B. Gander et al., Polymers as a platform for drug delivery: Reviewing our current portfolio on poly(lactide-co-glycolide) (PLGA) microspheres, CHIMIA, 55(3), 2001, pp. 212-217
The chemical conjugation or the physical embodiment of therapeutic agents i
n polymers offers great potential to improve the efficacy and safety of the
rapies and create novel therapeutic opportunities. This has led to numerous
concepts regarding the formulation, the delivery and the targeting of ther
apeutics. Our current research portfolio in this field includes several pro
jects. In all of them poly(lactide-co-glycolide), PLGA, varying in molecula
r weight and end-group modification, is used as a delivery platform. In thi
s review we will firstly outline our concept of single-injection vaccines.
Instead of the application of repeated booster doses, such vaccines are des
igned to deliver the antigen in a pulsed or sustained fashion, in such a wa
y that protective humoral and cellular immunity can be achieved after a sin
gle injection. In the second polymer-based project we aim at the administra
tion of insulin-like growth factor I (IGF-I), which bears great potential i
n tissue engineering, e.g. to enhance bone healing. Here we summarize on a
PLGA microsphere system for the localized and controlled delivery of IGF-I
in order to close bone defects after fracture, pathology or surgery. In a t
hird project we use this polymeric platform for the design of antigen-encod
ing DNA vaccines designed to preferentially target the most potent antigen
presenting cells, i.e. the dendritic cells. Two prime objectives are curren
tly being studied, i) enhancement of phagocytosis of DNA-loaded PLGA micros
pheres by human-derived dendritic cells, and ii) release of intact plasmid
DNA and concomitant transfection of dendritic cells once the PLGA microsphe
res were successfully phagocytosed.