3 research outputs found
Biodegradable PEG-poly(ω-pentadecalactone- co - p -dioxanone) nanoparticles for enhanced and sustained drug delivery to treat brain tumors
Intracranial delivery of therapeutic agents is limited by penetration beyond the blood-brain barrier (BBB)
and rapid metabolism of the drugs that are delivered. Convection-enhanced delivery (CED) of drugloaded
nanoparticles (NPs) provides for local administration, control of distribution, and sustained
drug release. While some investigators have shown that repeated CED procedures are possible, longer
periods of sustained release could eliminate the need for repeated infusions, which would enhance
safety and translatability of the approach. Here, we demonstrate that nanoparticles formed from
poly(ethylene glycol)-poly(u-pentadecalactone-co-p-dioxanone) block copolymers [PEG-poly(PDL-co-
DO)] are highly efficient nanocarriers that provide long-term release: small nanoparticles (less than
100 nm in diameter) continuously released a radiosensitizer (VE822) over a period of several weeks
in vitro, provided widespread intracranial drug distribution during CED, and yielded significant drug
retention within the brain for over 1 week. One advantage of PEG-poly(PDL-co-DO) nanoparticles is that
hydrophobicity can be tuned by adjusting the ratio of hydrophobic PDL to hydrophilic DO monomers,
thus making it possible to achieve a wide range of drug release rates and drug distribution profiles. When
administered by CED to rats with intracranial RG2 tumors, and combined with a 5-day course of fractionated
radiation therapy, VE822-loaded PEG-poly(PDL-co-DO) NPs significantly prolonged survival
when compared to free VE822. Thus, PEG-poly(PDL-co-DO) NPs represent a new type of versatile
nanocarrier system with potential for sustained intracranial delivery of therapeutic agents to treat brain
tumors