2 research outputs found
Biocompatible and Photostable Photoacoustic Contrast Agents as Nanoparticles Based on Bodipy Scaffold and Polylactide Polymers: Synthesis, Formulation, and <i>In Vivo</i> Evaluation
We have designed a new Bodipy scaffold for efficient in
vivo photoacoustic (PA) imaging of nanoparticles commonly
used as drug nanovectors. The new dye has an optimized absorption
band in the near-infrared window in biological tissue and a low fluorescence
quantum yield that leads to a good photoacoustic generation efficiency.
After Bodipy-initiated ring-opening polymerization of lactide, the
polylactide–Bodipy was formulated into PEGylated nanoparticles
(NPs) by mixing with PLA–PEG at different concentrations. Formulated
NPs around 100 nm exhibit excellent PA properties: an absorption band
at 760 nm and a molar absorption coefficient in between that of molecular
PA absorbers and gold NPs. Highly improved photostability compared
to cyanine-labeled PLA NPs as well as innocuity in cultured macrophages
were demonstrated. After intravenous injection in healthy animals,
NPs were easily detected using a commercial PA imaging system and
spectral unmixing, opening the way to their use as theranostic agents
A Polymer Prodrug Strategy to Switch from Intravenous to Subcutaneous Cancer Therapy for Irritant/Vesicant Drugs
Chemotherapy is almost exclusively administered via the
intravenous
(IV) route, which has serious limitations (e.g., patient discomfort,
long hospital stays, need for trained staff, high cost, catheter failures,
infections). Therefore, the development of effective and less costly
chemotherapy that is more comfortable for the patient would revolutionize
cancer therapy. While subcutaneous (SC) administration has the potential
to meet these criteria, it is extremely restrictive as it cannot be
applied to most anticancer drugs, such as irritant or vesicant ones,
for local toxicity reasons. Herein, we report a facile, general, and
scalable approach for the SC administration of anticancer drugs through
the design of well-defined hydrophilic polymer prodrugs. This was
applied to the anticancer drug paclitaxel (Ptx) as a worst-case scenario
due to its high hydrophobicity and vesicant properties (two factors
promoting necrosis at the injection site). After a preliminary screening
of well-established polymers used in nanomedicine, polyacrylamide
(PAAm) was chosen as a hydrophilic polymer owing to its greater physicochemical,
pharmacokinetic, and tumor accumulation properties. A small library
of Ptx-based polymer prodrugs was designed by adjusting the nature
of the linker (ester, diglycolate, and carbonate) and then evaluated
in terms of rheological/viscosity properties in aqueous solutions,
drug release kinetics in PBS and in murine plasma, cytotoxicity on
two different cancer cell lines, acute local and systemic toxicity,
pharmacokinetics and biodistribution, and finally their anticancer
efficacy. We demonstrated that Ptx-PAAm polymer prodrugs could be
safely injected subcutaneously without inducing local toxicity while
outperforming Taxol, the commercial formulation of Ptx, thus opening
the door to the safe transposition from IV to SC chemotherapy