Underutilization of the Subcutaneous Route of Administration | Biomed Grid

Therapeutic proteins have become an important part of treatment, particularly for serious and chronic diseases, and the subcutaneous (SC) route of administration has become a more popular, yet still underutilized mode of delivery. The extracellular matrix of the hypodermis is composed of a network of fibrous proteins (e.g., collagen and elastin) embedded within a viscoelastic gel. The viscoelastic gel is composed of glycosaminoglycans and proteoglycans that create resistance to bulk fluid flow in the SC space. The primary glycosaminoglycan is the highly hydrated hyaluronan, a mega-dalton polymer of repeating disaccharide units of N-acetylglucosamine and glucuronic acid. Following SC injection of water-soluble small molecules, absorption into the systemic circulation occurs via local capillaries. In contrast, large molecules (e.g., proteins) reach the systemic circulation via bulk fluid flow into draining lymphatic vessels. Regardless of the size of the injected molecule, current medical dogma suggests that rapid SC injections are limited to a volume of ~2 mL. Injection of volumes of >2 mL are believed to be associated with injection site pain, adverse effects at the injection site (e.g., induration) and injection site leakage [1]. However, there is little evidence from controlled studies to substantiate these assumptions [2]. There are several strategies for overcoming volume restrictions to SC drug administration. Some biologics (e.g., adalimumab) can be concentrated to a sufficient degree to administer an adequate dose in a relatively low volume (<2 mL). Others (e.g., sekukinumab, SCIg) require multiple low volume injections, often across multiple sites, to deliver therapeutic doses. Recently, on-body devices have been developed that are capable of delivering greater volumes (e.g., 10 - 25 mL) very slowly.