Regulate e-cigarettes as drug-delivery devices.
Ontology highlight
ABSTRACT:
SUBMITTER: Stanbrook MB
PROVIDER: S-EPMC3826374 | biostudies-literature | 2013 Nov
REPOSITORIES: biostudies-literature
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Project description:We demonstrate a novel structure based on smart carbon nanocomposites intended for fabricating laser-triggered drug delivery devices (DDDs). The performance of the devices relies on nanocomposites' photothermal effects that are based on polydimethylsiloxane (PDMS) with carbon nanoparticles (CNPs). Upon evaluating the main features of the nanocomposites through physicochemical and photomechanical characterizations, we identified the main photomechanical features to be considered for selecting a nanocomposite for the DDDs. The capabilities of the PDMS/CNPs prototypes for drug delivery were tested using rhodamine-B (Rh-B) as a marker solution, allowing for visualizing and quantifying the release of the marker contained within the device. Our results showed that the DDDs readily expel the Rh-B from the reservoir upon laser irradiation and the amount of released Rh-B depends on the exposure time. Additionally, we identified two main Rh-B release mechanisms, the first one is based on the device elastic deformation and the second one is based on bubble generation and its expansion into the device. Both mechanisms were further elucidated through numerical simulations and compared with the experimental results. These promising results demonstrate that an inexpensive nanocomposite such as PDMS/CNPs can serve as a foundation for novel DDDs with spatial and temporal release control through laser irradiation.
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Project description:Dry powder inhalers (DPIs) are an important and increasingly investigated method of modern therapy for a growing number of respiratory diseases. DPIs are a promising option for certain patient populations, and may help to overcome several limitations that are associated with other types of inhalation delivery systems (e.g., accuracy and reproducibility of the dose delivered, compliance and adherence issues, or environmental aspects). Today, more than 20 different dry powder inhalers are on the market to deliver active pharmaceutical ingredients (APIs) for local and/or systemic therapy. Depending on the mechanism of deagglomeration, aerosolization, dose metering accuracy, and the interpatient variability, dry powder inhalers demonstrate varying performance levels. During development, manufacturers focus on improving aspects characteristic of their specific DPI devices, depending on the intended type of application and any particular requirements associated with it. With the wide variety of applications related to specific APIs, there exists a range of different devices with distinct features. In addition to the routinely used multi-use DPIs, several single-use disposable devices are under development or already approved. The recent introduction of disposable devices will expand the range of possible applications for use by including agents such as vaccines, analgesics, or even rescue medications. This review article discusses the performance and advantages of recently approved dry powder inhalers as well as disposable single-use inhalers that are currently under development.
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Project description:A reservoir that could be remotely triggered to release a drug would enable the patient or physician to achieve on-demand, reproducible, repeated, and tunable dosing. Such a device would allow precise adjustment of dosage to desired effect, with a consequent minimization of toxicity, and could obviate repeated drug administrations or device implantations, enhancing patient compliance. It should exhibit low off-state leakage to minimize basal effects, and tunable on-state release profiles that could be adjusted from pulsatile to sustained in real time. Despite the clear clinical need for a device that meets these criteria, none has been reported to date to our knowledge. To address this deficiency, we developed an implantable reservoir capped by a nanocomposite membrane whose permeability was modulated by irradiation with a near-infrared laser. Irradiated devices could exhibit sustained on-state drug release for at least 3 h, and could reproducibly deliver short pulses over at least 10 cycles, with an on/off ratio of 30. Devices containing aspart, a fast-acting insulin analog, could achieve glycemic control after s.c. implantation in diabetic rats, with reproducible dosing controlled by the intensity and timing of irradiation over a 2-wk period. These devices can be loaded with a wide range of drug types, and therefore represent a platform technology that might be used to address a wide variety of clinical indications.
