Polyelectrolyte Multilayer Nanoshells With Hydrophobic Nanodomains for Delivery of Paclitaxel

Abstract

Efficient and effective delivery of poorly water-soluble drug molecules, which constitute a large part of commercially available drugs, is a major challenge in the field of drug delivery. Several drugs including paclitaxel (PTX) which are used for cancer treatment are hydrophobic, exhibit poor aqueous solubility and need to be delivered using an appropriate carrier. In the present work, we engineered Taxol-loaded polyelectrolyte films and microcapsules by pre-complexing PTX with chemically modified derivative of hyaluronic acid (alkylamino hydrazide) containing hydrophobic nanocavities, and subsequent assembly with either poly(L-lysine) (PLL) or quaternized chitosan (QCHI) as polycations. The PTX loading capacity of the films was found to be dependent on number of layers in the films as well as on the initial concentration of PTX precomplexed to hydrophobic HA, with a loading capacity up to 5000-fold the initial PTX concentration. The films were stable in physiological medium and were degraded in the presence of hyaluronidase. The PTX-loaded microcapsules were found to decrease the viability and proliferation of MDA MB 231 breast cancer cells, while unloaded microcapsules did not impact cell viability. All together, our results highlight the potential of hyaluronan-based assemblies containing hydrophobic nanodomains for hydrophobic drug delivery.

Emerging methods for the fabrication of polymer capsules

“…Effective drug delivery vectors have several key requirements [240][241][242][243][244]: low toxicity and optional degradability; high loading capacity; triggered release mechanisms, such as pH-, enzyme-, or redox-triggered; low immunogenicity; and targeting groups to direct the vector to designated sites. Drug and therapeutic molecule loading can be achieved by several routes, including: co-assembly of polymer-drug conjugates [119,151,245]; drug post-loading by temporarily altering capsule permeability [246][247][248][249][250][251]; pre-loading of therapeutics to functional templates [176,[252][253][254][255][256][257]; or incorporation into specific domains of the capsule [142,258,259].…”

Advances in cellular and tissue engineering using layer‐by‐layer assembly

“…There is tremendous potential to combine this pH‐based targeting with drug‐releasing LbL film architectures to deliver a chemotherapeutic at a tumor site. In fact, it has been shown that HA derivatives containing hydrophobic nanodomains can be complexed with hydrophobic small molecules, including the chemotherapeutic paclitaxel, to allow for drug loading into an LbL film containing these modified HA molecules and polyelectrolytes, including PLL and quaternized chitosan . The release of paclitaxel from these films was shown to be hyaluronidase‐sensitive, an enzyme that is often upregulated in certain breast cancers .…”

“…In fact, it has been shown that HA derivatives containing hydrophobic nanodomains can be complexed with hydrophobic small molecules, including the chemotherapeutic paclitaxel, to allow for drug loading into an LbL film containing these modified HA molecules and polyelectrolytes, including PLL and quaternized chitosan . The release of paclitaxel from these films was shown to be hyaluronidase‐sensitive, an enzyme that is often upregulated in certain breast cancers . HA has also been used to capture paclitaxel‐loaded block copolymer micelle nanocarriers subsequently layered with polycations, leading to controlled release of paclitaxel and demonstrating reduced in vitro proliferation of human aortic smooth muscle cells …”

Spatio‐Temporal Control of LbL Films for Biomedical Applications: From 2D to 3D

“…Liver parenchymal cells have thus been successfully targeted by glycans-presenting LbL capsules, as these cells express receptors presenting lectins, proteins that recognize sugar complexes [101–103] . Tumor-targeted systems have also been developed, targeting either folate receptors [104] or CD44 glycoproteins [105,106] , as these receptors are overexpressed on many cancer cell membranes.…”