The intra-vascular stent as a site-specific local drug delivery system

The current review focuses on utilization of a tubular structure (coated or uncoated, balloon expandable or self expanding) known as a “stent” for localized intravascular drug delivery. Emphasis of the review is on technologies currently employed for immobilization and coating for drug onto the stent prior to its placement in various lumen of the body. A brief discussion on stent design, comparison of angioplasty and coronary stenting, and market status complements the review for researchers new to this area.     

Phosphorylcholine-based polymer coatings for stent drug delivery

Phosphorylcholine-based polymers have been used commercially to improve the biocompatibility of coronary stents. In this study, one particular polymer is assessed for its suitability as a drug delivery vehicle. Membranes of the material are characterized in terms of water content and molecular weight cut-off, and the presence of hydrophilic and hydrophobic domains investigated by use of the hydrophobic probe pyrene. The in vitro loading and elution of a variety of drugs was assessed using stents coated with the polymer. The rate of a drug's release was shown not to be simply a function of its water solubility, but rather more closely related to the drug oil/water partition coefficient. This finding was explained in terms of the more hydrophobic drugs partitioning into, and interacting with, the hydrophobic domains of the polymer coating. The suitability of the coated stent as a drug delivery vehicle was assessed in vivo using a radiolabeled analog of one of the more rapidly eluting drugs, angiopeptin. Autoradiography showed that the drug was released locally to the wall of the stented artery, and could be detected up to 28 days after implantation.     

Two-way shape memory effect in polymer laminates

Novel polymer laminate exhibiting two-way shape memory effect has been prepared by layer technique with the shape memory polymer and elastic polymer. In this paper, we demonstrate the two-way shape memory behavior, i.e., bending on heating and reverse bending on cooling; describe the preparation procedure; and investigate its two-way shape memory mechanism. Finally, it suggests that the mechanism can be ascribed to the release of elastic strain of shape memory polymer layer upon heating, and the elastic strain recovery induced by the bending force of substrate layer upon cooling.     

Interactive mixture as a rapid drug delivery system

The effectiveness of an interactive mixture as a rapid drug delivery system is compared with that of a solid dispersion. The influences of drug load, particle size, and crystallinity of these test systems are investigated. The interactive mixtures and solid dispersions were prepared from polyethylene glycol (PEG) 3350 and hydrophobic nifedipine drug by means of physical mixing and melting methods, respectively. The formed products were subjected to drug particle size and crystallinity analyses, and dissolution tests. In comparison with the interactive mixtures, the solid dispersions with low drug load were more effective as a rapid drug delivery system, as the size of a given batch of drug particles was markedly reduced by the molten PEG 3350. The rate and extent of drug dissolution were mainly promoted by decreasing effective drug particle size. However, these were lower in the solid dispersions than in the interactive mixtures when a high load of fine drug particles was used as the starting material. This was attributed to drug coarsening during the preparation of the solid dispersion. Unlike solid dispersions, the interactive mixtures could accommodate a high load of fine drug particles without compromising its capacity to enhance the rate and extent of drug dissolution. The interactive mixture is appropriate for use to deliver a fine hydrophobic drug in a formulation requiring a high drug load.     

Unique aspects of a shape memory polymer as the substrate for surface wrinkling

Typical bilayer wrinkle systems employ soft elastomers as the substrates. In contrast, shape memory polymers have recently emerged as attractive alternatives. Besides the shape fixing capability, shape memory polymers distinguish from elastomers in that they are rigid at room temperature, but experience significant modulus drop upon heating. We hereby report unique aspects of shape memory polymers as the wrinkle substrate utilizing a metallic thin film as the top layer. The feasibility to create both reversible and irreversible wrinkles (and diffraction colors) on a single substrate is demonstrated. Experimental conditions are identified to create crack free wrinkles and the impact of various experimental parameters on the wrinkle wavelength and amplitude is investigated. The results suggest that the wrinkle mechanics deviate notably from the existing theories established with elastomers as the wrinkle substrates. Thus, a new theory will need to be developed in the future, taking into account of unique thermomechanical properties of the shape memory substrate and possible plastic deformation of the thin film.     

