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Pharmaceutics
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Strategies to Enhance Drug Permeability across Biological Barriers
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Strategies to Enhance Drug Permeability across Biological Barriers

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (10 July 2022) | Viewed by 50692

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Jingyuan Wen

E-Mail Website
Guest Editor
School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1010, New Zealand
Interests: drug delivery system; nanoparticles; polymer–drug conjugates; tumor targeting; permeability enhancement
Prof. Dr. Yuan Huang

E-Mail Website
Guest Editor
West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Interests: oral, topical, and transdermal delivery; nanoparticle; microemulsion; oral dosage forms design

Special Issue Information

Dear Colleagues,

Delivery of therapeutic drugs to desired sites, and at required rates/extents, is limited by numerous biological barriers in the body, including the intestinal epithelium membrane, blood–brain barrier (BBB), and skin barrier. Drug permeability across the intestinal membrane is mainly limited by the physical barriers presented by the mucous layer, the epithelial membrane, and the tight junctions and enzymatic barrier (especially for unstable compounds). Similarly, drug permeability across the BBB is limited by the brain’s capillary endothelial cells, which are characterized by continuous tight junctions. Almost 100% of macromolecular drugs and 98% of small lipophilic drugs are unable to cross the BBB. Likewise, drug permeability across the skin is limited by the formidable barrier of stratum corneum and the tight junctions.

A wide range of approaches and technologies have been investigated to overcome these biological barriers. Among the different approaches, advanced and innovative drug delivery systems, especially targeting-based strategies, have garnered tremendous attention in recent years. 

This Special Issue aims to highlight recent advancements in technologies to overcome these barriers and improve drug permeability. We welcome articles providing new insights on all aspects of enhancement of drug penetration across the biological barriers.

Dr. Jingyuan Wen
Prof. Dr. Yuan Huang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • formulation strategy
  • blood–brain barrier
  • skin barrier
  • transdermal delivery
  • topical delivery
  • oral delivery
  • intestinal epithelial barrier
  • drug permeability

Published Papers (13 papers)

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Editorial

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3 pages, 166 KiB  
Editorial
Strategies to Enhance Drug Permeability across Biological Barriers—A Summary of This Important Special Issue
by Jingyuan Wen and Yuan Huang
Pharmaceutics 2023, 15(4), 1189; https://doi.org/10.3390/pharmaceutics15041189 - 8 Apr 2023
Cited by 3 | Viewed by 1313
Abstract
This Special Issue, “Strategies to Enhance Drug Permeability across Biological Barriers”, is hosted by Pharmaceutics and highlights the recent technological advancements for overcoming biological barriers and improving drug permeability and absorption [...] Full article
(This article belongs to the Special Issue Strategies to Enhance Drug Permeability across Biological Barriers)

