(313a) Novel Degradable Ultrasmall Nanoparticles and Their Application in Drug Delivery

Poly(lactic
acid) (PLA) nanoparticles are considered effective devices for drug delivery
and targeting, mainly because of their degradable/biocompatible nature of the
polymer along with the suitable particle size. The four major parameters
assessing the quality of polymer particles for drug delivery applications are:
particle size, encapsulation efficiency, surface charge, and release behavior[1]. There are lots of methods to prepare PLA particles of
colloidal size, such as nanoprecipitation, emulsion-based methods, salting-out
methods, spray drying, and so on[2]. However, the minimum particle size
produced through anyone of the above techniques is around 100 nm.

The aim of this work is to assess a new approach to the
synthesis of PLA particles with smaller size. Through ring-opening
polymerization of L,L-Lactide using Sn(Oct)₂ as catalyst and
suitable co-catalysts, poly(lactic acid) chains are grown and functionalized.
Starting from these functionalized oligomers and applying conventional emulsion
polymerization process, very small PLA-based, fully degradable nanoparticles
with size as small as 15 nm are synthesized. Meanwhile, extremely narrow
particle distributions have been also obtained.

The degradation study has been carried out using different
particles in terms of size and PLA chain length as well. The rates of
degradation and release of lactic acid and its oligomers from the nanoparticles
have been measured by high performance liquid chromatography (HPLC)[4]. The
complete degradation kinetics of the PLA-block of the polymer chains has been
studied. Moreover, a relation between the time of complete degradation
(particle disappearance) and the corresponding polymer molecular weight has
been determined. Finally, the biocompatibility of these particles has been
proved by in vitro tests. The nanoparticles stabilized by TWEEN80 have
been incubated with U266
myeloma cell line at 37 °C. The
time-increasing viable cell counts and the high viability of the cells at the
end of the incubation prove that these particles are non-toxic.

Such
ultra-small nanoparticles are very promising for special drug delivery
applications. In particular they can be used to enhance the cellular uptake and
to increase the membrane passage, especially the blood brain barrier (BBB).
Similar studies are currently on going in collaboration with the Institute for
Pharmacological Research Mario Negri (Milano, Italy).

[1] Hans, M.L.,
Lowman, A.M., Curr.
Opin. Solid State Mater. Sci., 2002, 6, 319-327.

[2] Lassalle,
V., Ferreira, M., Macromol. Biosci. 2007, 7, 767-783.

[3] Pending
patent.

[4] Codari, F., Moscatelli,
D., Storti, G., Morbidelli, M., Maromol. Mat. Eng, 2010, 1,
58.