Translational research program utilizing the rHDL drug delivery platform.

Date
2019-03-05
Authors
Lacko, Sangram
Sabnis, Nirupama
Mooberry, Linda
Nair, Maya
Dossou, Akpedje
Remaley, Alan
Dossou, Akpedje
Sood, Anil
McConathy, Walter
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Translational research program utilizing the rHDL drug delivery platform. Sabnis N1, Raut S1, Mooberry L1, Nair M1, Nagarajan B1, Garud A1, Dossou A1, Remaley A2, Graham J3 , Sood AK4, McConathy WJ1, Lacko AG1. UNTHSC1, NIH/NHLBI2, Qana Therapeutics3, MD Anderson Cancer Center4. Purpose. Due to the off-target effects, frequently observed with cancer chemotherapy, we established the Lipoprotein Drug Delivery Research Laboratory nearly 20 years ago, to develop a tumor selective drug delivery model, applicable to the transport of drugs with poor solubility and bio-availability. Our purpose was to produce drug formulations with increased therapeutic efficacy, including low off target toxicity Methods We employed two formulations: Synthetic/reconstituted high density lipoprotein formulation (rHDL), resembling native (circulating) HDL, containing the main protein component of HDL, apolipoprotein A-I (apo A-I). rHDL formulation using a 37 amino acid peptide (a mimetic of apo A-I), conjugated to Myristic acid (MYR-5A). Results We developed nano-formulations containing drugs, including paclitaxel, valrubicin, fenretinide, and doxorubicin as well as as well as polynucleotide formulations containing siRNA, pDNA and morpholinos that have been found to be effective against several pre-clinical models of breast cancer, ovarian cancer, prostate cancer, neuroblastoma, Ewing sarcoma and other cancers. Currently we are working on developing novel rHDL formulations for immunotherapy. Our work resulted in over 30 publications in refereed journals, Funding, in excess of $1.5 million from Federal State and private sources, two issued and two pending patents and students graduating with here PhDs and four MSc degrees. Conclusions Currently, both our issued patents are licensed to biotech companies who are actively pursuing the development of our technology. We look forward to and accelerated pace of translating our pre-clinical findings toward commercial and clinical applications.

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