Polyethylene Oxide Modified PolyPAmino Ester Nanoparticles

A representative biodegradable, hydrophobic poly(b-amino ester) (PBAE) with pHsensitive solubility properties was synthesized by conjugate addition of 4,4'-trimethylenedipiperidine with 1,4-butanediol diacrylate, developed in Professor Robert Langer's lab at Massachusetts Institute of Technology. The paclitaxel-loaded nanoparticles (150-200 nm) prepared from PBAE were modified with Pluronic® F-108 (poloxamer 407), a triblock copolymer of polyethylene oxide/polypropylene oxide/polyethylene oxide (PEO/PPO/PEO). The PPO segment of the triblock polymer attaches to the hydrophobic surface of the nanoparticles, and the hydrophilic PEO segment contributes to the stealth properties of the polymeric nanoparticles. The pH-sensitive nature of the particles prepared from PBAE has already been shown by in vitro release studies carried out in the presence of buffers of pH ranging from 5.0 to 7.4 and was found to rapidly degrade in a medium of pH less than 6.5. Therefore, these nanoparticles were expected to readily release their contents within the acidic tumor microenvironment and in the endosomes and lysosomes of the cells upon internal-ization. This was confirmed by the in vitro cellular uptake of the PEO-PBAE nanoparticles encapsulated with tritiated [3H]-paclitaxel by human breast adenocarcinoma cells (MDA-MB231).49,50

The biodistribution of these PEO-modified PBAE nanoparticles was carried out by encapsulating a lipophilic form of the radionuclide indium-111 (111indium oxine). Following tail vein injection in nude mice bearing a human ovarian xenograft, the radiolabeled PEO-modified PBAE nanoparticles were found to accumulate in the highly perfused organs such as the liver, spleen, and lungs with greater entrapment in the microvasculature of the lungs during the initial time points. The increasing concentrations in the kidney also indicate that the nanoparticles, once internalized, were disintegrated and eliminated through the kidney. The plasma half-life of the unmodified nanoparticles was reported to be one to ten minutes. By virtue of surface modification with PEO, the PBAE nanoparticles were shown to have improved circulation times, resulting in a mean residence time in the systemic circulation of 21 h. The paclitaxel-encapsulated PEO-PBAE nanocarriers were found to deliver the drug efficiently to solid tumors, resulting in a 5.2-fold and 23-fold higher concentration of the drug at one hour and five hours post-administration relative to the solution form of the drug.40 From the tumor accumulation of the paclitaxel-loaded (3H-labeled) nanoparticles, it is evident that the pH-sensitive PEO-PBAE nanoparticle formulations can deliver significantly higher concentrations of the drug into the tumor than the solution form.

Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook

Post a comment