NERDG 2026
Poster 20 Abstract
Novel Dual-Ligand-Conjugated Hybrid Nanoparticles for Targeted Delivery of Lorlatinib to Lung Cancer Cells
Naveen Rajana, Sravani Ravula, Meghana Mokashi, Mural Quadros, Dhwani Mehta, Carlos A. Sanhueza Chavez, Vivek Gupta
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA
Presenting Author: Naveen Rajana
Corresponding Author: Vivek Gupta, [email protected]
Purpose
Lung cancer is the leading cause of cancer-related deaths worldwide, and in the United States. Lorlatinib is an Anaplastic Lymphoma Kinase (ALK) gene inhibitor and is approved as a first-line treatment for metastatic non-small cell lung cancer (NSCLC). Folate receptors and sialic acid receptors are widely overexpressed in many tumors, including NSCLC, and targeting these receptors will improve treatment efficiency. In this research work, we investigated the anti-cancer efficacy of dual ligand-conjugated Lorlatinib nanoparticles in monolayer and spheroid cultures of lung cancer cell lines.
Methods
The synthesis of ligands was achieved through Carbodiimide chemistry and Steglich esterification reactions, and confirmed by spectroscopic techniques. The Lorlatinib-loaded dual ligand conjugated chitosan-PLGA nanoparticles (LDLNPs) were fabricated using a nanoprecipitation method and optimized using a Box-Behnken design (BBD). The optimized LDLNPs were extensively characterized and evaluated for anti-cancer activity in NSCLC cell lines.
Results
The bond formation between the folic acid (FA) and chitosan (CS) was confirmed by a peak at 8.35 ppm in 1H NMR spectra, suggesting the formation of an amide bond and peaks at 1630 cm− 1, 1560 cm− 1 in ATR-FTIR spectra corresponding to the stretching of the C=O and N–H bending vibration of the secondary amide group. The formation of the ester bond between 4-carboxyphenyl boronic acid (4-CPBA) and poloxamer F-127 (P-F127) was confirmed by the disappearance of the COOH peak near 13 ppm in the NMR spectrum, and a new peak appearing in the FT-IR spectrum at 1724 cm⁻¹, corresponding to the C=O stretching of the ester bond. After completing 18 runs of BBD, the results were analyzed statistically using ANOVA, numerical optimization, and graphical optimization. The particle size, PDI, and zeta potential of the optimized LDLNPs were found to be 210.3±26.4 nm, 0.222±0.01, and -7.2±1.3 mV, respectively. The optimized LDLNPs exhibited an entrapment efficiency of approximately 84.6%±0.4% and a drug loading of 5.6%±0.1%. The IC50 values of lorlatinib, unconjugated NPs, and LDLNPs were found to be 29.9±2.5 µM, 14.6±0.9 µM, and 11.9±0.8 µM, respectively in H460 cells.
Conclusion
We successfully synthesized and characterized the conjugates and fabricated, optimized lorlatinib-loaded, dual-ligand-conjugated chitosan-PLGA nanoparticles for anti-cancer efficacy.
Keywords
Folate receptor; Sialic acid receptors, Hybrid nanoparticles, Spheroid culture, lung cancer
Poster 20 Abstract
Novel Dual-Ligand-Conjugated Hybrid Nanoparticles for Targeted Delivery of Lorlatinib to Lung Cancer Cells
Naveen Rajana, Sravani Ravula, Meghana Mokashi, Mural Quadros, Dhwani Mehta, Carlos A. Sanhueza Chavez, Vivek Gupta
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA
Presenting Author: Naveen Rajana
Corresponding Author: Vivek Gupta, [email protected]
Purpose
Lung cancer is the leading cause of cancer-related deaths worldwide, and in the United States. Lorlatinib is an Anaplastic Lymphoma Kinase (ALK) gene inhibitor and is approved as a first-line treatment for metastatic non-small cell lung cancer (NSCLC). Folate receptors and sialic acid receptors are widely overexpressed in many tumors, including NSCLC, and targeting these receptors will improve treatment efficiency. In this research work, we investigated the anti-cancer efficacy of dual ligand-conjugated Lorlatinib nanoparticles in monolayer and spheroid cultures of lung cancer cell lines.
Methods
The synthesis of ligands was achieved through Carbodiimide chemistry and Steglich esterification reactions, and confirmed by spectroscopic techniques. The Lorlatinib-loaded dual ligand conjugated chitosan-PLGA nanoparticles (LDLNPs) were fabricated using a nanoprecipitation method and optimized using a Box-Behnken design (BBD). The optimized LDLNPs were extensively characterized and evaluated for anti-cancer activity in NSCLC cell lines.
Results
The bond formation between the folic acid (FA) and chitosan (CS) was confirmed by a peak at 8.35 ppm in 1H NMR spectra, suggesting the formation of an amide bond and peaks at 1630 cm− 1, 1560 cm− 1 in ATR-FTIR spectra corresponding to the stretching of the C=O and N–H bending vibration of the secondary amide group. The formation of the ester bond between 4-carboxyphenyl boronic acid (4-CPBA) and poloxamer F-127 (P-F127) was confirmed by the disappearance of the COOH peak near 13 ppm in the NMR spectrum, and a new peak appearing in the FT-IR spectrum at 1724 cm⁻¹, corresponding to the C=O stretching of the ester bond. After completing 18 runs of BBD, the results were analyzed statistically using ANOVA, numerical optimization, and graphical optimization. The particle size, PDI, and zeta potential of the optimized LDLNPs were found to be 210.3±26.4 nm, 0.222±0.01, and -7.2±1.3 mV, respectively. The optimized LDLNPs exhibited an entrapment efficiency of approximately 84.6%±0.4% and a drug loading of 5.6%±0.1%. The IC50 values of lorlatinib, unconjugated NPs, and LDLNPs were found to be 29.9±2.5 µM, 14.6±0.9 µM, and 11.9±0.8 µM, respectively in H460 cells.
Conclusion
We successfully synthesized and characterized the conjugates and fabricated, optimized lorlatinib-loaded, dual-ligand-conjugated chitosan-PLGA nanoparticles for anti-cancer efficacy.
Keywords
Folate receptor; Sialic acid receptors, Hybrid nanoparticles, Spheroid culture, lung cancer
