Traditional drugs are facing bottlenecks of lower solubility, absorption, and especially the inefficient organs or cells targeting during the precision medicine era. It is urgently needed to discover and establish new methods or strategies to modify old drugs or create new ones against the above defects. With the support of nanotechnology, the solubility, absorption and targeting of traditional drugs were greatly improved by modifying and fabricating with various types of nanoparticles to some extent, though many shortages remain. In this mini-review we will focus on advances in several most commonly used nanoparticles, from their nature and design, to drug delivery system and clinical application, that they overcome heterogeneous barriers in precision medicine, thereby ultimately improve patient outcome overall. 相似文献
Important classes of drugs have yet to benefit from advances in drug delivery technology. Strategies to provide reasonable oral bioavailability of peptide and proteins drugs remain elusive, for example. Systemic cancer drugs produce dose-limiting toxicities largely due to their lack of selectivity. Although delivery systems such as immunotoxins and liposomes improve selectivity of a few cancer drugs, current technology is not suitable for the vast majority of such molecules. Systems able to mimic the body's natural feedback mechanisms for secretion of hormones such as insulin represents yet another unmet medical need. Microfabrication techniques may permit the creation of drug delivery systems that possess a combination of structural, mechanical, and perhaps electronic features which may surmount some of these challenges. In this review, drug delivery concepts are presented which capitalize on the strengths of microfabrication. Possible applications include micromachined silicon membranes to create implantable biocapsules for the immunoisolation of pancreatic islet cells—as a possible treatment for diabetes—and sustained release of injectable drugs needed over long time periods. Asymmetrical, drug-loaded microfabricated particles with specific ligands linked to the surface are proposed for improving oral bioavailability of peptide (and perhaps protein) drugs. Similarly designed particles with sizes in the 2–10 m range may be safe to administer intravenously and a clinical strategy is suggested for using such microparticles for treating solid tumors. Although hypothetical now, work is in progress to prove the concepts presented here and to validate the intuitive belief that there is an important place for microfabricated systems in drug delivery. 相似文献
Transdermal drug delivery systems (TDDSs) overcome the hurdle of an intact skin barrier by penetrating the skin to allow molecules through. These systems reduce side effects associated with conventional hypodermic needles. Here, we introduce novel microneedle (MN) TDDSs that enhance drug delivery by creating micron-sized pores across the skin. Many MN TDDSs designed to deliver a diverse array of therapeutics, including allergen-specific immunotherapy, skin disease treatments, and vaccines, are under pre-clinical and clinical trials. Although epicutaneous approaches are emerging as new options for treating food allergy in many clinical trials, MN TDDSs could provide a more efficient and convenient route to deliver macromolecules. Furthermore, MN TDDSs may allow for safe vaccine delivery without permanent scars. MN TDDSs are a major emerging strategy for delivering novel vaccines and treatments for diseases, including skin diseases, allergic diseases, and so on. 相似文献
We designed and fabricated an array of sugar micro needles of the length ranging from 150 μ m to 2 mm for transdermic delivery of drugs. Micro needles were molded out of maltose mixed with pharmaceutical material, being expected bio-degradable in the human skin. To test basic tolerance to the healthy human skin, a clinical experiment was carried out for 10 healthy adult volunteers. 500 μ m-needles containing 5 wt% of ascorbate-2-glycoside were inserted into the skin of the forearm and snapped off to be left in the skin. They spontaneously dissolved by hydrolysis to release ascorbate in the epidermis and the dermis. No dermatological problems were observed in terms of the International Contact Dermatitis Research Group criteria. These observations indicate that the present system is a novel approach to achieve transdermic drug delivery. 相似文献
Microneedles are promising microfabricated devices for minimally invasive drug delivery applications. Needles can be integrated into a variety of devices. However, any portable drug delivery device with integrated microneedles will need an equally compact means to deliver therapeutics. This work presents microneedles integrated with an on-chip MEMS positive displacement micropump for continuous drug delivery applications. The generation and collapse of thermally generated bubbles with flow rectified by directional check valves are used to achieve net pumping through the device. Visualization methods have observed net flow rates of water out of a microneedle at approximately 2.0 nl/s with a pressure of 3.9 kPa. In addition, continuous pumping was achieved for more than 6 hours with the heaters actuating for over 18 hours (15,000 cycles) without failing. 相似文献
Local delivery of anti-thrombotic and anti-restenotic drugs is desired to achieve high concentrations of agents which may be rapidly degraded systemically or which exhibit very short half-lives in vivo. In this article, the operating characteristics of a novel local drug delivery method are described and its effectiveness demonstrated computationally and experimentally. Computational models used a finite volume method to determine the concentration field. Optical dye density measurements of Evans blue in saline were performed in an in vitro steady flow system. Modeling parameters were kept in the physiologic range. Experimental flow visualization studies demonstrated high concentrations of infusate near the vessel wall. Computational studies predicted high, clinically significant drug concentrations along the wall downstream of the infusion device. When the radial infusion velocity is large (infusion flow rate, Qinf > 0.5% of the main flow rate, Q), the wall concentration of the infused drug remains high, e.g., levels are greater than 80% of the infusate concentration 5 cm downstream of the infusion device. At lower infusion rates (Qinf < 0.001Q), the drug concentration at the wall decreases exponentially with axial distance to less than 25% of the infusate concentration 5 cm downstream of the infusion device, although therapeutic drug levels are still readily maintained. The near wall drug concentration is a function of flow conditions, infusion rate, and the drug diffusivity. Good agreement was obtained between computational and experimental concentration measurements. Flow simulation and experimental results indicate that the technique can effectively sustain high local drug concentrations for inhibition of thrombosis and vascular lesion formation. 相似文献
Methoxy PEG amine with molecular weight of 5k and ε‐caprolactone with molecular weight of 1 960 were conjugated to a peptide comprising three cysteine residues. The shift of peak molecular weight and narrow molecular weight distribution in GPC trace without any noticeable shoulder as well as 1H NMR analysis confirmed the successful synthesis of the copolymer. A modified O/W dialysis system was employed to prepare self‐aggregates having the size around 210 nm. During the dialysis, stabilized aggregates were obtained by intermolecular disulfide bonds via oxidation. Critical aggregate concentration (CAC) of the copolymer was determined as 0.07 mg · mL?1 and disulfide‐stabilized self‐aggregates remained stable regardless of the concentration without displaying CAC. Doxorubicin‐loading amount and efficiency was 8.7 and 26.0%, respectively. Release profile of doxorubicin below CAC at 37 °C showed a sustained release and the addition of D ,L ‐dithiothreitol (DTT) after 24 h triggered a burst release of doxorubicin. Intermolecular disulfide bonds via oxidation stabilized the polymeric aggregates even in the diluted condition similar to that in the bloodstream and addition of DTT destabilized the aggregates to burst encapsulated doxorubicin in the reductive condition.