# Injectable sustained local release doxorubicin depot technology– a promising adjuvant to systemic treatment?

## TL;DR

This study explores a new injectable doxorubicin depot that releases the drug locally in tumors, showing high local concentrations and minimal side effects.

## Contribution

The study introduces a novel injectable doxorubicin depot technology with sustained release and high local efficacy.

## Key findings

- The depot released 36% and 48% of doxorubicin at 24h and 48h, respectively.
- Intratumoral injections significantly extended survival in mice with colorectal cancer.
- Local doxorubicin concentrations were several times higher than with systemic administration.

## Abstract

Drug depot technologies that release chemotherapeutics locally in cancerous tissues present an intriguing strategy. This study aimed to assess the feasibility, delivery capacity, and therapeutic efficacy of a thin needle injectable doxorubicin-loaded carbohydrate-ester-based (CarboCell) depot technology. CarboCell was evaluated in three experimental setups: (A) In non-tumorous mice, release kinetics were evaluated 24 h and 48 h after a subcutaneous depot injection. (B) In mice with syngeneic CT 26 colorectal cancer, efficacy was evaluated based on tumour growth control and survival. This was done by two intratumoral injections of 50 µl CarboCell containing 1 mg/mL or 4 mg/mL doxorubicin at 5 days intervals. (C) In ten female pigs, local and distant release of doxorubicin from a 2 mg/mL doxorubicin CarboCell (2 or 4 mL) injected into tibial metaphysis was evaluated using microdialysis in nine tissue compartments. (A) Subcutaneous CarboCell depots demonstrated a sustained release of doxorubicin with (mean ± SEM) 36 ± 13% and 48 ± 20% of the loaded dose being released at 24 h and 48 h time points, respectively. (B) Intratumoral injection effectively controlled tumour growth and markedly extended the median survival time compared to the control group. (C) Doxorubicin peak drug concentrations in the metaphysis were > 0.3 µg/mL and could be quantified at least 10 mm from the application site. The systemic spill-over was minimal. Doxorubicin-loaded CarboCell proved easily administrable, maintaining antitumoral activity, good metaphyseal distribution and providing much higher local concentrations in metaphyseal bone providing high local concentrations in metaphyseal bone with a good distribution and limited systemic exposure.

The online version contains supplementary material available at 10.1007/s13346-025-01841-9.

Doxorubicin-loaded CarboCell has a sustained release of doxorubicin.

The cytotoxic efficacy of doxorubicin is maintained when loaded in CarboCell.

Local doxorubicin concentration after application in CarboCell is several times higher than after systemic administration.

The systemic spill-over after local application of doxorubicin-loaded CarboCell is minimal.

The online version contains supplementary material available at 10.1007/s13346-025-01841-9.