NERDG 2026
Poster 23 Abstract
Inhalable Alectinib PLGA Microparticles for ALK-Positive Non-Small Cell Lung Cancer Treatment
Parasharamulu Kommarajula, Varsha Mundrathi, Nitesh Kunda
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA
Presenting Author: Varsha Mundrathi
Corresponding Author: Nitesh Kunda, [email protected]
Purpose
Alectinib is an FDA-approved oral ALK inhibitor indicated for metastatic ALK-positive Non-Small Cell Lung Cancer (NSCLC) and as an adjuvant post-resection therapy in patients with stage IB to IIIA NSCLC. This study investigates local delivery of ALB as an adjuvant therapy, addressing its low oral bioavailability and systemic toxicity. In this study, ALB was incorporated into biodegradable polymer-based microparticles (MPs) and spray-dried into a dry powder for pulmonary administration, enabling targeted delivery to the lungs while minimizing systemic side effects.
Methods
Alectinib microparticles (ALB MPs) were prepared using a single-emulsion solvent evaporation method. The organic phase was prepared by dissolving PLGA and ALB in DCM. This organic phase was then slowly added to the aqueous phase containing a 1% PVA solution. The resulting mixture was then homogenized to form an emulsion. The obtained emulsion was subjected to stirring for the evaporation of DCM. The resultant ALB MPs were separated by centrifugation at 7197 × g at 4°C and washed twice with deionized water to remove unentrapped drug and residual PVA. The final pellet was then redispersed in 5 mL of deionized water. The resulting dispersion was spray-dried using L-Leucine as a carrier via a Buchi B-290 Mini spray dryer to produce a dry powder formulation. The ALB MPs' suspension before spray drying was characterized for particle size and zeta potential using a Malvern Zetasizer. The dry powder formulation was also analyzed for particle size, zeta potential, and solid-state characteristics using DSC, TGA, and pXRD.
Results
The particle size and zeta potential of ALB MPs were 1.31 ± 0.084 μm and -29.93 ± 0.97 mV, respectively. The entrapment efficiency and drug loading were 77.65% and 34.66 μg/mg of the polymer. The spray-dried formulation has also demonstrated a similar particle size, zeta potential, and drug loading with a yield of 57% w/w.
Conclusion
In conclusion, Alectinib microparticles were successfully formulated and spray-dried, resulting in a dry powder suitable for inhalation. This formulation enables the convenient pulmonary delivery of the ALK inhibitor, offering a promising approach for targeted delivery, which maximizes local drug concentration at the target site and reduces systemic exposure and associated side effects.
Keywords
Inhalable PLGA microparticles, Targeted Therapy, ALK-positive, NSCLC, Alectinib
Poster 23 Abstract
Inhalable Alectinib PLGA Microparticles for ALK-Positive Non-Small Cell Lung Cancer Treatment
Parasharamulu Kommarajula, Varsha Mundrathi, Nitesh Kunda
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA
Presenting Author: Varsha Mundrathi
Corresponding Author: Nitesh Kunda, [email protected]
Purpose
Alectinib is an FDA-approved oral ALK inhibitor indicated for metastatic ALK-positive Non-Small Cell Lung Cancer (NSCLC) and as an adjuvant post-resection therapy in patients with stage IB to IIIA NSCLC. This study investigates local delivery of ALB as an adjuvant therapy, addressing its low oral bioavailability and systemic toxicity. In this study, ALB was incorporated into biodegradable polymer-based microparticles (MPs) and spray-dried into a dry powder for pulmonary administration, enabling targeted delivery to the lungs while minimizing systemic side effects.
Methods
Alectinib microparticles (ALB MPs) were prepared using a single-emulsion solvent evaporation method. The organic phase was prepared by dissolving PLGA and ALB in DCM. This organic phase was then slowly added to the aqueous phase containing a 1% PVA solution. The resulting mixture was then homogenized to form an emulsion. The obtained emulsion was subjected to stirring for the evaporation of DCM. The resultant ALB MPs were separated by centrifugation at 7197 × g at 4°C and washed twice with deionized water to remove unentrapped drug and residual PVA. The final pellet was then redispersed in 5 mL of deionized water. The resulting dispersion was spray-dried using L-Leucine as a carrier via a Buchi B-290 Mini spray dryer to produce a dry powder formulation. The ALB MPs' suspension before spray drying was characterized for particle size and zeta potential using a Malvern Zetasizer. The dry powder formulation was also analyzed for particle size, zeta potential, and solid-state characteristics using DSC, TGA, and pXRD.
Results
The particle size and zeta potential of ALB MPs were 1.31 ± 0.084 μm and -29.93 ± 0.97 mV, respectively. The entrapment efficiency and drug loading were 77.65% and 34.66 μg/mg of the polymer. The spray-dried formulation has also demonstrated a similar particle size, zeta potential, and drug loading with a yield of 57% w/w.
Conclusion
In conclusion, Alectinib microparticles were successfully formulated and spray-dried, resulting in a dry powder suitable for inhalation. This formulation enables the convenient pulmonary delivery of the ALK inhibitor, offering a promising approach for targeted delivery, which maximizes local drug concentration at the target site and reduces systemic exposure and associated side effects.
Keywords
Inhalable PLGA microparticles, Targeted Therapy, ALK-positive, NSCLC, Alectinib