Porous pellets as drug delivery system

Background: Multiparticulate drug delivery systems, such as pellets, are frequently used as they offer therapeutic advantages over single-unit dosage forms. Aim: Development of porous pellets followed by evaluation of potential drug loading techniques. Method: Porous microcrystalline pellets were manufactured and evaluated as drug delivery system. Pellets consisting of Avicel PH 101 and NaCl (70%, w/w) were prepared by extrusion/spheronization. The NaCl fraction was extracted with water and after drying porous pellets were obtained (33.2% porosity). Immersion of the porous pellets in a 15% and 30% (w/v) metoprolol tartrate solution, ibuprofen impregnation via supercritical fluids and paracetamol layering via fluidized bed coating were evaluated as drug loading techniques. Results: Raman spectroscopy revealed that immersion of the pellets in a drug solution and supercritical fluid impregnation allowed the drug to penetrate into the porous structure of the pellets. The amount of drug incorporated depended on the solubility of the drug in the solvent (water or supercritical CO₂). Drug release from the porous pellets was immediate and primarily controlled by pure diffusion. Conclusion: The technique described in this research work is suitable for the production of porous pellets. Drug loading via immersion the pellets in a drug solution and supercritical fluid impregnation resulted in a drug deposition in the entire pellet in contrast to fluid bed layering where drugs were only deposed on the pellet surface.     

A Two-network thermomechanical model of a shape memory polymer

The aim of this work is to demonstrate a Helmholtz potential based approach for the development of the constitutive equations for a shape memory polymer undergoing a thermomechanical cycle. The model is able to simulate the response of the material during heating and cooling cycles and the sensitive dependence of the response on thermal expansion. We notice that the yield-stress of the material controls the gross features of the response of the model, and suggests that the material yields differently depending on not just the current value of the temperature but also on whether the temperature of the material dropped or increased from the previous time-step somewhat similar to the Bauschinger effect in plasticity, except that here the controlling parameter is the rate of temperature change rather than rate of plastic strain. The results of the simulation are in qualitative and quantitative agreement with experiments performed on two different shape memory polymer samples: polyurethane and epoxy resin. We find that modeling the hysteresis of the yield stress of the material during temperature changes is the key to the results.     

Intrinsic two-way shape memory effect in a Ni-Mn-Sn metamagnetic shape memory microwire

An intrinsic two-way shape memory effect with a fully recoverable strain of 1.0% was achieved in an as-prepared Ni_(50)Mn_(37.5)Sn_(12.5) metamagnetic shape memory microwire fabricated by Taylor-Ulitovsky method. This two-way shape memory effect is mainly owing to the internal stress caused by the retained martensite in austenite matrix, as revealed by transmission electron microscopy observations and highenergy X-ray diffraction experiments. After superelastic training for 30 loading/unloading cycles at room temperature, the amount of retained martensite increased and the recoverable strain of two-way shape memory effect increased significantly to 2.2%. Furthermore, a giant recoverable strain of 11.2% was attained under a bias stress of 300 MPa in the trained microwire. These properties confer this microwire great potential for micro-actuation applications.     

Development of a miniaturised drug delivery system with wireless power transfer and communication

The development of an implantable system designed to deliver drug doses in a controlled manner over an extended time period is reported. Key performance parameters are the physical size, the power consumption and also the ability to perform wireless communications to enable the system to be externally controlled and interrogated. The system has been designed to facilitate wireless power transfer, which is very important for miniaturisation as it removes the need for a battery.     

