Long-acting nanoparticle-loaded bilayer microneedles for protein delivery to the posterior segment of the eye
TL;DR: In this article, a model protein, ovalbumin (OVA)-encapsulated PLGA NPs were prepared and optimized using a water-in-oil-inwater (W/O/W) double emulsion method.
About: This article is published in European Journal of Pharmaceutics and Biopharmaceutics.The article was published on 2021-05-26. It has received 27 citations till now. The article focuses on the topics: Bilayer.
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TL;DR: In this article , the authors demonstrate the effectiveness of microneedle scleral patch in delivering the model molecule, triamcinolone acetonide, to the posterior segment of the eye.
14 citations
TL;DR: In this paper, the authors demonstrate the effectiveness of microneedle scleral patch in delivering the model molecule, triamcinolone acetonide, to the posterior segment of the eye.
14 citations
TL;DR: In this article , the authors developed a tip-loaded NES-nanosuspension (NES-NS)-loaded bilayer DMNs to deliver Nestorone intradermally for subsequent release.
14 citations
01 Jan 2022
TL;DR: In this article, different types of microneedle array patch (MAP)-based self-application technology bypasses many of the challenges associated with injectable routes by delivering the therapeutic materials directly into the intradermal space and allowing the release of the active ingredient in a sustained or controlled manner.
Abstract: The development of microneedle (MN)-assisted drug delivery technologies has been highly active for nearly two decades. The microneedle array patch (MAP)-based self-application technology bypasses many of the challenges associated with injectable routes by delivering the therapeutic materials directly into the intradermal space and allowing the release of the active ingredient in a sustained or controlled manner. Different types of biodegradable solid/dissolving MAP and nanoparticle-loaded/coated polymeric MAP or hollow MN have been envisioned for long-acting sustained delivery of therapeutic payloads, aiming for reducing the side effects and administration frequency to improve patient compliance. In this chapter, we covered the different types of MAPs that are loaded with different nano/biotherapeutics for long-acting delivery for a wide range of potential clinical applications. We have outlined the future development scenario for this long-acting MAP delivery system to achieve promising clinical benefits. Finally, it discusses the challenges to realize the full potential of long-acting sustained-release MNs in the clinic.
11 citations
TL;DR: This review summarizes the latest achievements in the field of obtaining microneedle ocular patches and discusses the most important advantages and drawbacks related to the unique anatomy and physiology of the eye.
Abstract: Eye diseases and injuries constitute a significant clinical problem worldwide. Safe and effective delivery of drugs to the eye is challenging mostly due to the presence of ocular barriers and clearance mechanisms. In everyday practice, the traditional eye drops, gels and ointments are most often used. Unfortunately, they are usually not well tolerated by patients due to the need for frequent use as well as the discomfort during application. Therefore, novel drug delivery systems with improved biopharmaceutical properties are a subject of ongoing scientific investigations. Due to the developments in microtechnology, in recent years, there has been a remarkable advance in the development of microneedle-based systems as an alternative, non-invasive form for administering drugs to the eye. This review summarizes the latest achievements in the field of obtaining microneedle ocular patches. In the manuscript, the most important manufacturing technologies, microneedle classification, and the research studies related to ophthalmic application of microneedles are presented. Finally, the most important advantages and drawbacks, as well as potential challenges related to the unique anatomy and physiology of the eye are summarized and discussed.
7 citations
References
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TL;DR: A pH gradient is shown, with the most acidic environment at the center of the spheres and higher pH near the edges, which is characteristic of diffusion-controlled release of the acidicdegradation products.
Abstract: Purpose In the past decade, biodegradable polymers have becomethe materials of choice for a variety of biomaterials applications Inparticular, poly(lactic-co-glycolic acid) (PLGA) microspheres havebeen extensively studied for controlled-release drug delivery However,degradation of the polymer generates acidic monomers, andacidification of the inner polymer environment is a central issue in thedevelopment of these devices for drug delivery
Methods To quantitatively determine the intrapolymer acidity, weentrapped pH-sensitive fluorescent dyes (conjugated to 10,000 Dadextrans) within the microspheres and imaged them with confocalfluorescence microscopy The technique allows visualization of thespatial and temporal distribution of pH within the degradingmicrospheres (1)
Results Our experiments show the formation of a very acidicenvironment within the particles with the minimum pH as low as 15
Conclusions The images show a pH gradient, with the most acidicenvironment at the center of the spheres and higher pH near the edges,which is characteristic of diffusion-controlled release of the acidicdegradation products
755 citations
TL;DR: The use of various stabilization approaches has rendered some success in increasing protein stability, but, still, full preservation of the native protein structure remains a major challenge in the formulation of protein-loaded PLGA microparticles.
