Effective eye drop delivery systems for treating diseases of the posterior segment have yet to be clinically validated. Further, adherence to eye drop regimens is often problematic due to the difficulty and inconvenience of repetitive dosing. Here, we describe a strategy for topically dosing a peptide-drug conjugate to achieve effective and sustained therapeutic sunitinib concentrations to protect retinal ganglion cells (RGCs) in a rat model of optic nerve injury.
View Article and Find Full Text PDFSustained drug delivery strategies have many potential benefits for treating a range of diseases, particularly chronic diseases that require treatment for years. For many chronic ocular diseases, patient adherence to eye drop dosing regimens and the need for frequent intraocular injections are significant barriers to effective disease management. Here, we utilize peptide engineering to impart melanin binding properties to peptide-drug conjugates to act as a sustained-release depot in the eye.
View Article and Find Full Text PDFWhile eye drops are the most common ocular dosage form, eye drops for treating diseases of the posterior segment (retina, choroid, optic nerve) have yet to be developed. In glaucoma, eye drops are used extensively for delivering intraocular pressure (IOP)-lowering medications to the anterior segment. However, degeneration of retinal ganglion cells (RGCs) in the retina may progress despite significant IOP lowering, suggesting that a complementary neuroprotective therapy would improve glaucoma management.
View Article and Find Full Text PDFAdv Ther (Weinh)
February 2021
We here introduce a new paradigm to promote pulmonary DNA vaccination. Specifically, we demonstrate that nanoparticles designed to rapidly penetrate airway mucus (mucus-penetrating particle or MPP) enhance the delivery of inhaled model DNA vaccine (i.e.
View Article and Find Full Text PDFSkin vaccination by microneedle (MN) patch simplifies the immunization process to increase access to vaccines for global health. Lyophilization has been widely used to stabilize vaccines and other biologics during storage, but is generally not compatible with the MN patch manufacturing processes. In this study, our goal was to develop a method to incorporate lyophilized inactivated H1N1 influenza vaccine into MN patches during manufacturing by suspending freeze-dried vaccine in anhydrous organic solvent during the casting process.
View Article and Find Full Text PDFBackground: With increasing life expectancy, stem cell therapy is receiving increasing attention. However, its application is restricted by ethical concerns. Hence a need exists for design of safe procedures for stem cell procurement.
View Article and Find Full Text PDFEye-drop formulations should hold as high a concentration of soluble drug in contact with ocular epithelium for as long as possible. However, eye tears and frequent blinking limit drug retention on the ocular surface, and gelling drops typically form clumps that blur vision. Here, we describe a gelling hypotonic solution containing a low concentration of a thermosensitive triblock copolymer for extended ocular drug delivery.
View Article and Find Full Text PDFHypoxia-inducible factor-1 (HIF-1) has been implicated in the pathogenesis of choroidal neovascularization (NV) and is an appealing target because it increases multiple pro-angiogenic proteins and their receptors. Acriflavine (ACF) binds HIF-1α and HIF-2α preventing binding to HIF-1β and inhibiting transcriptional activity of HIF-1 and HIF-2. Delivery of ACF to the eye by multiple routes strongly, but transiently, suppresses choroidal NV.
View Article and Find Full Text PDFMedicine (Baltimore)
December 2018
Rationale: Large soft tissue defects on the lower back represent a treatment challenge. Among a variety of reconstructive procedures, the latissimus dorsi (LD) muscle or musculocutaneous flap is one of most frequently used pedicled flaps. However, the pedicled LD flap carries a bulky pivot point and a short arc of rotation.
View Article and Find Full Text PDFMicroneedle injection into the suprachoroidal space (SCS) enables targeted drug delivery for treatment of posterior segment diseases. This study sought to identify and characterize anatomical barriers to circumferential spread of particles in the SCS of rabbit and human cadaver eyes. These barriers could make targeting specific regions within the SCS challenging.
View Article and Find Full Text PDFIn this work, we tested the hypothesis that particles injected into the suprachoroidal space can be localized at the site of injection or broadly distributed throughout the suprachoroidal space by controlling polymeric formulation properties. Single hollow microneedles were inserted into the sclera of New Zealand White rabbits and injected non-biodegradable fluorescently tagged nanoparticles and microparticles suspended in polymeric formulations into the suprachoroidal space of the eye. When formulated in saline, the particles were distributed over 29-42% of the suprachoroidal space immediately after injection.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
September 2014
Purpose: In this work, we tested the hypothesis that highly targeted delivery of antiglaucoma drugs to the supraciliary space by using a hollow microneedle allows dramatic dose sparing of the drug compared to topical eye drops. The supraciliary space is the most anterior portion of the suprachoroidal space, located below the sclera and above the choroid and ciliary body.
Methods: A single, hollow 33-gauge microneedle, 700 to 800 μm in length, was inserted into the sclera and used to infuse antiglaucoma drugs into the supraciliary space of New Zealand white rabbits (N = 3-6 per group).
Invest Ophthalmol Vis Sci
September 2014
Purpose: This study tested the hypothesis that highly targeted intrastromal delivery of bevacizumab using coated microneedles allows dramatic dose sparing compared with subconjunctival and topical delivery for treatment of corneal neovascularization.
Methods: Stainless steel microneedles 400 μm in length were coated with bevacizumab. A silk suture was placed in the cornea approximately 1 mm from the limbus to induce corneal neovascularization in the eyes of New Zealand white rabbits that were divided into different groups: untreated, microneedle delivery, topical eye drop, and subconjunctival injection of bevacizumab.
Jaw fracture surgery or orthognathic surgery usually involves the application of an intermaxillary fixation (IMF). Obstructions that cannot be relieved by suction require an immediate release of IMF wires, but releasing the IMF may damage the surgical alignment of the facial bones. The mean time taken to release the jaws was an average of 2 minutes 9 seconds by hospital staff involved in caring for these patients.
View Article and Find Full Text PDFBiopharmaceuticals are making increasing impact on medicine, including treatment of indications in the eye. Macromolecular drugs are typically given by physician-administered invasive delivery methods, because non-invasive ocular delivery methods, such as eye drops, and systemic delivery, have low bioavailability and/or poor ocular targeting. There is a need to improve delivery of biopharmaceuticals to enable less-invasive delivery routes, less-frequent dosing through controlled-release drug delivery and improved drug targeting within the eye to increase efficacy and reduce side effects.
View Article and Find Full Text PDFThis study tests the hypothesis that high-density particle-stabilized emulsion droplets (PEDs) can be designed to use gravity to target specific locations in the eye via suprachoroidal space injection. PEDs contain a core of high-density perfluorodecalin measuring ≤35 μm in diameter surrounded and stabilized by fluorescein-tagged, polystyrene nanoparticles that simulate polymeric drug carriers. A hollow microneedle infuses PEDs into the suprachoroidal space of rabbit eyes in vivo, which are later dissected and imaged to quantify distribution of fluorescent nanoparticles within the suprachoroidal space.
View Article and Find Full Text PDFA 75-year-old man was treated for non-small cell lung cancer (NSCLC) (stage IIIb) with three-cycle chemotherapy (cisplatin and paclitaxel) for 3 weeks. No skin lesions were observed during the first and second chemotherapy cycles. After the third chemotherapy cycle, he developed slightly pruritic skin eruptions on the anterior chest.
View Article and Find Full Text PDFBackground/aims: The prevalence of hepatitis delta virus (HDV) infection has been estimated as being approximately 5% among global HBsAg carriers. The anti-delta positive rate in Koreans had been reported as being 0.85% in 1985.
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