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Project description:Electrospun nanofibers are a 3D scaffold of choice for many drug delivery devices due to their high surface area, significant capacity for drug payload, ease of in situ placement, and scalable manufacture. Herein, we report the synthesis of polymeric, pH-responsive nanofiber buttresses via electrospinning. The homopolymer is comprised of an acrylic backbone with acid-sensitive, hydrolyzable, trimethoxybenzaldehyde-protected side chains that lead to buttress transformation from a hydrophobic to a hydrophilic state under physiologically relevant pH conditions (e.g., extracellular tumor environment with pH = 6.5). Hydrolysis of the side chains leads to an increase in fiber diameter from approximately 350 to 900 nm and the release of the encapsulated drug cargo. In vitro drug release profiles demonstrate that significantly more drug is released at pH 5.5 compared to pH 7.4, thereby limiting the release to the target site, with docetaxel releasing over 20 days and doxorubicin over 7 days. Drug burst release, defined as >50% within 24 hours, does not occur at either pH or with either drug. Drug-loaded buttresses preserve drug activity and are cytotoxic to multiple human cancer lines, including breast and lung. Important to their potential application in surgical applications, the tensile strength of the buttresses is 6.3 kPa and, though weaker than commercially available buttresses, they provide sufficient flexibility and mechanical integrity to serve as buttressing materials via the application with a conventional surgical cutting stapler.
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Project description:Electrophoretic drug delivery devices are able to deliver drugs with exceptional temporal and spatial precision. This technology has emerged as a promising platform for treating pathologies ranging from neuropathic pain to epilepsy. As the range of applications continues to expand, there is an urgent need to understand the underlying physics and estimate materials and device parameters for optimal performance. Here, computational modeling of the electrophoretic drug delivery device is carried out. Three critical performance indices, namely, the amount of drug transported, the pumping efficiency and the ON/OFF ratio are investigated as a function of initial drug concentration in the device and fixed charge concentration in the ion exchange membrane. The results provide guidelines for future materials and device design with an eye towards tailoring device performance to match disease-specific demands.
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Project description:Glaucoma is a group of heterogeneous disorders involving progressive optic neuropathy that can culminate into visual impairment and irreversible blindness. Effective therapeutic interventions must address underlying vulnerability of retinal ganglion cells (RGCs) to degeneration in conjunction with correcting other associated risk factors (such as elevated intraocular pressure). However, realization of therapeutic outcomes is heavily dependent on suitable delivery system that can overcome myriads of anatomical and physiological barriers to intraocular drug delivery. Development of clinically viable sustained release systems in glaucoma is a widely recognized unmet need. In this regard, implantable delivery systems may relieve the burden of chronic drug administration while potentially ensuring high intraocular drug bioavailability. Presently there are no FDA-approved implantable drug delivery devices for glaucoma even though there are several ongoing clinical studies. The paper critically assessed the prospects of polymeric implantable delivery systems in glaucoma while identifying factors that can dictate (a) patient tolerability and acceptance, (b) drug stability and drug release profiles, (c) therapeutic efficacy, and (d) toxicity and biocompatibility. The information gathered could be useful in future research and development efforts on implantable delivery systems in glaucoma.
| S-EPMC3770064 | biostudies-other
Project description:Implantable electrophoretic drug delivery devices have shown promise for applications ranging from treating pathologies such as epilepsy and cancer to regulating plant physiology. Upon applying a voltage, the devices electrophoretically transport charged drug molecules across an ion-conducting membrane out to the local implanted area. This solvent-flow-free "dry" delivery enables controlled drug release with minimal pressure increase at the outlet. However, a major challenge these devices face is limiting drug leakage in their idle state. Here, a method of reducing passive drug leakage through the choice of the drug co-ion is presented. By switching acetylcholine's associated co-ion from chloride to carboxylate co-ions as well as sulfopropyl acrylate-based polyanions, steady-state drug leakage rate is reduced up to sevenfold with minimal effect on the active drug delivery rate. Numerical simulations further illustrate the potential of this method and offer guidance for new material systems to suppress passive drug leakage in electrophoretic drug delivery devices.