Research

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16 pages, 4463 KiB  
Article
Mitochondria-Targeted Delivery of Camptothecin Based on HPMA Copolymer for Metastasis Suppression
by Xiaoli Yi, Yue Yan, Xinran Shen, Lian Li and Yuan Huang
Pharmaceutics 2022, 14(8), 1534; https://doi.org/10.3390/pharmaceutics14081534 - 23 Jul 2022
Cited by 4 | Viewed by 1605
Abstract
Poor anti-metastasis effects and side-effects remain a challenge for the clinical application of camptothecin (CPT). Mitochondria can be a promising target for the treatment of metastatic tumors due to their vital roles in providing energy supply, upregulating pro-metastatic factors, and controlling cell-death signaling. [...] Read more.
Poor anti-metastasis effects and side-effects remain a challenge for the clinical application of camptothecin (CPT). Mitochondria can be a promising target for the treatment of metastatic tumors due to their vital roles in providing energy supply, upregulating pro-metastatic factors, and controlling cell-death signaling. Thus, selectively delivering CPT to mitochondria appears to be a feasible way of improving the anti-metastasis effect and reducing adverse effects. Here, we established a 2-(dimethylamino) ethyl methacrylate (DEA)-modified N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer–CPT conjugate (P-DEA-CPT) to mediate the mitochondrial accumulation of CPT. The mitochondria-targeted P-DEA-CPT could overcome multiple barriers by quickly internalizing into 4T1 cells, then escaping from lysosome, and sufficiently accumulating in mitochondria. Subsequently, P-DEA-CPT greatly damaged mitochondrial function, leading to the reactive oxide species (ROS) elevation, energy depletion, apoptosis amplification, and tumor metastasis suppression. Consequently, P-DEA-CPT successfully inhibited both primary tumor growth and distant metastasis in vivo. Furthermore, our studies revealed that the mechanism underlying the anti-metastasis capacity of P-DEA-CPT was partially via downregulation of various pro-metastatic proteins, such as hypoxia induction factor-1α (HIF-1α), matrix metalloproteinases-2 (MMP-2), and vascular endothelial growth factor (VEGF). This study provided the proof of concept that escorting CPT to mitochondria via a mitochondrial targeting strategy could be a promising approach for anti-metastasis treatment. Full article
(This article belongs to the Special Issue Strategies to Enhance Drug Permeability across Biological Barriers)
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14 pages, 4740 KiB  
Article
Evaluation of CTB-sLip for Targeting Lung Metastasis of Colorectal Cancer
by Xiaoying Zhang, Wenjing Tang, Haoyu Wen, Ercan Wu, Tianhao Ding, Jie Gu, Zhongwei Lv and Changyou Zhan
Pharmaceutics 2022, 14(4), 868; https://doi.org/10.3390/pharmaceutics14040868 - 15 Apr 2022
Cited by 4 | Viewed by 2229
Abstract
Lung metastasis of colorectal cancer is common in the clinic; however, precise targeting for the diagnosis and therapy purposes of those lung metastases remains challenging. Herein, cholera toxin subunit b (CTB) protein was chemically conjugated on the surface of PEGylated liposomes (CTB-sLip). Both [...] Read more.
Lung metastasis of colorectal cancer is common in the clinic; however, precise targeting for the diagnosis and therapy purposes of those lung metastases remains challenging. Herein, cholera toxin subunit b (CTB) protein was chemically conjugated on the surface of PEGylated liposomes (CTB-sLip). Both human-derived colorectal cancer cell lines, HCT116 and HT-29, demonstrated high binding affinity and cellular uptake with CTB-sLip. In vivo, CTB-sLip exhibited elevated targeting capability to the lung metastasis of colorectal cancer in the model nude mice in comparison to PEGylated liposomes (sLip) without CTB modification. CTB conjugation induced ignorable effects on the interaction between liposomes and plasma proteins but significantly enhanced the uptake of liposomes by numerous blood cells and splenic cells, leading to relatively rapid blood clearance in BALB/c mice. Even though repeated injections of CTB-sLip induced the production of anti-CTB antibodies, our results suggested CTB-sLip as promising nanocarriers for the diagnosis of lung metastasis of colorectal cancer. Full article
(This article belongs to the Special Issue Strategies to Enhance Drug Permeability across Biological Barriers)
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25 pages, 3455 KiB  
Article
Niosomal Nanocarriers for Enhanced Dermal Delivery of Epigallocatechin Gallate for Protection against Oxidative Stress of the Skin
by Danhui Li, Nataly Martini, Zimei Wu, Shuo Chen, James Robert Falconer, Michelle Locke, Zhiwen Zhang and Jingyuan Wen
Pharmaceutics 2022, 14(4), 726; https://doi.org/10.3390/pharmaceutics14040726 - 28 Mar 2022
Cited by 25 | Viewed by 2832
Abstract
Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highest biological activities. This study aims to develop and statistically optimise an EGCG-loaded niosomal system to overcome the cutaneous barriers and provide an antioxidant effect. EGCG-niosomes were prepared by [...] Read more.
Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highest biological activities. This study aims to develop and statistically optimise an EGCG-loaded niosomal system to overcome the cutaneous barriers and provide an antioxidant effect. EGCG-niosomes were prepared by thin film hydration method and statistically optimised. The niosomes were characterised for size, zeta potential, morphology and entrapment efficiency. Ex vivo permeation and deposition studies were conducted using full-thickness human skin. Cell viability, lipid peroxidation, antioxidant enzyme activities after UVA-irradiation and cellular uptake were determined. The optimised niosomes were spherical and had a relatively uniform size of 235.4 ± 15.64 nm, with a zeta potential of −45.2 ± 0.03 mV and an EE of 53.05 ± 4.46%. The niosomes effectively prolonged drug release and demonstrated much greater skin penetration and deposition than free EGCG. They also increased cell survival after UVA-irradiation, reduced lipid peroxidation, and increased the antioxidant enzymes’ activities in human dermal fibroblasts (Fbs) compared to free EGCG. Finally, the uptake of niosomes was via energy-dependent endocytosis. The optimised niosomes have the potential to be used as a dermal carrier for antioxidants and other therapeutic compounds in the pharmaceutical and cosmetic industries. Full article
(This article belongs to the Special Issue Strategies to Enhance Drug Permeability across Biological Barriers)
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Review

