- Nanoparticles of Poly(Lactide)/Vitamin E TPGS Copolymer for Cancer Chemotherapy: Synthesis, Formulation, Characterization and in vitro Drug Release

Nanoparticle formulation of anticancer drugs has become an important research

area in cancer nanotechnology, which can provide a way of sustained, controlled

and targeted drug delivery to improve the therapeutic effects and reduce the side

effects of the formulated drugs. Such drug delivery systems are usually restricted

by biocompatibility of the polymeric matrix material and the surfactant used

in the formulation process. Poly (lactide) (PLA), poly (d,l-lactide-co-glycolide)

(PLGA), and poly (caprolactone) (PCL) are FDA-approved biodegradable poly-

mers, which are used most often in the literature of drug delivery. These

polymers were originally synthesized to be used as surgical sutures, which thus

have disadvantages to be used for drug formulation such as too high hydro-

phobicity and too slow degradation. Novel biodegradable polymers/copolymers

with desired hydrophobic/hydrophilic balance and desired degradation rate are

thus needed. In the literature, PLGA nanoparticles were usually prepared by

using chemical emulsifiers such as poly (vinyl achohol) (PVA), which has been

found of disadvantages including low emulsification efficiency, side effects and

difficulties to wash away in the formulation process. Instead, d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or simply, TPGS) has high

emulsification efficiency (67 times higher than PVA). It can also greatly improve

the drug encapsulation efficiency (up to 100% EE achieved) and enhance

cellular uptake of nanoparticles and thus increase the cancer cell mortality

[1-5]. TPGS is a water-soluble derivative of natural vitamin E. Its hydrophile-

lipophile balance is ∼13. The chemical structure of TPGS is similar to other amphiphiles comprising lipophilic alkyl tail and hydrophilic polar head portion.

Its bulky structure and large surface area characteristics make it an excellent

emulsifier. Moreover, it has been found that co-administration of vitamin E

TPGS could enhance cytotoxicity, inhibit P-glycoprotein mediated multi-drug

resistance, and increase the oral bioavailability of anticancer drugs [6-8]. This

triggered us to take such advantages of TPGS to synthesize PLA-TPGS copolymers

for nanoparticle formulation of anticancer drugs, which can be expected to

have self-emulsification effects (no emulsifiers are needed for the nanoparticles

formulation) and achieve high drug encapsulation efficiency and desired drug

release profiles.