Biomedical Engineering Reference
In-Depth Information
naturally occurring polysaccharide approved by the FDA for various
uses, including in food products and wound dressings. It is readily
cross-linked by divalent cations such as calcium to form a solid matrix
without the use of organic solvents [57, 58]. Scaffolds made from
alginate readily decompose in the presence of sodium ions which
are naturally occurring within the body and thus serve as a trigger
to release entrapped therapeutics slowly over time [59]. Alginate
has been previously used in gene delivery either as microspheres
[57], poly-ionic complexes [60-62], or hydrogel [58]. Wu
. were
the first to report the use of alignate in the form of PLAS for siRNA
delivery in the vaginal tract [52].
et al
Alginate + PEGylated
liposome mixture
Freeze gradually to -80°C
Freeze gradually to -80�C
Lyophilize
Add CaCl
2
solution (RT)
Add CaCl2 solution (RT)
Air dry at RT
Figure 9.3
Flow chart of the fabrication of PLAS via freeze-dried method.
PLAS was generated by mixing PEG lipoplexes in a 2% solution
of alginate in isotonic dextrose and freezing the solution slowly
to -80°C before freeze drying (detailed methods are described in
[52]). The dried matrix was cross-linked by immersing the matrix
in a 5% calcium chloride solution for 3 min before drying overnight.
Entrapment efficiencies of lipoplexes were ~50%. Using a mold in the
freeze-drying step allows one to achieve any shape PLAS one desires.
In the case of the vaginal tract we used 10 mm square sheets that
were rolled into cigar-shaped cylinders that made insertion simple
and easy. We found that upon exposure to fluids with vaginal pH and
sodium characteristics, ~50% of the siRNAs was released within
1 h, the limiting step appearing to be the sodium-calcium exchange.
Increasing sodium concentrations resulted in increased siRNA
release. The particles retained their particle size and polydispersity.
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