Nanofiber-coated, tacrolimus-eluting sutures inhibit post-operative neointimal hyperplasia in rats.

Post-operative complications of vascular anastomosis procedures remain a significant clinical challenge and health burden globally. Each year, millions of anastomosis procedures connect arteries and/or veins in vascular bypass, vascular access, organ transplant, and reconstructive surgeries, generally via suturing. Dysfunction of these anastomoses, primarily due to neointimal hyperplasia and the resulting narrowing of the vessel lumen, results in failure rates of up to 50% and billions of dollars in costs to the healthcare system. Non-absorbable sutures are the gold standard for vessel anastomosis; however, damage from the surgical procedure and closure itself causes an inflammatory cascade that leads to neointimal hyperplasia at the anastomosis site. Here, we demonstrate the development of a novel, scalable manufacturing system for fabrication of high strength sutures with nanofiber-based coatings composed of generally regarded as safe (GRAS) polymers and either sirolimus, tacrolimus, everolimus, or pimecrolimus. These sutures provided sufficient tensile strength for maintenance of the vascular anastomosis and sustained drug delivery at the site of the anastomosis. Tacrolimus-eluting sutures provided a significant reduction in neointimal hyperplasia in rats over a period of 14 days with similar vessel endothelialization in comparison to conventional nylon sutures. In contrast, systemically delivered tacrolimus caused significant weight loss and mortality due to toxicity. Thus, drug-eluting sutures provide a promising platform to improve the outcomes of vascular interventions without modifying the clinical workflow and without the risks associated with systemic drug delivery.

An ion-paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection.

There are numerous barriers to achieving effective intraocular drug administration, including the mucus layer protecting the ocular surface. For this reason, antibiotic eye drops must be used multiple times per day to prevent and treat ocular infections. Frequent eye drop use is inconvenient for patients, and lack of adherence to prescribed dosing regimens limits treatment efficacy and contributes to antibiotic resistance. Here, we describe an ion-pairing approach used to create an insoluble moxifloxacin-pamoate (MOX-PAM) complex for formulation into mucus-penetrating nanosuspension eye drops (MOX-PAM NS). The MOX-PAM NS provided a significant increase in ocular drug absorption, as measured by the area under the curve in cornea tissue and aqueous humor, compared to Vigamox in healthy rats. Prophylactic and treatment efficacy were evaluated in a rat model of ocular Staphylococcus aureus infection. A single drop of MOX-PAM NS was more effective than Vigamox, and completely prevented infection. Once a day dosing with MOX-PAM NS was similar, if not more effective, than three times a day dosing with Vigamox for treating S. aureus infection. The MOX-PAM NS provided increased intraocular antibiotic absorption and improved prevention and treatment of ocular keratitis, and the formulation approach is highly translational and clinically relevant.

Ultra-thin, high strength, antibiotic-eluting sutures for prevention of ophthalmic infection.

Sutures are applied almost universally at the site of trauma or surgery, making them an ideal platform to modulate the local, postoperative biological response, and improve surgical outcomes. To date, the only globally marketed drug-eluting sutures are coated with triclosan for antibacterial application in general surgery. Loading drug directly into the suture rather than coating the surface offers the potential to provide drug delivery functionality to microsurgical sutures and achieve sustained drug delivery without increasing suture thickness. However, conventional methods for drug incorporation directly into the suture adversely affect breaking strength. Thus, there are no market offerings for drug-eluting sutures, drug-coated, or otherwise, in ophthalmology, where very thin sutures are required. Sutures themselves help facilitate bacterial infection, and antibiotic eye drops are commonly prescribed to prevent infection after ocular surgeries. An antibiotic-eluting suture may prevent bacterial colonization of sutures and preclude patient compliance issues with eye drops. We report twisting of hundreds of individual drug-loaded, electrospun nanofibers into a single, ultra-thin, multifilament suture capable of meeting both size and strength requirements for microsurgical ocular procedures. Nanofiber-based polycaprolactone sutures demonstrated no loss in strength with loading of 8% levofloxacin, unlike monofilament sutures which lost more than 50% strength. Moreover, nanofiber-based sutures retained strength with loading of a broad range of drugs, provided antibiotic delivery for 30 days in rat eyes, and prevented ocular infection in a rat model of bacterial keratitis.

Nano-structured glaucoma drainage implant safely and significantly reduces intraocular pressure in rabbits via post-operative outflow modulation.

