title: Ultrathin antibiotic walled microcapsules.
abstract: Ultrathin microcapsules comprised of anionic polyelectrolytes (PE) and a polycationic aminoglycoside (AmG) antibiotic drug were prepared by depositing PE/AmG multilayers on zinc oxide (ZnO) colloid particles using the layer-by-layer self-assembly technique and subsequently dissolving the ZnO templated cores. The polyelectrolytes, dextran sulfate sodium (DxS) and poly(styrenesulfonate) (PSS), were selected owing to their different backbone structure. An aminoglycoside, tobramycin sulfate (TbS), was used for studying DxS/TbS or PSS/TbS multilayer films. The multilayer growth on ZnO cores was characterized by alternating zeta potential values that were different for the DxS/TbS and PSS/TbS multilayers due to the PE chemistry and its interaction with Zn(2+) ions. Transmission and scanning electron microscopy provide evidence of PE/TbS multilayer coating on ZnO core particles. The slow acid-decomposition of the ZnO cores using weak organic acids and the presence of sufficient quantity of Zn(2+) in the dispersion were required to produce antibiotic multilayer capsules. There was no difference in the morphological characteristics of the two types of capsules; although, the yield for [PSS/TbS](5) capsules was significantly higher than for [DxS/TbS](5) capsules which was related to the physicochemical properties of DxS/TbS/Zn(2+) and PSS/TbS/Zn(2+) complexes forming the capsule wall. The TbS quantity in the multilayer films was determined using a quartz crystal microbalance and high performance liquid chromatography techniques which showed less TbS loading in both, capsules and multilayers on planar gold substrate, than the theoretical DxS:TbS or PSS:TbS stoichiometric ratio. The decomposition of the [PE/TbS](6) multilayers was fastest in physiological buffer followed by mannitol and water. The decomposition rate of the [PSS/TbS](6) multilayers was slower than [DxS/TbS](6) monolayers. The incomplete decomposition of DxS/TbS under saline conditions suggests the major role of hydrogen bonding for stability of DxS/TbS multilayers. A combination of hydrogen bonding and hydrophobic interaction between phenyl rings in PSS was responsible for PSS/TbS multilayer stability. In vivo studies in rabbits highlight the safety and sustained drug delivery potential of the PE/AmG microcapsules. The antibiotic walled ultrathin capsules presented here are suitable for sustained ophthalmic antibiotic delivery.
authors.affiliation: Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, D-14476 Golm, Germany. ajkhopade@sunpharma.com
authors.forename: Ajay J
authors.initials: AJ
authors.lastname: Khopade
authors.forename: N
authors.initials: N
authors.lastname: Arulsudar
authors.forename: Surekha A
authors.initials: SA
authors.lastname: Khopade
authors.forename: J
authors.initials: J
authors.lastname: Hartmann
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002214:Capsules / Q000737:chemistry; D016264:Dextran Sulfate / Q000737:chemistry; D015195:Drug Design; D005131:Eye Injuries / Q000139:chemically induced; D008567:Membranes, Artificial; D015394:Molecular Structure; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry; D011817:Rabbits; D013997:Time Factors; D015034:Zinc Oxide / Q000737:chemistry
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002214:Capsules; D008567:Membranes, Artificial; D011108:Polymers; D011137:Polystyrenes; C003321:polystyrene sulfonic acid; D016264:Dextran Sulfate; D015034:Zinc Oxide