A novel type of biocompatible hollow capsules that combine severable favorable features as a hydrophobic drug carrier, including host−guest complexation in the shell, the unique biological functions of hyaluronic acid (HA), and transport properties of the multilayer shell, was designed and prepared. These capsules were generated by layer-by-layer (LbL) deposition of HA modified with β-cyclodextrin (CD) molecules and poly(L-lysine) (PLL) on calcium carbonate particles. Simultaneously, paclitaxel (PTX) was loaded in the LbL wall via host−guest interaction. Under physiological conditions, the incorporated anticancer drug was slowly released, and the capsules remained stable. Because the PTX molecules are selectively complexed by CD in the shell, their release can be triggered by the addition of competitive cyclodextrin molecules in the external medium. By incubating the capsules with breast cancer cells (MDA-MB-231), it was found that the cells bound specifically to the capsules through the CD44 receptor of HA that is overexpressed on their surface. Finally, when breast cancer cells were incubated with the PTX-loaded capsules, their viability was found to strongly decrease. All together, these results highlight the potential for these HA−cyclodextrin-containing capsules in anticancer therapy.

A hyaluronic acid (HA)-based extracellular matrix (ECM) platform with independently tunable stiffness and density of cell-adhesive peptide (RGD, arginine-glycine-aspartic acid) that mimics key biochemical and mechanical features of brain matrix has been designed. We demonstrated here its utility in elucidating ECM regulation of neural progenitor cell behavior and neurite outgrowth. The analysis of neurite outgrowth in 3-D by two-photon microscopy showed several important results in the development of these hydrogels. First, the ability of neurites to extend deeply into these soft HA-based matrices even in the absence of cell-adhesive ligand further confirms the potential of HA hydrogels for central nervous system (CNS) regeneration. Second, the behavior of hippocampal neural progenitor cells differed markedly between the hydrogels with a storage modulus of 400 Pa and those with a modulus of 800 Pa. We observed an increased outgrowth and density of neurites in the softest hydrogels (G' = 400 Pa). Interestingly, cells seeded on the surface of the hydrogels functionalized with the RGD ligand experienced an optimum in neurite outgrowth as a function of ligand density. Surprinsingly, neurites preferentially progressed inside the gels in a vertical direction, suggesting that outgrowth is directed by the hydrogel structure. This work may provide design principles for the development of hydrogels to facilitate neuronal regeneration in the adult brain.