Page 309 - Biodegradable Polyesters

11.3 Uniquely Encapsulated Drug/Biopolymer Nanofiber Systems for Drug Delivery 287

nearly constant and linear release of the model drug Levetiracetam from PLGA
emulsion-coaxial electrospun fibers is observed over 20 days. This device is aimed
to be implanted into the brain for treatment of epilepsy, which is an example of the
new capabilities and promising potential that emulsion-coaxial electrospinning
can provide toward the development of future drug carriers [71].
Emulsion electrospinning was also used to prepare core–sheath structured
fibers with core loading of hydroxycamptothecin (HCPT), whose antitumor
activities were evaluated both in vitro on cancer cell lines and in vivo on tumor-
bearing mice via intratumoral implantation [72]. Compared with the previous
investigations on blend electrospun fibers, the addition of 2-hydroxypropyl-β-
cyclodextrin (HPCD) and the preferential formation of HCPT/HPCD inclusion
complexes resulted in higher degradation rate of emulsion electrospun fibers and
significantly faster HCPT release rate. In vitro cytotoxicity tests on HCPT-loaded
electrospun fibers indicated over 20 times higher inhibitory activity against
HepG2 cells than free HCPT during 72 h incubation. Hepatoma H22 cells were
subcutaneously injected into Kunming mice to form solid tumors for in vivo tests
on the antitumor efficacy. On the basis of the tumor volume, survival rate, and
body weight changes, HCPT-loaded fibers indicated superior in vivo antitumor
activities and less side effects than free HCPT. The histopathological staining
and immunohistochemical examinations of caspase-3 expression indicated more
necrosis and apoptosis induced by HCPT-loaded fibers as shown in Figure 11.7.
The above results demonstrate the potential use of emulsion electrospun fibers
as drug carriers for local treatment of solid tumors.
Biodegradable microparticulate systems have been used widely for controlled
release of protein drugs for days and months. The important factors in developing
biodegradable microparticles for protein drug delivery are protein release profile
(including burst release, duration of release, and extent of release), microparticle
size, protein loading, encapsulation efficiency, and bioactivity of the released
protein [73]. Yang et al. assessed the potential use of emulsion electrospinning
to prepare core–shell structured ultrafine (poly[D,L-lactic acid]) (PDLLA) fibers
as carriers for therapeutic proteins. In vitro release study indicated that with
the use of lower volume ratio of aqueous to organic phase in the emulsion can
reduce the initial protein burst and improve the ability of the device to provide
sustained therapeutic action. Size exclusion chromatography analysis indicated
that ultrasonication caused some aggregation or intermolecular association of
BSA molecules while core–shell structured electrospun fibers could protect the
structural integrity of encapsulated BSA during incubation in a medium. FTIR
analyses showed that ultrasonication caused a more significant effect on the
secondary structure of BSA molecules than the electrospinning process. These
data suggest that emulsion electrospinning can provide a useful core–sheath
structure, which may serve as a promising scaffold for sustainable, controllable,
and effective release of bioactive proteins in tissue engineering and other appli-
cations. Yang et al. also revealed that plasmid DNA (pDNA) can be encapsulated
into core–sheath fibers using an emulsion electrospinning method [74]. They
found that the effective release lifetime of pDNA polyplexes can be controlled