Effect of Nanoparticle Weight on the Cellular Uptake and Drug Delivery Potential of PLGA Nanoparticles

Biodegradable and biocompatible polymeric nanoparticles(NPs) standout as a key tool for improving drug bioavailability, reducing theinherent toxicity, and targeting the intended site. Most importantly,the ease of polymer synthesis and its derivatization to add functionalproperties makes them potentially ideal to fulfill the requirementsfor intended therapeutic applications. Among many polymers, US FDA-approvedpoly(l-lactic-co-glycolic) acid (PLGA) isa widely used biocompatible and biodegradable co-polymer in drug deliveryand in implantable biomaterials. While many studies have been conductedusing PLGA NPs as a drug delivery system, less attention has beengiven to understanding the effect of NP weight on cellular behaviorssuch as uptake. Here we discuss the synthesis of PLGA NPs with varyingNP weights and their colloidal and biological properties. Followingnanoprecipitation, we have synthesized PLGA NP sizes ranging from60 to 100 nm by varying the initial PLGA feed in the system. TheseNPs were found to be stable for a prolonged period in colloidal conditions.We further studied cellular uptake and found that these NPs are cytocompatible;however, they are differentially uptaken by cancer and immune cells,which are greatly influenced by NPs' weight. The drug deliverypotential of these nanoparticles (NPs) was assessed using doxorubicin(DOX) as a model drug, loaded into the NP core at a concentrationof 7.0 & PLUSMN; 0.5 wt % to study its therapeutic effects. The resultsshowed that both concentration and treatment time are crucial factorsfor exhibiting therapeutic effects, as observed with DOX-NPs exhibitinga higher potency at lower concentrations. The observations revealedthat DOX-NPs exhibited a higher cellular uptake of DOX compared tothe free-DOX treatment group. This will allow us to reduce the recommendeddose to achieve the desired effect, which otherwise required a largedose when treated with free DOX. Considering the significance of PLGA-basednanoparticle drug delivery systems, we anticipate that this studywill contribute to the establishment of design considerations andguidelines for the therapeutic applications of nanoparticles.