Pharmacokinetic Investigation of Quetiapine Transport across Blood–Brain Barrier Mediated by Lipid Core Nanocapsules Using Brain Microdialysis in Rats

Carreño, Fernando; Paese, Karina; Silva, Carolina Miranda; Guterres, Sílvia Stanisçuaski; Costa, Teresa Dalla

doi:10.1021/acs.molpharmaceut.5b00875

Cited by 32 publications

(32 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5 For drugs with active influx (K p,uu > 1), liposomal encapsulation does not seem to be a good solution if the purpose is to further increase the brain uptake, although examples are still sparse. 8 Therefore, it is of crucial importance to be aware of the basic BBB transport features of the drug intended to be encapsulated.…”

Section: ■ Discussionmentioning

confidence: 99%

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

Gaillard

Rip³

et al. 2018

Mol. Pharmaceutics

View full text Add to dashboard Cite

License: Article 25fa pilot End User Agreement This publication is distributed under the terms of Article 25fa of the Dutch Copyright Act (Auteurswet) with explicit consent by the author. Dutch law entitles the maker of a short scientific work funded either wholly or partially by Dutch public funds to make that work publicly available for no consideration following a reasonable period of time after the work was first published, provided that clear reference is made to the source of the first publication of the work. This publication is distributed under The Association of Universities in the Netherlands (VSNU) 'Article 25fa implementation' pilot project. In this pilot research outputs of researchers employed by Dutch Universities that comply with the legal requirements of Article 25fa of the Dutch Copyright Act are distributed online and free of cost or other barriers in institutional repositories. Research outputs are distributed six months after their first online publication in the original published version and with proper attribution to the source of the original publication. You are permitted to download and use the publication for personal purposes. All rights remain with the author(s) and/or copyrights owner(s) of this work. Any use of the publication other than authorised under this licence or copyright law is prohibited. If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons.

show abstract

Section: ■ Discussionmentioning

confidence: 99%

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

Gaillard

Rip³

et al. 2018

Mol. Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…CMA 12 probes for brain D (3-mm polyarylethersulfone membrane and 20-kDa cutoff; CMA Microdialysis, Sweden) were used. Artificial cerebrospinal fluid (ACF; 145 mM NaCl, 2.7 mM KCl, 1.2 mM CaCl 2 , 1 mM MgCl 2 [pH 7.4]) was used, prepared as described previously (36).…”

Section: Microorganismsmentioning

confidence: 99%

Influence of Experimental Cryptococcal Meningitis in Wistar Rats on Voriconazole Brain Penetration Assessed by Microdialysis

Alves

Staudt

Silva

et al. 2017

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

To make advances in the treatment of cryptococcal meningitis, it is crucial to know a given drug's free fraction that reaches the biophase. In the present study, we applied microdialysis (D) as a tool to determine the free levels reached by voriconazole (VRC) in the brains of healthy and Cryptococcus neoformans-infected rats. The infection was induced by the intravenous (i.v.) administration of 1 ϫ 10 5 CFU of yeast. The dose administered was 5 mg/kg (of body weight) of VRC, given i.v. Plasma and microdialysate samples were analyzed by liquid chromatographytandem mass spectrometry (LC-MS/MS) and LC-UV methods. The free brain/free plasma ratio (fT) and population pharmacokinetic (popPK) analyses were performed to evaluate the impact of infection on PK parameters of the drug. The brain penetration ratio showed an increase on brain exposure in infected animals (fT healthy ϭ 0.85 versus fT infected ϭ 1.86). The structural PK model with two compartments and Michaelis-Menten (MM) elimination describes the VRC concentration-time profile in plasma and tissue simultaneously. The covariate infection was included in volume of distribution in the peripheral compartment in healthy animals (V 2 ) and maximum rate of metabolism (V M ). The levels reached in infected tissues were higher than the values described for MIC of VRC for Cryptococccus neoformans (0.03 to 0.5 g ml Ϫ1 ), indicating its great potential to treat meningitis associated with C. neoformans.

show abstract

“…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%

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

Hammarlund‐Udenaes

2020

Mol. Pharmaceutics

View full text Add to dashboard Cite

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.

show abstract

Pharmacokinetic Investigation of Quetiapine Transport across Blood–Brain Barrier Mediated by Lipid Core Nanocapsules Using Brain Microdialysis in Rats

Cited by 32 publications

References 34 publications

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

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

Influence of Experimental Cryptococcal Meningitis in Wistar Rats on Voriconazole Brain Penetration Assessed by Microdialysis

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

Contact Info

Product

Resources

About