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A drawback in the development of treatments that can reach the retina is the presence of barriers in the eye that restrain compounds from reaching the target. Intravitreal injections hold promise for retinal delivery, but the natural defenses in the vitreous can rapidly degrade or eliminate therapeutic molecules. Injectable hydrogel implants, which act as a reservoir, can allow for long-term drug delivery with a single injection into the eye, but still suffer due to the fast clearance of the released drugs when traversing the vitreous and random diffusion that leads to lower pharmaceutic efficacy. A combination with HA-covered nanoparticles, which can be released from the gel and more readily pass through the vitreous to increase the delivery of therapeutic agents to the retina, represents an advanced and elegant way to overcome some of the limitations in eye drug delivery. In this article, we developed hybrid PLGA-Dotap NPs that, due to their hyaluronic acid coating, can improve in vivo distribution throughout the vitreous and delivery to retinal cells. Moreover, a hydrogel implant was developed to act as a depot for the hybrid NPs to better control and slow their release. These results are a first step to improve the treatment of retinal diseases by protecting and transporting the therapeutic treatment across the vitreous and to improve treatment options by creating a depot system for long-term treatments. [ABSTRACT FROM AUTHOR]

In recent years, polyphenols have been extensively studied due to their antioxidant, anticancer, and anti-inflammatory properties. It has been shown that anthocyanins, flavonols, and flavan-3-ols play an important role in the prevention of bacterial infections, as well as vascular or skin diseases. Particularly, resveratrol, as a multi-potent agent, may prevent or mitigate the effects of oxidative stress. As the largest organ of the human body, skin is an extremely desirable target for the possible delivery of active substances. The transdermal route of administration of active compounds shows many advantages, including avoidance of gastrointestinal irritation and the first-pass effect. Moreover, it is non-invasive and can be self-administered. However, this delivery is limited, mainly due to the need to overpassing the stratum corneum, the possible decomposition of the substances in contact with the skin surface or in the deeper layers thereof. In addition, using resveratrol for topical and transdermal delivery faces the problems of its low solubility and poor stability. To overcome this, novel systems of delivery are being developed for the effective transport of resveratrol across the skin. Carriers in the micro and nano size were demonstrated to be more efficient for safe and faster topical and transdermal delivery of active substances. The present review aimed to discuss the role of resveratrol in the treatment of skin abnormalities with a special emphasis on technologies enhancing transdermal delivery of resveratrol. [ABSTRACT FROM AUTHOR]

Postprandial hyperglycemia, a so-called blood glucose spike, is associated with enhanced risks of diabetes mellitus (DM) and its complications. In this study, we attempted to design nanoparticles (NPs) of protamine zinc insulin (PZI) by the bead mill method, and prepare ophthalmic formulations based on the PZI-NPs with (nPZI/P) or without polyacrylic acid (nPZI). In addition, we investigated whether the instillation of the newly developed nPZI and nPZI/P can prevent postprandial hyperglycemia in a rabbit model involving the oral glucose tolerance test (OGTT). The particle size of PZI was decreased by the bead mill to a range for both nPZI and nPZI/P of 80–550 nm with no observable aggregation for 6 d. Neither nPZI nor nPZI/P caused any noticeable corneal toxicity. The plasma INS levels in rabbits instilled with nPZI were significantly higher than in rabbits instilled with INS suspensions (commercially available formulations, CA-INS), and the plasma INS levels were further enhanced with the amount of polyacrylic acid in the nPZI/P. In addition, the rapid rise in plasma glucose levels in OGTT-treated rabbits was prevented by a single instillation of nPZI/P, which was significantly more effective at attenuating postprandial hyperglycemia (blood glucose spike) in comparison with nPZI. In conclusion, we designed nPZI/P, and show that a single instillation before OGTT attenuates the rapid enhancement of plasma glucose levels. These findings suggest a better management strategy for the postprandial blood glucose spike, which is an important target of DM therapy. [ABSTRACT FROM AUTHOR]

A potent cell division cycle 7 (CDC7) kinase inhibitor, known as PHA-767491, has been described to reduce the transactive response DNA binding protein of 43 KDa (TDP-43) phosphorylation in vitro and in vivo, which is one of the main proteins found to aggregate and accumulate in the cytoplasm of motoneurons in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. However, the main drawback of this compound is its low permeability to the central nervous system (CNS), limiting its use for the treatment of neurological conditions. In this context, the use of drug delivery systems like nanocarriers has become an interesting approach to improve drug release to the CNS. In this study, we prepared and characterized biodegradable nanoparticles in order to encapsulate PHA-767491 and improve its permeability to the CNS. Our results demonstrate that poly (lactic-co-glycolic acid) (PLGA) nanoparticles with an average radius between 145 and 155 nm could be used to entrap PHA-767491 and enhance the permeability of this compound through the blood–brain barrier (BBB), becoming a promising candidate for the treatment of TDP-43 proteinopathies such as ALS. [ABSTRACT FROM AUTHOR]

The accumulation of amyloid β (Aβ) triggers a cascade of toxic events in Alzheimer's disease (AD). The KLVFF peptide can interfere with Aβ aggregation. However, the peptide suffers from poor bioavailability and the inability to cross the blood–brain barrier. In this work, we study the possibility of adopting nanomedicine to overcome KLVFF limits in biodistribution. We produced new engineered polymeric nanoparticles (NPs), and we evaluated the cellular toxicity of these NPs and validated that KVLFF peptides released by NPs show the same promising effects on AD pathology. Our results revealed the successful generation of KVLFF loaded NPs that, without significant effects on cell heath, are even more potent in reversing Aβ-induced pathologies compared to the free peptide. Therefore, NPs will significantly advance KVLFF treatment as a therapeutic option for AD. [ABSTRACT FROM AUTHOR]