Drug Delivery Systems That Eradicate and/or Prevent Biofilm Formation - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 404

lowering systemic drug toxicity, improving treatment absorption rates, and provid-
ing protection for pharmaceuticals against biochemical degradation (Sanli
et al. 2008 ).

3.1 Poly( DL -lactide-co-glycolide) Nanocapsule-Based Drug
Delivery Systems

PLGA is a clinically approved (FDA), biodegradable, and biocompatible polymer
considered safe for controlled release formulations (Lu et al. 2009 ). PLGA is poly-
ester consisting of one or more different hydroxy acid monomers, D -lactic, L -lactic,
and/or glycolic acids. In general, the polymer, can be made to be highly crystalline
[e.g., poly( L -lactic acid)], or completely amorphous [e.g., poly( DL -lactic-co-glycolic
acid)], can be processed into most any shape and size (down to 200 nm), and can

encapsulate molecules of virtually any size. PLGA is one of the most effectively used
polymers for the development of a drug delivery system because it undergoes
hydrolysis in the body to produce the biodegradable metabolite monomers, lactic
acid and glycolic acid, which are assimilated by the body, resulting in minimal
systemic toxicity (Wu 1995 ). Many approaches have been proposed for the prepara-
tion of PLGA particles. The emulsification-evaporation method (Sahoo et al. 2004 ),
the spontaneous emulsification-solvent diffusion method (SESD) (Bilati et al. 2005 ),
the nanoprecipitation method (Govender et al. 1999 ;Riveraetal. 2004 ), and the
spray-drying method (Takashima et al. 2007 ; Cheng et al. 2008 ) are all widely used in
preparing PLGA nano/microparticles of various size.
PLGA polymers have been used to trap several antibiotics in nanoparticle
formulations, demonstrating improved delivery and antibiotic efficacy (Pillai
et al. 2008 ; Mohammadi et al. 2010 ; Kashi et al. 2012 ). Notably, Cheow
et al. ( 2010 ) reported the preparation of levofloxacin loaded poly( DL -lactide-co-
glycolide) (PLGA) and poly(caprolactone) (PLC) nanoparticles and showed that, to
be effective against E. coli biofilm cells, the formulation required a biphasic
extended release profile. This release profile consisted of an initial fast release,
providing high antibiotic concentrations for biofilm eradication, followed by slower
extended release that minimized biofilm growth and infection exacerbation.
Katherine et al. ( 2012 ) verified that cinnamaldehyde (CA) and carvacrol (CARV)
in solution significantly impaired bacterial growth, and therefore biofilm formation,
by E. coli, P. aeruginosa , and S. aureus at low concentrations. A PLGA formulation
of gentamicin also demonstrated improved antimicrobial effects on peritoneal
infection caused by P. aeruginosa biofilms in vivo (Sharif et al. 2012a , b ).