Physical characterization of polymer electrolytes as novel iontophoretic drug delivery devices

Polymer electrolytes are solidlike materials formed by dispersing a salt at the molecular level in a high molecular weight polymer such as poly(ethylene oxide) (PEO). They have been extensively studied for use in electrochemical applications such as batteries and display devices. This paper considers a novel application of polymer electrolytes as the basis of iontophoretic drug delivery systems. Polymer electrolyte films were cast from solutions of PEO and various drug salts using either water or an acetonitrile/ethanol mixture as the solvent. These films were characterized by variable-temperature polarizing microscopy (VTPM), differential scanning calorimetry (DSC), and alternating current (AC) impedance analysis. The films were around 100-μm thick and mechanically strong; the optical and thermal methods provided evidence that the polymer electrolytes had crystalline and amorphous phases, although some drugs may exist in films as nanodispersions. The amorphous phase is important as ions have greater mobility in this phase and therefore allow a current to be passed when the material is incorporated into a device such as one suitable for drug delivery by iontophoresis. The AC impedance analysis showed that the conductivity of the films varied between 10^-6 and 10^-3 S cm^-1, depending on the salt, casting solvent, and temperature. Two drugs in particular were shown to be promising candidates in these systems: lidocaine hydrochloride and lithium chloride.     

TiNiCu形状记忆合金双向记忆效应研究

研究了热机械训练温度及定型处理温度对TiNiCu形状记忆合金弹簧双向记忆效应的影响。研究结果表明:在纯马氏体状态进行训练时,双向记忆恢复率随训练次数的增加而增加,并在一定的训练次数后达到饱和;在纯奥氏体状态进行训练,双向记忆恢复率随训练次数迅速增加到某一最大值后随训练次数的增加而减小;在马氏体和奥氏体混合相进行训练时,双向记忆恢复率随训练次数先增加而后减小。经过400～550℃×1h/AC定型处理及热机械训练后最大形状记忆恢复率随定型处理温度升高先增大然后减小。由于马氏体再取向时引入的位错有利于双向记忆效应,热诱发和应力诱发的马氏体变体数量不同,引起了在不同状态训练诱发的双向记忆效应随训练次数变化的差异。     

Synthesis and characterization of a novel biodegradable thermoplastic shape memory polymer

A novel poly(urethane-urea) shape memory polymer (PUU SMP) was synthesized from poly(DL-lactic acid) (PDLLA) Diols, hexamethylene diisocyanate(HDI) and butanediamine(BDA), aiming to develop a biodegradable and biocompatible shape memory polymer. Its structure, thermal properties and shape-memory behaviors were characterized through Fourier transform infrared spectrometry (FTIR), differential scanning calorimetry (DSC) and bending test. The results showed that the response temperature for shape memory of PDLLA–PUU SMP is dependent on the polymeric glass transition temperature and this polymer has an excellent shape memory effect, having the ratio of the shape-memory fixation approximately 100% and the ratio of the shape-memory recovery about 98%.     

Development and physico-mechanical characterization of carrageenan and poloxamer-based lyophilized matrix as a potential buccal drug delivery system

Context and objectives: The buccal mucosa presents a unique surface for non-invasive drug delivery and also avoids first-pass metabolism. The objective of this study was the formulation development of polymeric mucoadhesive lyophilized wafers as a matrix for potential buccal drug delivery.

Materials and methods: Differential scanning calorimetry (DSC) was used to develop an optimum freeze-cycle, incorporating an annealing step. The wafers were prepared by lyophilization of gels containing three polymers, κ-carrageenan (CAR 911), poloxamer (P407) and polyethylene glycol 600 (PEG 600). The formulations were characterized using texture analysis (for mechanical and mucoadhesion properties), hydration studies, thermogravimetric analysis (TGA), DSC, X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM).

Results and discussion: DSC showed the eutectic temperature (12.8?°C) of the system where the liquid solution and pure solids both existed at a fixed pressure which helped determine the freeze-annealing cycle at 55?°C for 7?h. Mechanical resistance to compression, hydration and mucoadhesion studies showed that optimized wafers were obtained from aqueous gels containing 2% w/w CAR 911, 4% w/w P407 and 4.4% w/w PEG 600. TGA showed residual water of approximately 1% and SEM showed a porous polymeric network that made ease of hydration possible.

