Evaluating parameters affecting drug fate at the intramuscular injection site

Modelling intramuscular drug fate in vitro with tissue-relevant biomimetic hydrogels

“…This ECM is primarily composed of Col1, imparting strength and a framework for interactions with other ECM elements. HA is one of most prominent of these other elements, functioning as a biological lubricant to retain water and minimize friction between fascial layers during dynamic muscle movement ( McCartan et al, 2021 ). Based upon their relative abundance, these ECM components were identified for this initial modelling of the IM injection site.…”

“…Such validation can indeed be conducted using published human PK data from the PharmaPendium database (Elsevier), which contains data for a wide range of IM-approved pharmaceuticals, from small molecules to proteins, in an array of quick or slow releasing formulations. Examples of drugs with such PK data available have been tabulated ( McCartan et al, 2021 ).…”

“…Despite the large number of drugs approved by regulators for IM injection, there is limited knowledge of how these drugs interact with the IM environment, i.e. , drug fate ( McCartan et al, 2021 ). At present there are no standardized in vitro tools available to researchers to investigate IM drug fate for the generation of descriptive pharmacokinetic (PK) data; the development of IM-injected drugs relies heavily on pre-clinical in vivo models, but these in vivo models fail to consistently predict human clinical outcomes ( McCartan et al, 2021 ).…”

“…, drug fate ( McCartan et al, 2021 ). At present there are no standardized in vitro tools available to researchers to investigate IM drug fate for the generation of descriptive pharmacokinetic (PK) data; the development of IM-injected drugs relies heavily on pre-clinical in vivo models, but these in vivo models fail to consistently predict human clinical outcomes ( McCartan et al, 2021 ). Acellular in vitro modelling offers the potential for powerful, in-depth investigations that can address specific drug fate hypotheses in tractable experimental formats ( McCartan et al, 2021 ).…”

“…For such approaches to be of value to pharmaceutical scientists, a tractable model that allowed for the rational addition or exclusion of specific ECM and formulation components is required. Such a model should include components that emulate critical elements of the IM injection site that might control drug binding and a means to monitor drug release from that environment over time under physiologically relevant conditions ( McCartan et al, 2021 ).…”