Glaucoma is a leading cause of irreversible vision loss predicted to affect more than 100 million people by 2040. Intraocular pressure (IOP) reduction prevents development of glaucoma and vision loss from glaucoma. Glaucoma surgeries reduce IOP by facilitating aqueous humor outflow through a vent fashioned from the wall of the eye (trabeculectomy) or a glaucoma drainage implant (GDI), but surgeries lose efficacy overtime, and the five-year failure rates for trabeculectomy and tube shunts are 25-45%. The majority of surgical failures occur due to fibrosis around the vent. Alternatively, surgical procedures can shunt aqueous humor too well, leading to hypotony. Electrospinning is an appealing manufacturing platform for GDIs, as it allows for incorporation of biocompatible polymers into nano- or micro-fibers that can be configured into devices of myriad combinations of dimensions and conformations. Here, small-lumen, nano-structured glaucoma shunts were manufactured with or without a degradable inner core designed to modulate aqueous humor outflow to provide immediate IOP reduction, prevent post-operative hypotony, and potentially offer significant, long-term IOP reduction. Nano-structured shunts were durable, leak-proof, and demonstrated biocompatibility and patency in rabbit eyes. Importantly, both designs prevented hypotony and significantly reduced IOP for 27 days in normotensive rabbits, demonstrating potential for clinical utility.

Inner retinal vasculopathy in Zika virus disease.

PURPOSE: Zika virus infection is associated with vision-threatening ocular complications including uveitis and outer retinopathy. The aim of this report is to describe a case of an adult patient with serologically confirmed Zika infection who presented with retinal vascular abnormalities that coincided with systemic post-viral neurological manifestations of the disease. OBSERVATIONS: A 34-year-old white female presented with symptoms of peripheral neuropathy following serologically confirmed Zika virus infection that was acquired in Puerto Rico four months prior to presentation. Ocular evaluation revealed perifoveal microaneurysms which were not associated with visual symptoms. CONCLUSIONS AND IMPORTANCE: These data potentially expand the phenotypic spectrum of Zika virus retinopathy. In addition to outer retinal abnormalities which are well-described in infants and adults, inner retinal vascular abnormalities may also occur and may be temporally associated with post-viral neurological sequelae of Zika virus infection. Clinicians should be aware of potential retinal involvement in affected patients who present with neurological symptoms after recovery from acute Zika virus infection.

Ocular effects of Zika virus-a review.

Zika virus was considered an innocent pathogen while restricted to the African and Asian population; however, after reaching the Americas in March 2015, it became a global threat. Despite usually causing mild or no symptoms in infected adults, Zika virus displays a different behavior toward fetuses. When infected during gestation, fetuses have their immature neural cells killed by the virus and consequently have devastating findings at birth. In the past year the drastic effects of Zika virus infection in newborns include neurological, ophthalmological, audiological, and skeletal abnormalities. These findings represent a new entity called congenital Zika syndrome. We summarize the ocular findings of congenital Zika Syndrome, as well as the current understanding of the illness, systemic manifestations, laboratory investigation, differential diagnosis, prophylaxis, and treatment for this disorder.

Development of Absorbable, Antibiotic-Eluting Sutures for Ophthalmic Surgery.

PURPOSE: To develop and evaluate an antibiotic-eluting suture for ophthalmic surgery. METHODS: Wet electrospinning was used to manufacture sutures composed of poly(L-lactide), polyethylene glycol (PEG), and levofloxacin. Size, morphology, and mechanical strength were evaluated via scanning electron microscopy and tensile strength, respectively. In vitro drug release was quantified using high performance liquid chromatography. In vitro suture activity against Staphylococcus epidermidis was investigated through bacterial inhibition studies. Biocompatibility was determined via histological analysis of tissue sections surrounding sutures implanted into Sprague-Dawley rat corneas. RESULTS: Sutures manufactured via wet electrospinning were 45.1 ± 7.7 µm in diameter and 0.099 ± 0.007 newtons (N) in breaking strength. The antibiotic release profile demonstrated a burst followed by sustained release for greater than 60 days. Increasing PEG in the polymer formulation, from 1% to 4% by weight, improved drug release without negatively affecting tensile strength. Sutures maintained a bacterial zone of inhibition for at least 1 week in vitro and elicited an in vivo tissue reaction comparable to a nylon suture. CONCLUSIONS: There is a need for local, postoperative delivery of antibiotics following ophthalmic procedures. Wet electrospinning provides a suitable platform for the development of sutures that meet size requirements for ophthalmic surgery and are capable of sustained drug release; however, tensile strength must be improved prior to clinical use. TRANSLATIONAL RELEVANCE: No antibiotic-eluting suture exists for ophthalmic surgery. A biocompatible, high strength suture capable of sustained antibiotic release could prevent ocular infection and preclude compliance issues with topical eye drops.