Intramuscular and subcutaneous drug depot characterization of a long-acting cabotegravir nanoformulation by MALDI IMS
| Autor: | Stephen Castellino, M. Reid Groseclose |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
MALDI imaging
Drug Chemistry media_common.quotation_subject 010401 analytical chemistry Absorption (skin) Pharmacology 010402 general chemistry Condensed Matter Physics 01 natural sciences 0104 chemical sciences Subcutaneous injection chemistry.chemical_compound Cabotegravir In vivo Distribution (pharmacology) Dosing Physical and Theoretical Chemistry Instrumentation Spectroscopy media_common |
| Zdroj: | International Journal of Mass Spectrometry. 437:92-98 |
| ISSN: | 1387-3806 |
| Popis: | Recently, researchers have begun exploring the use of injectable long-acting antiretroviral drug formulations that could improve treatment adherence by offering HIV patients infrequent dosing regimens (≥monthly), which is an attractive alternative to the daily oral dosing that is currently required. These drug nanosuspensions can be injected into patients intramuscularly or subcutaneously to form dissolution-controlled drug depots that deliver therapeutic drug concentrations over extended periods. Despite the potential advantages of long-acting injectables for the treatment of chronic conditions such as HIV infection, the mechanisms driving the in vivo dissolution and absorption profiles of these formulations are not well understood. The objective of this study was to assess the tissue distribution of cabotegravir long-acting (CAB-LA), an injectable antiretroviral medication, in rat intramuscular and subcutaneous injection depots 14-days after a single dose. Tissue sections containing the depots were analyzed by MALDI imaging mass spectrometry (IMS) and the results were correlated with the tissue histology. The data generated by MALDI IMS revealed high levels of cabotegravir (CAB) localized to both the intramuscular and subcutaneous injection depots with diffuse lower relative intensity signals throughout the surrounding tissue. Additionally, targeted high spatial resolution (5 μm pixel dimensions) MALDI IMS experiments revealed a unique distribution for the dipotassium adduct of CAB that was highly localized to multinucleated giant cells (MGCs) surrounding the depot. These data support the premise that the inflammatory tissue response associated with injection of CAB-LA may play an important role in the dissolution, absorption, and systemic distribution of CAB from the injection depots. |
| Databáze: | OpenAIRE |
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