Table 2.

Examples of Considerations When Designing Drug Delivery Strategies for Immunocompromised Hosts

Host Factors		Drug Delivery Factors
Factor	Examples	Factor	Examples
Specific immunodeficiency	-Deficiencies in neutrophils, macrophages, B cells, or T cells -Complex pleotropic host disease states (diabetes, systemic lupus erythematosus, etc.)	Purpose/goal of delivered therapeutic	-Recruitment of immune cells -Stimulation of specific immune phenotype -Replacement of immune function (antibiotic, antibody angiogenic factor, etc.)
Evolution of host immunodeficiency	-Acute immune insult followed by gradual resolution (burn, trauma, etc.) -Chronic immunodeficiency (diabetes, HIV/AIDs, etc.) -Waxing/waning immunodeficiency (need for intermittent chemotherapy, autoimmune disease, etc.)	Spatial delivery requirements	-Systemic versus local delivery -Concentration gradient -Release from the center of the wound to the periphery versus from the periphery to the center
Angiogenic potential	-Vascularization of the wound site -Ability of the host to initiate angiogenesis	Temporal delivery requirements	-Duration of therapy -Release kinetics (Continuous release, burst release, pulse release, etc.)
Presence of pathogens	-“Clean” versus “dirty” wound (for example, tissue loss from resection of a tumor versus tissue loss from a motor vehicle accident) -Proximity to microbiome (skin, oral cavity, gastrointestinal system, genitourinary system, etc.)	Requirement for tissue scaffold and scaffold considerations	-Large versus small defects -Type of scaffold (synthetic polymer, naturally-derived material, composite, etc.) -Scaffold delivery (injection, self-assembly, surgical insertion, etc.)
Other co-morbidities	-Nutritional status -Genetic conditions -Socioeconomic and psychologic burdens of disease, access to healthcare	Immune response to vehicle/scaffold	-Impact on macrophage polarization -Fibrous capsule formation versus tissue incorporation -Response to and clearance of degradation products