Abstract: In this review the current knowledge of protein degradation during preparation, storage and release from poly(lactic-co-glycolic acid) (PLGA) microparticles is described, as well as stabilization approaches. Although we have focussed on PLGA microparticles, the degradation processes and mechanisms described here are valid for many other polymeric release systems. Optimized process conditions as well as stabilizing excipients need to be used to counteract several stress factors that compromise the integrity of protein structure during preparation, storage, and release. The use of various stabilization approaches has rendered some success in increasing protein stability, but, still, full preservation of the native protein structure remains a major challenge in the formulation of protein-loaded PLGA microparticles.
721 citations
TL;DR: Clinical micrographs reveal that the polyvinylalcohol (PVA as an emulsifier) concentration in the external water phase strongly influences drug distribution within microspheres and release profiles, and the presence of PVA in the internal water phase enhances the stabilization of inner water droplets against coalescence.
706 citations
TL;DR: To neutralize the acids liberated by the biodegradable lactic/glycolic acid-based polyester, the authors coincorporated into the polymer an antacid, Mg(OH)2, which increased microclimate pH and prevented BSA structural losses and aggregation for over one month.
Abstract: Controlled release from biodegradable polymers is a novel approach to replace daily painful injections of protein drugs A major obstacle to development of these polymers is the need to retain the structure and biological activity of encapsulated proteins during months of incubation under physiological conditions We encapsulated bovine serum albumin (BSA) in injectable poly(DL-lactide- co-glycolide) (PLGA) 50/50 cylindrical implants and determined the mechanism of BSA instability Simulations of the polymer microclimate revealed that moisture and acidic pH (<3) triggered unfolding of encapsulated BSA, resulting in peptide bond hydrolysis and noncovalent aggregation To neutralize the acids liberated by the biodegradable lactic/glycolic acid-based polyester, we coincorporated into the polymer an antacid, Mg(OH)2, which increased microclimate pH and prevented BSA structural losses and aggregation for over one month We successfully applied this stabilization approach in both cylinder- and microsphere-injectable configurations and for delivery of angiogenic basic fibroblast growth factor and bone-regenerating bone morphogenetic protein-2
637 citations
Journal Article•
TL;DR: Transscleral delivery of immunoglobulins and other large compounds to the choroid and retina may be feasible and large molecules, such as IgG, diffuse across sclera in a manner consistent with porous diffusion through a fiber matrix.
Abstract: Purpose To determine the in vitro permeability of the sclera to high molecular weight compounds and the relationship between scleral permeability and molecular size. Methods Fresh rabbit sclera was mounted in a two-chamber diffusion apparatus, and its permeability to sodium fluorescein, fluorescein isothiocyanate (FITC)-conjugated bovine serum albumin, FITC-IgG, and FITC dextrans ranging in molecular weight from 4 to 150 kDa was determined by fluorescence spectrophotometry. Electron microscopy was used to assess the impact of the experimental design on scleral ultrastructural integrity. The effect of the diffusion apparatus on scleral hydration was examined. Rabbit scleral permeability was compared with previously reported data for human and bovine sclera. Results Scleral permeability decreased with increasing molecular weight and molecular radius, consistent with previous human and bovine data. Molecular radius was a better predictor of scleral permeability than molecular weight. The sclera was more permeable to globular proteins than to linear dextrans of similar molecular weight. The experimental apparatus did not alter scleral ultrastructure. Permeability of rabbit sclera was similar to human sclera but greater than bovine sclera. Conclusions Large molecules, such as IgG, diffuse across sclera in a manner consistent with porous diffusion through a fiber matrix. Transscleral delivery of immunoglobulins and other large compounds to the choroid and retina may be feasible.
373 citations