1 research outputs found
Click Biotinylation of PLGA Template for Biotin Receptor Oriented Delivery of Doxorubicin Hydrochloride in 4T1 Cell-Induced Breast Cancer
PLGA was functionalized with PEG
and biotin using click chemistry
to generate a biotin receptor targeted copolymer (biotinylated–PEG-PLGA)
which in turn was used to fabricate ultrafine nanoparticles (BPNP)
of doxorubicin hydrochloride (DOX) for effective delivery in 4T1 cell
induced breast cancer. However, adequate entrapment of a hydrophilic
bioactive like DOX in a hydrophobic polymer system made of PLGA is
not usually possible. We therefore modified a conventional W/O/W emulsion
method by utilizing NH<sub>4</sub>Cl in the external phase to constrain
DOX in dissolved polymer phase by suppressing DOX’s inherent
aqueous solubility as per common ion effect. This resulted in over
8-fold enhancement in entrapment efficiency of DOX inside BPNP, which
otherwise is highly susceptible to leakage due to its relatively high
aqueous solubility. TEM and DLS established BPNP to be sized below
100 nm, storage stability studies showed that BPNP were stable for
one month at 4 °C, and <i>in vitro</i> release suggested
significant control in drug release. Extensive <i>in vitro</i> and <i>in vivo</i> studies were conducted to propound
anticancer and antiproliferative activity of BPNP. Plasma and tissue
distribution study supplemented by pertinent <i>in vivo</i> fluorescence imaging mapped the exact fate of DOX contained inside
BPNP once it was administered intravenously. A comparative safety
profile via acute toxicity studies in mice was also generated to out
rightly establish usefulness of BPNP. Results suggest that BPNP
substantially enhance anticancer activity of DOX while simultaneously
mitigating its toxic potential due to altered spatial and temporal
presentation of drug and consequently deserve further allometric iteration