Abstract
This study demonstrates the possibility of developing a rapidly degradable chitosan-based multilayer film for controlled drug release. The chitosan (CHI)-based multilayer nanofilms were prepared with three different types of anions, hyaluronic acid (HA), alginic acid (ALG) and tannic acid (TA). Taking advantage of the Layer-by-Layer (LBL) assembly, each multilayer film has different morphology, porosity and thickness depending on their ionic density, molecular structure and the polymer functionality of the building blocks. We loaded drug models such as doxorubicin hydrochloride (DOX), fluorescein isothiocyanate (FITC) and ovalbumin (Ova) into multilayer films and analyzed the drug loading and release profiles in phosphate-buffered saline (PBS) buffer with the same osmolarity and temperature as the human body. Despite the rapid degradation of the multilayer film in a high pH and salt solution, the drug release profile can be controlled by increasing the functional group density, which results in interaction with the drug. In particular, the abundant carboxylate groups in the CHI/HA film increased the loading amount of DOX and decreased rapid drug release. The TA interaction with DOX via electrostatic interaction, hydrogen bonding and hydrophobic interaction showed a sustained drug release profile. These results serve as principles for fabricating a tailored multilayer film for drug delivery application.
Highlights
Development of smart drug delivery system (DDS) for the controlled drug loading and release manner has been considered essential to solving drug dosage, efficacy and safety issues
In the CHI/hyaluronic acid (HA) and CHI/ALG films, CHI chains acted as the diffusing species through the multilayer films, leading to improved accessibility of small molecules and exponential growth [27,28,30]
The CHI/HA film had a nanoporous structure with diffusion of the CHI chain during deposition; the CHI/ALG film had a dense structure with the deposition of highly ionized ALG chains and many carboxylate groups in multilayer film; and the CHI/tannic acid (TA) film had a macroporous structure with the deposition of rarely ionized CHI chains
Summary
Development of smart drug delivery system (DDS) for the controlled drug loading and release manner has been considered essential to solving drug dosage, efficacy and safety issues. The degradable properties of natural polymers and the high pH and salt level in vivo lead to a significant decrease in the stability of a multilayer film, resulting in an inadvertent drug release from the film. We studied the film structures, stability and functional group densities of chitosan-based multilayer films and their effect on drug loading and release profiles in environments with the same osmolarity and temperature as the human body. To fabricate a drug delivery platform with biocompatible and controlled drug release, we designed chitosan (CHI)-based multilayer films in which the CHI is combined separately with hyaluronic acid (HA), alginic acid (ALG) and tannic acid (TA). In the case of the CHI/ALG multilayer film, it has a dense structure and abundant carboxyl groups. All combinations released the drug rapidly within 30 min, with the film degradation
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