Conclusions: Lyophilized wafers by freeze-drying gels containing 2% w/w CAR 911, 4% w/w P407 and 4.4% w/w PEG 600 with optimum physico-mechanical properties has been achieved.     

Influence of natural polymer coating on novel colon targeting drug delivery system

A novel colon targeted tablet formulation was developed using natural polysaccharides such as chitosan and guar gum as carriers and diltiazem hydrochloride as model drug. The prepared blend of polymer-drug tablets were coated with two layers, inulin as an inner coat followed by shellac as outer coat and were evaluated for properties such as average weight, hardness and coat thickness. In vitro release studies of prepared tablets were carried out for 2 h in pH 1.2 HCl buffer, 3 h in pH 7.4 phosphate buffer and 6 h in simulated colonic fluid (SCF) in order to mimic the conditions from mouth to colon. It was observed that 4% w/v of rat cecal contents in saline phosphate buffer (SCF) incubated for 24 h provides suitable conditions for in vitro evaluation of the formulations prepared. The drug release from the coated system was monitored using UV/ Visible spectroscopy. In vitro studies revealed that the tablets coated with inulin and shellac have controlled the drug release in stomach and small intestinal environment and released maximum amount of drug in the colonic environment. Among the polymers used, chitosan was found to be the suitable polymer for colon targeting. The study revealed that polysaccharides as carriers and inulin and shellac as coating materials can be used effectively for colon targeting of drugs for treating local as well as systemic disorders.     

Degeneration and rejuvenation of shape memory effect associated with the precipitation of coherent nano-particles in a Co-Ni-Si shape memory alloy

In a solution treated Co-20Ni-6Si shape memory alloy,coherent nano-particles were precipitated after annealing at 873 K for 1 min,but the shape memory effect almost vanished.It is attributed to that the coherent nano-particles not only suppressed the stress-induced face-centered cubic to close-packed hexagonal martensite transformation but also damaged the crystallographic reversibility of reverse martensite transformation.After further annealing at 1073 K for 1 min,the shape memory effect was reju-venated owing to the dissolution of nano-particles.Besides,the recovery strain significantly increased to 5.1％ from the solution treatment of 3.1％ after annealing at 1073 K for 1 min.     

The recovery properties under load of a shape memory polymer composite material

In many applications, shape memory alloys are being replaced by shape memory polymers as they have some better properties than shape memory alloys. Nevertheless, shape memory alloys can recover under load which shape memory polymers cannot. Shape memory polymers are not capable of giving full recovery even lifting a tiny load. The melting temperature or the glass transition temperature is the transition temperatures to which shape memory polymers are closely heated. Then a deforming force up to a certain position is applied to the heated shape memory polymers. After that shape memory polymer is permitted to cool while keeping it deformed. After the cooling, shape memory polymer obtains the temporary shape which can be recovered by reheating it at the similar transition temperature (glass transition or melting). Consequently, it recovers at its initial state. Shape memory polymer can achieve constrained recovery and unconstrained recovery, nonetheless; under stress, it is partly recovered. In current work, recovery under load has been investigated of an asymmetrical shape memory composite. It is established that it is capable to recover under various loads. Under various loads, it shows full recovery in reference to initial state. The ability to recover under load can be potentially used in diverse applications.     

On the cyclic material stability of shape memory polymer

This paper presents the experimental study of a Thermoplastic Polyurethane (TPU) based Shape Memory Polymer (SMP) produced from granulates of commercially available Estane^TM ETE75DT3 NAT022 (Oevel Westerlo, Belgium). This polymer is characterized by Differential Scanning Calorimetry (DSC) and Dynamic Mechanical Thermal Analysis (DMTA). The experimental procedure was designed to study the functional properties (shape fixity and shape recovery) of this shape memory polymer in multiple programming/shape‐recovery cycles at three different programming temperatures. The results are displayed in the temperature‐stress‐strain space with focus on parameters which characterize the functional fatigue and material stability of the tested polymer during consecutive cycles. These results give a better understanding of this material class that has a potential for actuator applications in engineering.