2 research outputs found
HPMA-LMA Copolymer Drug Carriers in Oncology: An in Vivo PET Study to Assess the Tumor Line-Specific Polymer Uptake and Body Distribution
Polymeric drug carriers aim to selectively
target tumors in combination
with protecting normal tissue. In this regard polymer structure and
molecular weight are key factors considering organ distribution and
tumor accumulation of the polymeric drug delivery system. Four different
HPMA based copolymer structures (random as well as block copolymers
with lauryl methacrylate as hydrophobic block) varying in molecular
weight, size and resulting architecture were analyzed in two different
tumor models (AT1 prostate carcinoma and Walker-256 mammary carcinoma)
in vivo. Polymers were labeled with <sup>18</sup>F and organ/tumor
uptake was followed by μPET imaging and <i>ex vivo</i> biodistribution. Vascular permeability was measured by dextran extravasation
and vascular density by immunohistochemistry. Cellular polymer uptake
was determined in vitro using fluorescence-labeled polymers. Most
strikingly, the high molecular weight HPMA-LMA random copolymer demonstrated
highest tumor uptake and blood pool concentration. The molecular structure
(e.g., amphiphilicity) is holding a higher impact on desired in vivo
properties than polymer size. The results also revealed pronounced
differences between the tumor models although vascular permeability
was almost comparable. Accumulation in Walker-256 carcinomas was much
higher, presumably due to a better cellular uptake in this cell line
and a denser vascular network in the tumors. These investigations
clearly indicate that the properties of the individual tumor determine
the suitability of polymeric drug carriers. The findings also illustrate
the general necessity of a preclinical screening to analyze polymer
uptake for each individual patient (e.g., by noninvasive PET imaging)
in order to individualize polymer-based chemotherapy
HPMA-LMA Copolymer Drug Carriers in Oncology: An in Vivo PET Study to Assess the Tumor Line-Specific Polymer Uptake and Body Distribution
Polymeric drug carriers aim to selectively
target tumors in combination
with protecting normal tissue. In this regard polymer structure and
molecular weight are key factors considering organ distribution and
tumor accumulation of the polymeric drug delivery system. Four different
HPMA based copolymer structures (random as well as block copolymers
with lauryl methacrylate as hydrophobic block) varying in molecular
weight, size and resulting architecture were analyzed in two different
tumor models (AT1 prostate carcinoma and Walker-256 mammary carcinoma)
in vivo. Polymers were labeled with <sup>18</sup>F and organ/tumor
uptake was followed by μPET imaging and <i>ex vivo</i> biodistribution. Vascular permeability was measured by dextran extravasation
and vascular density by immunohistochemistry. Cellular polymer uptake
was determined in vitro using fluorescence-labeled polymers. Most
strikingly, the high molecular weight HPMA-LMA random copolymer demonstrated
highest tumor uptake and blood pool concentration. The molecular structure
(e.g., amphiphilicity) is holding a higher impact on desired in vivo
properties than polymer size. The results also revealed pronounced
differences between the tumor models although vascular permeability
was almost comparable. Accumulation in Walker-256 carcinomas was much
higher, presumably due to a better cellular uptake in this cell line
and a denser vascular network in the tumors. These investigations
clearly indicate that the properties of the individual tumor determine
the suitability of polymeric drug carriers. The findings also illustrate
the general necessity of a preclinical screening to analyze polymer
uptake for each individual patient (e.g., by noninvasive PET imaging)
in order to individualize polymer-based chemotherapy