Extended Release Antibacterial Layer-by-Layer Films Incorporating Linear-Dendritic Block Copolymer Micelles

Abstract

The electrostatic layer-by-layer (LbL) assembly approach offers large potential in the area of drug delivery from thin films; however, because the processing technique is aqueous-based, there have been few strategies proposed to incorporate hydrophobic molecules into these films. Here we create an LbL film that is capable of incorporating hydrophobic drug at high loadings via encapsulation with lineardendritic block copolymer micelles and demonstrate for the first time release times of a hydrophobic antibacterial agent over a period of several weekssa significant improvement over reports of other micelleencapsulated thin films with release times of several minutes. The amphiphilic linear-dendritic block copolymer is composed of poly(propylene oxide) (PPO), which forms the hydrophobic core creating the compartment for hydrophobic drug encapsulation, and poly(amidoamine) (PAMAM), which forms the outer corona of the micelle. The PAMAM is polycationic, enabling LbL deposition with negatively charged poly(acrylic acid) (PAA). The stable PPO-PAMAM micelles incorporated into the LbL films encapsulated a hydrophobic bactericide, triclosan, which have loading capacities as high as 80-90%. Film thickness and UV-vis measurements confirm the formation of the LbL film and incorporation of triclosan into the film. Fluorescence measurements of PPO-PAMAM/PAA films with pyrene indicated the presence of hydrophobic domains in the film. GISAXS revealed regular spacing of approximately 10.5 nm in the direction parallel to the film substrate, which is approximately the same size as the PPO-PAMAM micelles in aqueous solution. Volume fraction measurements based on elemental analysis and TGA confirm the GISAXS data. An in vitro release study revealed long release times of triclosan on the order of weeks, and a Kirby Bauer test was performed on Staphylococcus aureus, demonstrating that the drug released was still active to inhibit the growth of bacteria.

Micelles‐Encapsulated Microcapsules for Sequential Loading of Hydrophobic and Water‐Soluble Drugs

“…[20][21][22][23][24][25][26][27] Hydrophobic dyes or drugs are loaded and controlled released from the planar multilayers. [22,24,25] The micelles in the capsule wall are designed as nano-reservoirs for the loading of hydrophobic drugs. [27] However, in order to achieve high capacity, the number of assembled layers should be high and this process is really time consuming.…”

Sustained delivery of siRNAs targeting viral infection by cell-degradable multilayered polyelectrolyte films

“…Self-assembled multilayer architectures can be built by using macromolecules or materials as different as polyelectrolytes, proteins, inorganic complexes, clay platelets, or colloidal particles, all adsorbed from aqueous solutions or suspensions. Although complex multilayered architectures were shown to deliver a variety of molecules including drugs (4)(5)(6)(7)(8) and DNA (9)(10)(11)(12), it is unknown whether this technique is feasible for the sustained delivery of siRNAs.…”

Preparation of Glycy-l-Tyrosine intercalated layered double hydroxide film and its in vitro release behavior

“…It can also circumvent the relatively short residence time of oral gels on the mucosa, which is easily washed away and removed by saliva [24]. Many studies on polymer films as drug carrier have been reported in recent years [25,26], but the side effects of organic matrixes cannot be neglected. In this work, inorganic film of GlyTyr-LDH with good biocompatibility was prepared, and its application as a novel release formulation for drug was investigated.…”