Comparison of SC to Intramuscular and Intradermal Injections

Although the primary focus of this chapter was to discuss issues associated with SC injection or protein and peptide therapeutics, it is also possible to inject these molecules directly into muscle tissue or into the dermis of the skin. Intradermal (ID) injections are best known for the cosmetic application of collagen (114), while intramuscular (IM) injections are frequently used to administer vaccines. Because of unique biological outcomes, ID injections have also been used successfully for vaccination (115). Although very few direct comparisons have been made, it appears that IM may be superior to ID for vaccination outcomes that have been assessed, but for a few vaccines, ID can be the preferred delivery route (116). This type of assessment, however, is difficult as IM vaccines seem to benefit from the delivery of an adjuvant emulsion system (117) or virus-like particles (118), while the same material may be processed differently following ID delivery. These subjects are outside the scope of this chapter; what is relevant is comparing ID and IM delivery to an SC injection. IM delivery typically results in a delayed-uptake profile and is thus preferred to provide more of a depot delivery relative to an SC injection. ID delivery is perceived to provide a more direct targeting to lymph nodes than SC injection (119).

Many of the parameters listed above for SC injection could also affect PK, PD, and metabolism outcomes of protein and peptide therapeutics administered by IM injection. In the case of vaccination, very few protein or peptide subunit (roughly equivalent to therapeutics for their production, characterization, and formulation issues) vaccines are on the market or in trials (120). Most vaccines are prepared from crude (complex) preparations of nonpathogenic (either by the strain used or by the method of preparation) form of a pathogen that can be prepared cheaply for potential use in developing countries (121). The basic concept of such IM deliveries is to establish a depot where antigen-presenting cells are drawn to process and disseminate antigens. By their complex nature and from this functional paradigm, it is very difficult to appreciate any generalized issues of PK, PD, or metabolism of protein or peptide vaccine components that may be critical for a desirable vaccination outcome.

ID injection lends itself to targeted delivery to antigen-presenting cells that are resident in the dermis: LCs and DCs (122). It appears that physical trauma of the skin, via the activation of innate immune elements, assists in providing a desirable immunological outcome (123). One way to achieve ID delivery is using electroporation to drive materials into the skin (124). Microneedles can also be used to achieve protein or peptide delivery to the dermis (125). An in-depth assessment of transdermal delivery methods for therapeutic proteins and pep-tides is beyond the scope of this discussion.

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