PLA micro- and nano-particles have been proposed for improving
oral bioavailability of poorly water-soluble drugs. Nano-particles are
thought to be absorbed fromthe gastrointestinal tract after oral administration
[2,82]. Poorly water-soluble drugs are difficult to make into
suitable dosage forms with adequate oral bioavailability [16]. Particles
loaded with a poorly soluble drug can significantly increase the drug
dissolution rate. The intestine has a special mechanism to absorb particles
of certain sizes. The 100 nmparticles showed a significantly higher
uptake than larger particles [83,84]. Although gene therapy has been extensively
studied for treating genetic diseases and acquired diseases
[85], the safety and efficiency of gene delivery have not been examined
in depth. PLA-based micro- and nano-particles have shown particular
promise in improving protection from plasma enzymes, alternative
routes of administration (e.g., nasal, oral, pulmonary, and mucosal),
and prolonged gene delivery efficacy [86–89]. Cationic PEG–PLA nanoparticles
are one of themajor delivery systems for the small interference
RNA (siRNA) system. Systemic delivery of small interfering polo-like
kinase 1 (siPlk1) by PEG–PLA nano-particles significantly suppressed
tumor growth in an MDA-MB-435 s (cancer cells) murine xenograft
model [90]. siRNA encapsulated in PEG–PLA nano-particles were
shown to have successfully entered the cells and resulted in remarkable
gene-specific knockdown in the adult zebrafish heart [91]. PLA-based
nano-particles containing polyethyleneimine (PEI) on their surfaces
were used for incorporating genes. PEO–PLA–PEI was also used for codelivery
of supercoiled minicircle (mc) DNA vectors and Dox. These
nano carrier systems have the advantage of non-fouling oxazolines to
confer biological stability, of PLA to provide hydrophobicity for Dox encapsulation
and of bioreductive PEI to provide gene complexation. The
dual delivery of mcDNA-Dox to B16F10 (Mus musculus skin melanoma
cell line; ATCC® CRL-6475™)-Luciferase tumor-bearing mice resulted
in significantly reduced tumor size and cancer cells' viability [92]. Recently,
dual- or multi-drug delivery systems have shown great potential
in the drug delivery field for cancer and gene therapy.