A recently patented
one-step
in situ
cross-linked
alginate microencapsulation (CLAM) by spray-drying (i.e., the UC Davis
CLAMs technology) can overcome the high cost of scale-up that limits
commercial applications. While increasing calcium loading in the CLAMs
process can increase the extent of cross-linking and improve retention
and protection of the encapsulated cargo, the potential for residual
undissolved calcium salt crystals in the final product can be a concern
for some applications. Here, we demonstrate an alternate one-step
spray-dry CLAMs process using pH-responsive chelation of calcium.
The “Chelate CLAMs” process is an improvement over the
patented process that controls ion availability based on pH-responsive
solubility of the calcium salt. Hyaluronic acid was encapsulated in
CLAMs to minimize swelling and release in aqueous formulations. CLAMs
with 61% (d.b.) hyaluronic acid (HA-CLAMs) demonstrated restricted
plumping, limited water absorption capacity, and reduced leaching,
retaining up to 49% hyaluronic acid after 2 h in water. Alternatively,
“Chelate HA-CLAMs” formed by the improved process exhibited
nearly full retention of hyaluronic acid over 2 h in water and remained
visibly insoluble after 1 year of storage in water at 4 °C. Successful
hyaluronic acid retention in CLAMs is likely due in part to its ability
to cross-link with calcium.