. 2015 Jun 19;17(5):1065–1079. doi: 10.1208/s12248-015-9785-x

Table I.

Design and Features of Tumor-Penetrating Microparticles (TPM) for IP Therapy

Limitations of intravenous formulations	Solutions/improvements offered by TPM
1. Not optimized for IP therapy. Intravenous formulations for systemic administration, usually solutions or suspensions of nano-sized particulates (e.g., paclitaxel in Cremophor micelles, ~13 nm), are rapidly cleared from peritoneal cavity via absorption and lymphatic drainage. This in turn results in the need of frequent treatments and indwelling catheters. 2. No tumor selectivity. Normal and tumor tissues are similarly bathed in drug solution. 3. Local toxicity due to exposure of normal tissues to high drug concentrations (e.g., abdominal pain), and use of indwelling catheter. 4. Limited penetration from peritoneal fluid into tumors. Treatment is ineffective in bulky tumors (>1 cm). 5. Not optimized to control slowly growing tumors. Due to short residence time, slowly growing tumors with low fraction of cycling cells may escape treatment.	1. Designed to optimize pharmacokinetics and pharmacodynamics of IP therapy. The size is optimized (4–6 μm) to retard clearance from peritoneal cavity and to promote wide intracavity distribution. TPM has two components, one to release paclitaxel rapidly and the other slowly, in order to achieve optimized target site pharmacokinetics and pharmacodynamics. 2. Tumor selectivity due to selective adherence to tumor surfaces, and greater susceptibility of tumor cells to tumor priming. 3. Lower local toxicity. Fractionated drug release reduces the host tissue exposure. Sustained release eliminates the need of frequent treatments. 4. Enhanced penetration into inner parts of tumors. TPM offers tumor priming to promote penetration into large tumors. 5. Tumor growth control. The combination of rapid and slow drug presentation offers control of tumors with different growth rates.

Limitations of intravenous formulations

Solutions/improvements offered by TPM

1. Not optimized for IP therapy. Intravenous formulations for systemic administration, usually solutions or suspensions of nano-sized particulates (e.g., paclitaxel in Cremophor micelles, ~13 nm), are rapidly cleared from peritoneal cavity via absorption and lymphatic drainage. This in turn results in the need of frequent treatments and indwelling catheters.
2. No tumor selectivity. Normal and tumor tissues are similarly bathed in drug solution.
3. Local toxicity due to exposure of normal tissues to high drug concentrations (e.g., abdominal pain), and use of indwelling catheter.
4. Limited penetration from peritoneal fluid into tumors. Treatment is ineffective in bulky tumors (>1 cm).
5. Not optimized to control slowly growing tumors. Due to short residence time, slowly growing tumors with low fraction of cycling cells may escape treatment.

1. Designed to optimize pharmacokinetics and pharmacodynamics of IP therapy. The size is optimized (4–6 μm) to retard clearance from peritoneal cavity and to promote wide intracavity distribution. TPM has two components, one to release paclitaxel rapidly and the other slowly, in order to achieve optimized target site pharmacokinetics and pharmacodynamics.
2. Tumor selectivity due to selective adherence to tumor surfaces, and greater susceptibility of tumor cells to tumor priming.
3. Lower local toxicity. Fractionated drug release reduces the host tissue exposure. Sustained release eliminates the need of frequent treatments.
4. Enhanced penetration into inner parts of tumors. TPM offers tumor priming to promote penetration into large tumors.
5. Tumor growth control. The combination of rapid and slow drug presentation offers control of tumors with different growth rates.