Biodegradable and biocompatible polymeric nanoparticles
(NPs) stand
out as a key tool for improving drug bioavailability, reducing the
inherent toxicity, and targeting the intended site. Most importantly,
the ease of polymer synthesis and its derivatization to add functional
properties makes them potentially ideal to fulfill the requirements
for intended therapeutic applications. Among many polymers, US FDA-approved
poly(l-lactic-co-glycolic) acid (PLGA) is
a widely used biocompatible and biodegradable co-polymer in drug delivery
and in implantable biomaterials. While many studies have been conducted
using PLGA NPs as a drug delivery system, less attention has been
given to understanding the effect of NP weight on cellular behaviors
such as uptake. Here we discuss the synthesis of PLGA NPs with varying
NP weights and their colloidal and biological properties. Following
nanoprecipitation, we have synthesized PLGA NP sizes ranging from
60 to 100 nm by varying the initial PLGA feed in the system. These
NPs 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 delivery
potential of these nanoparticles (NPs) was assessed using doxorubicin
(DOX) as a model drug, loaded into the NP core at a concentration
of 7.0 ± 0.5 wt % to study its therapeutic effects. The results
showed that both concentration and treatment time are crucial factors
for exhibiting therapeutic effects, as observed with DOX-NPs exhibiting
a higher potency at lower concentrations. The observations revealed
that DOX-NPs exhibited a higher cellular uptake of DOX compared to
the free-DOX treatment group. This will allow us to reduce the recommended
dose to achieve the desired effect, which otherwise required a large
dose when treated with free DOX. Considering the significance of PLGA-based
nanoparticle drug delivery systems, we anticipate that this study
will contribute to the establishment of design considerations and
guidelines for the therapeutic applications of nanoparticles.