| S-EPMC8224430 | biostudies-literature
Project description:Microneedles are a relatively simple, minimally invasive and painless approach to deliver drugs across the skin. However, there remain limitations with this approach because of the materials most commonly utilized for such systems. Silk protein, with tunable and biocompatibility properties, is a useful biomaterial to overcome the current limitations with microneedles. Silk devices preserve drug activity, offer superior mechanical properties and biocompatibility, can be tuned for biodegradability, and can be processed under aqueous, benign conditions. In the present work, the fabrication of dense microneedle arrays from silk with different drug release kinetics is reported. The mechanical properties of the microneedle patches are tuned by post-fabrication treatments or by loading the needles with silk microparticles, to increase capacity and mechanical strength. Drug release is further enhanced by the encapsulation of the drugs in the silk matrix and coating with a thin dissolvable drug layer. The microneedles are used on human cadaver skin and drugs are delivered successfully. The various attributes demonstrated suggest that silk-based microneedle devices can provide significant benefit as a platform material for transdermal drug delivery.
| S-EPMC3883884 | biostudies-literature
Project description:BackgroundTechnologies in which a remote trigger is used to release drug from an implanted or injected device could enable on-demand release profiles that enhance therapeutic effectiveness or reduce systemic toxicity. A number of new materials have been developed that exhibit sensitivity to light, ultrasound, or electrical or magnetic fields. Delivery systems that incorporate these materials might be triggered externally by the patient, parent or physician to provide flexible control of dose magnitude and timing.ObjectivesTo review injectable or implantable systems that are candidates for translation to the clinic, or ones that have already undergone clinical trials. Also considered are applicability in pediatrics and prospects for the future of drug delivery systems.MethodsWe performed literature searches of the PubMed and Science Citation Index databases for articles in English that reported triggerable drug delivery devices, and for articles reporting related materials and concepts.ResultsApproaches to remotely-triggered systems that have clinical potential were identified. Ideally, these systems have been engineered to exhibit controlled on-state release kinetics, low baseline leak rates, and reproducible dosing across multiple cycles.ConclusionsAdvances in remotely-triggered drug delivery have been brought about by the convergence of numerous scientific and engineering disciplines, and this convergence is likely to play an important part in the current trend to develop systems that provide more than one therapeutic modality. Preclinical systems must be carefully assessed for biocompatibility, and engineered to ensure pharmacokinetics within the therapeutic window. Future drug delivery systems may incorporate additional modalities, such as closed-loop sensing or onboard power generation, enabling more sophisticated drug delivery regimens.
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Project description:Receptor-mediated endocytosis (RME) has been extensively studied as a method for augmenting the transport of therapeutic devices across monolayers. These devices range from simple ligand-therapeutic conjugates to complex ligand-nanocarrier systems. However, characterizing the uptake of these carriers typically relies on their comparisons to the native therapeutic, which provides no understanding of the ligand or cellular performance. To better understand the potential of the RME pathway, a model for monolayer transport was designed based on the endocytosis cycle of transferrin, a ligand often used in RME drug-delivery devices. This model established the correlation between apical receptor concentration and transport capability. Experimental studies confirmed this relationship, demonstrating an upper transport limit independent of the applied dose. This contrasts with the dose-proportional pathways that native therapeutics rely on for transport. Thus, the direct comparison of these two transport mechanisms can produce misleading results that change with arbitrarily chosen doses. Furthermore, transport potential was hindered by repeated use of the RME cycle. Future studies should base the success of this technology not on the performance of the therapeutic itself, but on the capabilities of the cell. Using receptor-binding studies, we were able to demonstrate how these capabilities can be predicted and potentially adopted for high-throughput screening methods.
| S-EPMC4441268 | biostudies-literature