Therapeutic drug delivery is known to be influenced by interplay between various design parameters of delivery carriers which influence the drug uptake efficiency and subsequently the effectiveness of treatment. Amongst, the several design parameters such as size, shape and surface charge, particle shape is gaining attention as a crucial design parameter for development of robust and efficient delivery carriers. In this exploration, we investigated the influence of particle shape on injectability and therapeutic effectiveness of the delivery carriers using doxorubicin (DOX) conjugated polymeric microparticles. Results of injectability experiments demonstrated the influence of particle shape with anisotropic rod-shaped particles displaying increased injectability as against spherical particles. Impact of particle shape on therapeutic effectiveness was assessed against small cell lung cancer (SCLC) which was selected as a model disease. Results of cellular uptake studies revealed preferential uptake of rod-shaped particles than spherical particles in cancer cells. These results were further validated by in-vitro tumor simulation studies wherein rod-shaped particles displayed enhanced anti-tumorigenic activity along with distortion of tumor integrity against spheres. Furthermore, the impact of particle size was also assessed on cardiotoxicity, an adverse effect of DOX which limits its therapeutic use. Results illustrated that the high aspect ratio particles displayed diminished cardiotoxicity activity. These results provide valuable insights about influence of particle shape for designing efficient therapeutics.
Keywords: Anisotropic; Aspect ratio; Cardiotoxicity; Cellular uptake; Injectability; Lung cancer; Particle shape.
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