Lung cancer is the leading cause of cancer death in both men and women in the United States. Survival rate of lung cancer patients treated by conventional modalities remains far from satisfactory. Recently, new approaches in the treatment of lung cancer with novel drugs that selectively inhibit tumor blood supply thus controlling cancer cell survival, proliferation and/or metastasis in combination with conventional anticancer or antiangiogenic drugs have generated clinical interest. Our preliminary studies demonstrated that DIM-C-pPhC6H5 (DIM-P), a c substituted diindolylmethanes exhibits antiangiogenic activity. The objective of this proposal is to formulate targeted pegylated CREKA peptide coated nanocarriers of DIM-P (PCNCs-D) and investigate its antitumor activity and antiangiogenic potential for treatment of lung cancer. Our preliminary tube formation assay, western blot and immunohistochemistry studies strongly suggest that DIM-P and PCNCs-D exhibits antiangiogenic activity. Our hypothesis is: targeted pegylated nanocarriers of DIM-P will target tumor blood vasculature and increase plasma half life thereby inhibiting tumor growth by exerting antiangiogenic activity against lung tumors. The novel aspects of this proposal are to study the antiangiogenic efficacy of a novel targeted nanocarrier drug delivery therapy approach using PCNCs-D and to understand the molecular pathways involved in the antiangiogenic effect in an in vivo tumor model. The hypotheses and objectives of the proposed research shall be pursued with the following specific aims: (1) To formulate targeted nanocarriers of DIM-P;(2) To evaluate antiangiogenic and in vivo efficacy of targeted nanocarriers of DIM-P;and (3) To elucidate mechanism pathways involved in PCNCs-D activity in regressed tumors. The results emanating from these studies will demonstrate the usefulness of novel PCNCs-D as an effective targeted delivery of antiangiogenic drug for lung cancer treatment. The proposed studies have strong potential to demonstrate an untested and highly innovative approach for lung cancer treatment.
The objective of this proposal is to formulate targeted pegylated CREKA peptide coated nanocarriers of DIMC-pPhC6H5 (DIM-P) and investigate its antitumor activity and antiangiogenic pathways for treatment of lung cancer. The research proposed in this application is significant because it is expected to provide new data that will lead to significant anticancer activity and decreased adverse reactions than encountered in using multiple chemotherapeutic drugs in lung cancer patients.
|Godugu, Chandraiah; Doddapaneni, Ravi; Singh, Mandip (2017) Honokiol nanomicellar formulation produced increased oral bioavailability and anticancer effects in triple negative breast cancer (TNBC). Colloids Surf B Biointerfaces 153:208-219|
|Chowdhury, Nusrat; Vhora, Imran; Patel, Ketan et al. (2017) Liposomes co-Loaded with 6-Phosphofructo-2-Kinase/Fructose-2, 6-Biphosphatase 3 (PFKFB3) shRNA Plasmid and Docetaxel for the Treatment of non-small Cell Lung Cancer. Pharm Res 34:2371-2384|
|Patel, Ketan; Doddapaneni, Ravi; Sekar, Vasanthakumar et al. (2016) Combination Approach of YSA Peptide Anchored Docetaxel Stealth Liposomes with Oral Antifibrotic Agent for the Treatment of Lung Cancer. Mol Pharm 13:2049-58|
|Godugu, Chandraiah; Doddapaneni, Ravi; Safe, Stephen H et al. (2016) Novel diindolylmethane derivatives based NLC formulations to improve the oral bioavailability and anticancer effects in triple negative breast cancer. Eur J Pharm Biopharm 108:168-179|
|Shah, Punit P; Desai, Pinaki R; Boakye, Cedar H A et al. (2016) Percutaneous delivery of ?-melanocyte-stimulating hormone for the treatment of imiquimod-induced psoriasis. J Drug Target 24:537-47|
|Boakye, Cedar H A; Shah, Punit P; Doddapaneni, Ravi et al. (2015) Enhanced Percutaneous Delivery of 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) Methane for Skin Cancer Chemoprevention. J Biomed Nanotechnol 11:1269-81|
|Patel, Ketan; Chowdhury, Nusrat; Doddapaneni, Ravi et al. (2015) Piperlongumine for Enhancing Oral Bioavailability and Cytotoxicity of Docetaxel in Triple-Negative Breast Cancer. J Pharm Sci 104:4417-4426|
|Boakye, Cedar H A; Patel, Ketan; Singh, Mandip (2015) Doxorubicin liposomes as an investigative model to study the skin permeation of nanocarriers. Int J Pharm 489:106-16|
|Patel, Apurva R; Godugu, Chandraiah; Wilson, Heather et al. (2015) Evaluation of Spray BIO-Max DIM-P in Dogs for Oral Bioavailability and in Nu/nu Mice Bearing Orthotopic/Metastatic Lung Tumor Models for Anticancer Activity. Pharm Res 32:2292-300|
|Patel, Apurva R; Doddapaneni, Ravi; Andey, Terrick et al. (2015) Evaluation of self-emulsified DIM-14 in dogs for oral bioavailability and in Nu/nu mice bearing stem cell lung tumor models for anticancer activity. J Control Release 213:18-26|
Showing the most recent 10 out of 21 publications