High systemic availability of core-crosslinked polymeric micelles after subcutaneous administration

Area of Science:

• Polymer Chemistry
• Nanomedicine
• Pharmacokinetics

Background:

• Core-crosslinked polymeric micelles (CCPM) offer improved drug delivery.
• Intravenous (IV) administration is common but requires healthcare professional intervention.
• Subcutaneous (SC) administration allows for self-administration and potential cost reduction.

Purpose of the Study:

• To evaluate the pharmacokinetic profile and systemic availability of drug-loaded CCPM after SC injection.
• To compare SC administration with traditional IV administration for CCPM.

Main Methods:

• Dexamethasone (DMS) and paclitaxel (PTX) were covalently attached to CCPM using different linkers.
• Pharmacokinetic studies were performed in mice following single IV or SC doses.
• Drug concentrations in blood were measured over time to determine systemic availability (AUC).

Main Results:

• SC injection of DMS-CCPM yielded approximately 30% systemic availability, comparable to IV administration.
• SC injection of PTX-CCPM resulted in about 40% systemic availability, with drug detected for at least 3 days.
• SC administration of CCPM demonstrated significantly higher systemic availability than other reported nanoformulations.

Conclusions:

• Subcutaneous administration of drug-loaded CCPM achieves high systemic availability.
• This route offers a promising, patient-friendly, and potentially cost-effective alternative to IV delivery for nanomedicines.