug delivery via this route are described below.

## **5.1 Absorptions enhancers**

Absorption enhancers are essential for delivering protein or peptide therapeutics, which generally show low buccal absorption rates. Some absorption enhancers are aprotinin, benzalkonium chloride, cyclodextrin, polyoxyethylene, sodium EDTA, etc.

## **5.2 pH**

Permeability of acyclovir was investigated in the presence of sodium glycocholate (absorption enhancer) at a pH range of 3.3 to 8.8. The permeability of acyclovir was found to be pH dependent.

## **5.3 Patch design**

Much research have been performed to understand the relationship between the type and amount of support materials and the drug release profile. Results indicated that these two factors are interrelated. It was also shown that single- and multi-layer patches have different drug release profiles.

## **6. Pulmonary route**

The pulmonary route has been used to successfully deliver peptide therapeutics such as desmopressin, calcitonin, human growth hormone, parathyroid hormone,

etc. [155]. There are several barriers to this route of peptide or protein delivery, such as respiratory mucus, mucociliary clearance, pulmonary enzymes, and macrophages that secrete peroxidases and proteases [156]. However, the large surface area, good vascularization, high capacity for solute exchange, and ultra-thinness are some of the attractive features of the alveolar epithelium that can facilitate systemic delivery of proteins or peptides via this route. The passage of large hydrophilic molecules through alveolar epithelium and capillary endothelium is limited. Absorption enhancers and enzyme inhibitors have been used to increase the absorption of peptide or protein therapeutics. However, these can be damaging to lung tissues. Some pulmonary delivery systems are described below.
