Nanocrystalline hydroxyapatite and zinc-doped hydroxyapatite as carrier material for controlled delivery of ciprofloxacin

In bone disorders infections are common. The concentration of majority of antibiotics is very low in the bone tissue. A high local dose can be obtained from the ciprofloxacin-loaded hydroxyapatite nanoparticles. The present study is aimed at developing the use of hydroxyapatite and zinc-doped hydroxyapatite nanoparticles as a carrier for ciprofloxacin drug delivery system. The ciprofloxacin-loaded hydroxyapatite and zinc-doped hydroxyapatite have a good antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus. Hydroxyapatite and zinc-doped hydroxyapatite were prepared and characterized using X-ray diffraction, Transmission electron microscopy and inductively coupled plasma optical emission spectrometry. They were loaded with ciprofloxacin using optimized drug loading parameters. Drug loading, in vitro drug release and antimicrobial activity were analyzed. The influence of zinc on the controlled release of ciprofloxacin was analyzed. The results show that the presence of zinc increases the drug release percentage and that the drug was released in a controlled manner

Controlled-release nanoencapsulating microcapsules to combat inflammatory diseases

Jong-Suep Baek,1 Eng Wan Yeo,1 Yin Hao Lee,2 Nguan Soon Tan,2 Say Chye Joachim Loo1,3 1School of Materials Science and Engineering, Nanyang Technological University, Singapore; 2School of Biological Sciences, Nanyang Technological University, Singapore; 3Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore Abstract: The World Health Organization (WHO) has reported that globally 235 million people suffer from chronic and other inflammatory diseases. The short half-lives of nonsteroidal anti-inflammatory drugs (NSAIDs) and their notoriety in causing gastrointestinal discomforts, warrants these drugs to be released in a controlled and sustained manner. Although polymeric particles have been widely used for drug delivery, there are few reports that showcase their ability in encapsulating and sustaining the release of NSAIDs. In this paper, polymeric nanoencapsulating microcapsules loaded with NSAIDs were fabricated using solid/water/oil/water emulsion solvent evaporation method. Two NSAIDs, ibuprofen and naproxen, were first pre-loaded into nanoparticles and then encapsulated into a larger hollow microcapsule that contained the third NSAID, celecoxib. A high encapsulation efficiency (%) of these NSAIDs was achieved and a sustained release (up to 30 days) of these drugs in phosphate-buffered saline was observed. Then, a gastrointestinal drug – cimetidine (CIM) – was co-loaded with the NSAIDs. This floating delivery system exhibited excellent buoyancy (~88% up to 24 h) in simulated gastric fluid. It also allowed a sequential release of the drugs, whereby an immediate release of CIM followed by NSAIDs was observed. Drug release of the NSAIDs observed Fickian diffusion mechanism, whereas CIM observed non-Fickian diffusion. Therefore, this delivery system is a promising platform to control the delivery of NSAIDs to combat inflammatory diseases, thereby protecting against possible gastrointestinal side effects that may arise from the overuse of NSAIDs. Keywords: NSAIDs, multi-drug encapsulation, sequential release, floating oral drug delivery, injectable system, oral delivery systems, diffusion, emulsion, sustained releas

A programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to Gram-positive and Gram-negative bacterial biofilms

© 2018 The Royal Society of Chemistry. Bacteria enmeshed in an extracellular matrix, biofilms, exhibit enhanced antibiotic tolerance. Coupled with the rapid emergence of multidrug-resistant strains, the current cohorts of antibiotics are becoming ineffective. Alternative antimicrobial approaches are therefore urgently needed to overcome recalcitrant biofilm infections. Here, we propose the use of a non-toxic lipid-polymer hybrid nanoparticle (LPN) system composed of a solid polymer core (i.e. PLGA; poly lactic-co-glycolic acid) and a cationic lipid shell (i.e. DOTAP) for localized, sustained release of antimicrobial agents to bacterial biofilms. LPNs were synthesized through a simple, robust self-assembly approach. LPNs of uniform particle size (i.e. 100-130 nm), efficiently encapsulated (up to 95%) bioimaging molecules or antibiotics and provided controlled release of the latter. The cationic lipid coating enabled the LPN to anchor onto surfaces of a diverse range of Gram-positive and Gram-negative bacterial pathogens, either in the planktonic or biofilm form. Consistently, the LPN formulations reduced more than 95% of biofilm activity at concentrations that were 8 to 32-fold lower than free antibiotics. These data clearly indicate that these novel formulations could be a useful strategy to enhance the efficacy of antimicrobials against planktonic cells and biofilms of diverse species