Contributions
Abstract: EP940
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Nanoparticle delivery systems offer a new approach to increase the effectiveness of treatment and decrease side effects in normal tissues by delivering drugs to the target tissue. Nanoparticle delivery systems have the potential to improve multiple myeloma treatment by increasing specificity and efficacy for example by improving localized concentration in the bone marrow and reducing adverse systemic effects. Furthermore, since orally administered drugs require strict patient compliance, some patient populations can benefit from intermittent dosing and sustained drug release properties. Bone is an advantageous microenvironment for tumor growth in multiple myeloma. Targeting tumor cells within the bone marrow remains a complex challenge due to issues with bone penetration and resistance in the tumor microenvironment.
Aims
Starch is one of the most abundant biomass materials in nature, and is non-toxic, biodegradable, edible, and relatively inexpensive material. The aim of the study was to develop a starch nanoparticle matrix for bone-targeted drug delivery and controlled release of the encapsulated drug for long-acting drug formulations.
Methods
We have previously patented a method for preparing starch nanoparticles (WO2015144983A1) using mechanical high-pressure homogenization at decreased temperatures. The chosen drug pomalidomide was encapsulated inside the starch nanoparticle matrix in situ during the fluidization process. Bone-targeting was achieved by modifying the matrix with alendronic acid. The efficacy of the starch nanoparticle formulations were studied in vitro and in vivo using mouse xenograft models.
Results
In vivo biodistribution of pomalidomide encapsulated with the modified starch nanoparticles showed increased retention and accumulation in the bone microenvironment. A significantly longer survival and decrease in tumor burden was shown when comparing the nanoparticle-delivered pomalidomide with standard oral dosing. Bone strength and volume was additionally improved. Even up to Q3W dosing was achievable using the starch nanoparticle encapsulated pomalidomide.
Conclusion
The starch nanoparticles offer a simple setup of a bio-based, non-toxic matrix for preparing drug nanoparticles without the use of any toxic chemicals. The present study demonstrates that the modified starch nanoparticles maintained a long-acting therapeutic concentration of pomalidomide and decreased tumor burden in the mouse models. Bone microenvironment targeting was achieved by modifying the nanoparticles in situ. The maximum drug loading capacity of the starch nanoparticle formulations was in the range required for a potential human dosing scheme. The presented method is clinically relevant and holds potential to decrease tumor growth in multiple myeloma.
Keyword(s): Myeloma, Nanoparticle
Abstract: EP940
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Nanoparticle delivery systems offer a new approach to increase the effectiveness of treatment and decrease side effects in normal tissues by delivering drugs to the target tissue. Nanoparticle delivery systems have the potential to improve multiple myeloma treatment by increasing specificity and efficacy for example by improving localized concentration in the bone marrow and reducing adverse systemic effects. Furthermore, since orally administered drugs require strict patient compliance, some patient populations can benefit from intermittent dosing and sustained drug release properties. Bone is an advantageous microenvironment for tumor growth in multiple myeloma. Targeting tumor cells within the bone marrow remains a complex challenge due to issues with bone penetration and resistance in the tumor microenvironment.
Aims
Starch is one of the most abundant biomass materials in nature, and is non-toxic, biodegradable, edible, and relatively inexpensive material. The aim of the study was to develop a starch nanoparticle matrix for bone-targeted drug delivery and controlled release of the encapsulated drug for long-acting drug formulations.
Methods
We have previously patented a method for preparing starch nanoparticles (WO2015144983A1) using mechanical high-pressure homogenization at decreased temperatures. The chosen drug pomalidomide was encapsulated inside the starch nanoparticle matrix in situ during the fluidization process. Bone-targeting was achieved by modifying the matrix with alendronic acid. The efficacy of the starch nanoparticle formulations were studied in vitro and in vivo using mouse xenograft models.
Results
In vivo biodistribution of pomalidomide encapsulated with the modified starch nanoparticles showed increased retention and accumulation in the bone microenvironment. A significantly longer survival and decrease in tumor burden was shown when comparing the nanoparticle-delivered pomalidomide with standard oral dosing. Bone strength and volume was additionally improved. Even up to Q3W dosing was achievable using the starch nanoparticle encapsulated pomalidomide.
Conclusion
The starch nanoparticles offer a simple setup of a bio-based, non-toxic matrix for preparing drug nanoparticles without the use of any toxic chemicals. The present study demonstrates that the modified starch nanoparticles maintained a long-acting therapeutic concentration of pomalidomide and decreased tumor burden in the mouse models. Bone microenvironment targeting was achieved by modifying the nanoparticles in situ. The maximum drug loading capacity of the starch nanoparticle formulations was in the range required for a potential human dosing scheme. The presented method is clinically relevant and holds potential to decrease tumor growth in multiple myeloma.
Keyword(s): Myeloma, Nanoparticle