In Vivo Quantitative Understanding of PEGylated Liposome’s Influence on Brain Delivery of Diphenhydramine

Hu, Yang; Gaillard, Pieter J.; Rip, Jaap; Lange, Elizabeth C. M. de; Hammarlund‐Udenaes, Margareta

doi:10.1021/acs.molpharmaceut.8b00611

Cited by 25 publications

(28 citation statements)

References 18 publications

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“…Liposomes are recognized as promising agents for drug delivery due to their biocompatibility and ability to cross physiological barriers [11,12]. Liposomes have been clinically approved for various medical applications including anticancer treatment, owing to their high therapeutic efficacy and low cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo

et al. 2019

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The methylated analogue of the polyphenol resveratrol (RV), 2,3′,4,5′-tetramethoxystilbene (TMS) displays potent antioxidant properties and is an effective cytochrome P450 (CYP) 1B1 inhibitor. The bioavailability of TMS is low. Therefore, the use of liposomes for the encapsulation of TMS is a promising delivery modality for enhanced uptake into tissues. We examined the effect of delivery of TMS in liposomes on the restoration of vasodilator responses of isolated aortic vessels after acute tension elevation ex vivo. Aortic vessels from young male Wistar rats were isolated, and endothelial-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) responses assessed. Acute tension elevation (1 h) significantly reduced ACh dilator responses, which were restored following incubation with superoxide dismutase or apocynin (an NADPH oxidase inhibitor). Incubation with TMS-loaded liposomes (mean diameter 157 ± 6 nm; PDI 0.097) significantly improved the attenuated dilator responses following tension elevation, which was sustained over a longer period (4 h) when compared to TMS solution. Endothelial denudation or co-incubation with L-NNA (Nω-nitro-l-arginine; nitric oxide synthase inhibitor) resulted in loss of dilator function. Our findings suggest that TMS-loaded liposomes can restore attenuated endothelial-dependent dilator responses induced by an oxidative environment by reducing NADPH-oxidase-derived ROS and potentiating the release of the vasodilator nitric oxide. TMS-loaded liposomes may be a promising therapeutic strategy to restore vasodilator function in vascular disease.

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Section: Introductionmentioning

confidence: 99%

Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo

et al. 2019

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“…In comparison, a hydrogenated soy phosphatidylcholine (HSPC) displayed poorer permeation into the parenchyma. Confirming once again the importance of the starting material [ 140 ].…”

Section: Brain Delivery Of Nanoparticles With Bbb-shuttlesmentioning

confidence: 78%

Peptide Mediated Brain Delivery of Nano- and Submicroparticles: A Synergistic Approach

McCully

Sánchez‐Navarro

Teixidó

et al. 2018

CPD

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The brain is a complex, regulated organ with a highly controlled access mechanism: The Blood-Brain Barrier (BBB). The selectivity of this barrier is a double-edged sword, being both its greatest strength and weakness. This weakness is evident when trying to target therapeutics against diseases within the brain. Diseases such as metastatic brain cancer have extremely poor prognosis due to the poor permeability of many therapeutics across the BBB. Peptides can be designed to target BBB receptors and gain access to the brain by transcytosis. These peptides (known as BBB-shuttles) can carry compounds, usually excluded from the brain, across the BBB. BBB-shuttles are limited by poor loading of therapeutics and degradation of the peptide and cargo. Likewise, nano- submicro- and microparticles can be fine-tuned to limit their degradation and with high loading of therapeutics. However, most nano- and microparticles’ core materials completely lack efficient targeting, with a few selected materials able to cross the BBB passively. Combining the selectivity of peptides with the high loading potential of nano-, microparticles offers an exciting strategy to develop novel, targeted therapeutics towards many brain disorders and diseases. Nevertheless, at present the field is diverse, in both scope and nomenclature, often with competing or contradictory names. In this review, we will try to address some of these issues and evaluate the current state of peptide mediated nano,-microparticle transport to the brain, analyzing delivery vehicle type and peptide design, the two key components that must act synergistically for optimal therapeutic impact.

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“…This is exemplified by two recent studies showing that encapsulation in PEGylated liposomes and lipid core nanocapsules significantly decreased the K p,uu,brain of diphenhydramine and quetiapine. 11 , 35 …”

Section: What Factors Could Impact the Therapeutic Success Of Nanodelmentioning

confidence: 99%

“… 10 , 12 Furthermore, when encapsulating in PEG-EYPC liposomes, diphenhydramine was released much faster compared to methotrexate based on both in vitro and in vivo findings ( Figure 2 ). 11 , 12 In a simulation study, the in vivo drug release was found to be strongly associated with therapeutic performance due to its influence on peripheral side effects. 34 …”

Section: What Factors Could Impact the Therapeutic Success Of Nanodelmentioning

confidence: 99%

Perspectives on Nanodelivery to the Brain: Prerequisites for Successful Brain Treatment

Hammarlund‐Udenaes

2020

Mol. Pharmaceutics

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Nanocarriers (NCs) are promising tools to improve drug delivery across the blood–brain barrier (BBB) for more effective treatment of brain disorders, although there is a scarcity of clinical translation of brain-directed NCs. In order to drive the development of brain-oriented NCs toward clinical success, it is essential to understand the prerequisites for nanodelivery to be successful in brain treatment. In this Perspective, we present how pharmacokinetic/pharmacodynamic (PK/PD), formulation and nanotoxicity factors impact the therapeutic success of brain-specific nanodelivery. Properties including high loading efficiency, slow in vivo drug release, long systemic circulation, an increase in unbound brain-to-plasma concentration/exposure ratio ( K p,uu,brain ), high drug potency, and minimal nanotoxicity are prerequisites that should preferably be combined to maximize the therapeutic potential of a brain-targeted NC. The PK of brain-directed NCs needs to be evaluated in a more therapeutically relevant manner, focusing on the released, unbound drug. It is more crucial to increase the K p,uu,brain than to improve the ability of the NC to cross the BBB in its intact form. Brain-targeted NCs, which are mostly developed for treating brain tumors, including metastases, should aim to enhance drug delivery not just to tumor regions with disrupted BBB, but equally important to regions with intact BBB where the drugs themselves have problems reaching. This article provides critical insights into how a brain-targeted nanoformulation needs to be designed and optimized to achieve therapeutic success in the brain.

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In Vivo Quantitative Understanding of PEGylated Liposome’s Influence on Brain Delivery of Diphenhydramine

Cited by 25 publications

References 18 publications

Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo

Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo

Peptide Mediated Brain Delivery of Nano- and Submicroparticles: A Synergistic Approach

Perspectives on Nanodelivery to the Brain: Prerequisites for Successful Brain Treatment

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