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In the United States, long standing deep infections of joint arthroplasty, such as total knee and total hip replacements, are treated with two-stage exchange. This requires the removal of the prior implant, placement of an antibiotic eluting spacer block made of polymethylmethacrylate (PMMA), followed by re-implantation of a new implant after treatment with intravenous antibiotics for six to eight weeks. Unfortunately, the use of PMMA as a spacer material has limitations in terms of mechanical and drug-eluting properties. PMMA is brittle and elutes most of the antibiotics within the first few days. Furthermore, the polymerization reaction for PMMA is highly exothermic, thereby limiting the use to heat-stable antibiotics. We hypothesize that the use of a 3D printed polymeric liner made of polylactic acid (PLA) would overcome the limitations of PMMA because it is a stronger and a less brittle material than PMMA. Furthermore, the liner can also act as a controlled drug delivery vehicle by using built in reservoirs and a network of micro-channels as well as by incorporating antibiotics directly into the polymer during manufacturing stage. Finally, the liner can be 3D printed according to the anatomy of the patient and thereby has the potential to transform the manner in which periprosthetic joint infections are currently treated., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Stent insertion and chemical agents of ethylene diamine tetraacetic acid and sodium cholate for dissolving common bile duct stone diseases through extra biliary tract infusion have been believed a relatively effective therapeutics for the clinical symptom. Core-shell nanofibers produced by co-axial electrospinning to deliver chemical drugs, biomacromolecules, genes and even cells have been reported for various advanced drug delivery system and tissue engineering applications. In the present study, poly (lactide-co-ɛ-caprolactone) (PLCL) core-shell nanofiber-coated film of stent, loaded with ethylene diamine tetraacetic acid and sodium cholate in core layer, was fabricated by co-axial electrospinning for treating gallstone disease. Image of laser scanning confocal microscopy and transmission electron microscopy demonstrated core-shell structure of drug-loaded nanofiber. Fourier transform infrared spectra and the thermogravimetric analysis proved ethylene diamine tetraacetic acid and sodium cholate to be successfully loaded in nanofibers. Morphology of nanofibers after a period of degradation still keeps good shape. Drugs can continuously release for around five days, which was proved significant effectiveness for dissolving gallstone. Besides, unobvious cytotoxicity was exhibited from MTT results and cell kept good morphology in vitro research. The present coated stent showed a bright prospect for dissolving the biliary stone., (© The Author(s) 2016.)

Lansoprazole (LSP), a proton-pump inhibitor, belongs to class II drug. It is especially instable to heat, light, and acidic media, indicating that fabrication of a formulation stabilizing the drug is difficult. The addition of alkaline stabilizer is the most powerful method to protect the drug in solid formulations under detrimental environment. The purpose of the study was to characterize the designed multiple coating pellets of LSP containing an alkaline stabilizer (sodium carbonate) and assess the effect of the stabilizer on the physicochemical properties of the drug. The coated pellets were prepared by layer-layer film coating with a fluid-bed coater. In vitro release and acid-resistance studies were carried out in simulated gastric fluid and simulated intestinal fluid, respectively. Furthermore, the moisture-uptake test was performed to evaluate the influence of sodium carbonate on the drug stability. The results indicate that the drug exists in the amorphous state or small (nanometer size) particles without crystallization even after storage at 40°C/75% for 5 months. The addition of sodium carbonate to the pellet protects the drug from degradation in simulated gastric fluid in a dose-dependent manner. The moisture absorbed into the pellets has a detrimental effect on the drug stability. The extent of drug degradation is directly correlated with the content of moisture absorption. In conclusion, these results suggest that the presence of sodium carbonate influence the physicochemical properties of LSP, and the designed multiple coating pellets enhance the drug stability.

Controlled-release drug delivery systems have many applications, including treatments for hormone deficiencies and chronic pain. A biodegradable device that could provide multi-dose drug delivery would be advantageous for long-term treatment of conditions requiring pulsatile drug release. In this work, biodegradable polymeric microchips were fabricated that released four pulses of radiolabelled dextran, human growth hormone or heparin in vitro. Heparin that was released over 142 days retained on average 96 +/- 12% of its bioactivity. The microchips were 1.2 cm in diameter, 480-560 microm thick and had 36 reservoirs that could each be filled with a different chemical. The devices were fabricated from poly(L-lactic acid) and had poly(D,L-lactic-co-glycolic acid) membranes of different molecular masses covering the reservoirs. A drug delivery system can be designed with the potential to release pulses of different drugs at intervals after implantation in a patient by using different molecular masses or materials for the membrane.

Amphiphilic block copolymers, poly(caprolactone)-poly(ethylene glycol)-poly(lactide) (PCELA), were synthesized by ring opening polymerization of caprolactone and lactide initiated with the hydroxyl groups of poly(ethylene glycol) (PEG). These copolymers could form micelle-like nanoparticles due to their amphiphilic characteristic. From the observation of transmission electron microscopy (TEM), the nanoparticles exhibited a regular spherical shape with core-shell structure. The critical micelle concentrations (CMC) of these nanoparticles in water were decreased as molecular weight of PEG decreased. The particle sizes obtained by dynamic light scattering of these nanoparticles were in the range of 100-200 nm, and increased as the hydrophobic property of the nanoparticles increased. Nimodipine as a model drug was loaded in these nanoparticles to investigate the drug release behavior. It was found that the chemical composition of the nanoparticles was a key factor in controlling nanoparticle size, nanoparticle yields, drug-entrapment efficiency, and drug release behavior. When the PEG content is about 2% (wt), the release profile of PCELA nanoparticles appeared to follow zero-order kinetics.

To accelerate the healing of bone defects or for healing to take place, it is often necessary to fill them with suitable substance. Various artificial materials defects have been developed. Among these, calcium phosphates and bioactive glass have been proven to be biocompatibile and bioactive materials that can chemically bond with bone, and have been successfully used clinically for repair of bone defects and augmentation of osseous tissue. However, those bioceramics have only the property of osteoconduction without any osteoinduction. Many ligands have been physicochemically absorbed onto substrates to enhance cell-substrate interactions. Although widely developed, they are still limited to use in long-term implantation because of their half-life period. Thus, some interfacial modification will be required for enhancing the efficacy of the delivery system. These models involve the immobilization of biologically active ligands of natural and synthetic origin onto various substrates to produce an interface with stronger chemical bond between ligand and substrate. The advantage of covalently immobilizing a ligand is that a chemical bond is present to prevent ligand or medicine from desorption. In our study, a two-step chemical immobilization was performed to surface-modified calcium hydrogenphosphate powders. The first was to modify the surface of calcium hydrogen-phosphate (CHP) with a coupling agent of hexanmethylene diisocyanate (HMDI). CHP surface modified by HMDI is abbreviated as MCHP. The linkage between CHP and HMDI will be characterized by FTIR. The second step was to immobilize chemically Gusuibu onto MCHP. Moreover, the sorption and desorption of Gusuibu was evaluated and quantitatively analyzed by spectrophotometer and HPLC. Bioceramic CHP was surface-modified by a two-step chemical immobilization. First, the surface of calcium hydrogen-phosphate (CHP) was successfully modified with coupling agent of hexanmethylene diisocyanate (HMDI). The first step was also activated the surface of CHP to induce primary amine terminator. The reaction of this functional group with Gusuibu was the second step. We confirmed simultaneously that Gusuibu could be immobilized chemically onto the surface of MCHP. Although some immobilized Gusuibu was also released rapidly at the first 12h, the degree of the released Gusuibu was lower than both by Gusuibu-adsorbing MCHP and Gusuibu-adsorbing CHP.