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25 pages, 3378 KiB  
Review
Nanosystems, Drug Molecule Functionalization and Intranasal Delivery: An Update on the Most Promising Strategies for Increasing the Therapeutic Efficacy of Antidepressant and Anxiolytic Drugs
by Jéssica L. Antunes, Joana Amado, Francisco Veiga, Ana Cláudia Paiva-Santos and Patrícia C. Pires
Pharmaceutics 2023, 15(3), 998; https://doi.org/10.3390/pharmaceutics15030998 - 20 Mar 2023
Cited by 5 | Viewed by 2377
Abstract
Depression and anxiety are high incidence and debilitating psychiatric disorders, usually treated by antidepressant or anxiolytic drug administration, respectively. Nevertheless, treatment is usually given through the oral route, but the low permeability of the blood–brain barrier reduces the amount of drug that will [...] Read more.
Depression and anxiety are high incidence and debilitating psychiatric disorders, usually treated by antidepressant or anxiolytic drug administration, respectively. Nevertheless, treatment is usually given through the oral route, but the low permeability of the blood–brain barrier reduces the amount of drug that will be able to reach it, thus consequently reducing the therapeutic efficacy. Which is why it is imperative to find new solutions to make these treatments more effective, safer, and faster. To overcome this obstacle, three main strategies have been used to improve brain drug targeting: the intranasal route of administration, which allows the drug to be directly transported to the brain by neuronal pathways, bypassing the blood–brain barrier and avoiding the hepatic and gastrointestinal metabolism; the use of nanosystems for drug encapsulation, including polymeric and lipidic nanoparticles, nanometric emulsions, and nanogels; and drug molecule functionalization by ligand attachment, such as peptides and polymers. Pharmacokinetic and pharmacodynamic in vivo studies’ results have shown that intranasal administration can be more efficient in brain targeting than other administration routes, and that the use of nanoformulations and drug functionalization can be quite advantageous in increasing brain–drug bioavailability. These strategies could be the key to future improved therapies for depressive and anxiety disorders. Full article
(This article belongs to the Special Issue Strategies to Enhance Drug Permeability across Biological Barriers)
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21 pages, 2675 KiB  
Review
Dissolution and Absorption of Inhaled Drug Particles in the Lungs
by Basanth Babu Eedara, Rakesh Bastola and Shyamal C. Das
Pharmaceutics 2022, 14(12), 2667; https://doi.org/10.3390/pharmaceutics14122667 - 30 Nov 2022
Cited by 8 | Viewed by 3604
Abstract
Dry powder inhalation therapy has been effective in treating localized lung diseases such asthma, chronic obstructive pulmonary diseases (COPD), cystic fibrosis and lung infections. In vitro characterization of dry powder formulations includes the determination of physicochemical nature and aerosol performance of powder particles. [...] Read more.
Dry powder inhalation therapy has been effective in treating localized lung diseases such asthma, chronic obstructive pulmonary diseases (COPD), cystic fibrosis and lung infections. In vitro characterization of dry powder formulations includes the determination of physicochemical nature and aerosol performance of powder particles. The relationship between particle properties (size, shape, surface morphology, porosity, solid state nature, and surface hydrophobicity) and aerosol performance of an inhalable dry powder formulation has been well established. However, unlike oral formulations, there is no standard dissolution method for evaluating the dissolution behavior of the inhalable dry powder particles in the lungs. This review focuses on various dissolution systems and absorption models, which have been developed to evaluate dry powder formulations. It covers a summary of airway epithelium, hurdles to developing an in vitro dissolution method for the inhaled dry powder particles, fine particle dose collection methods, various in vitro dissolution testing methods developed for dry powder particles, and models commonly used to study absorption of inhaled drug. Full article
(This article belongs to the Special Issue Strategies to Enhance Drug Permeability across Biological Barriers)
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24 pages, 1500 KiB  
Review
Advancements in Skin Delivery of Natural Bioactive Products for Wound Management: A Brief Review of Two Decades
by Cameron Ryall, Sanjukta Duarah, Shuo Chen, Haijun Yu and Jingyuan Wen
Pharmaceutics 2022, 14(5), 1072; https://doi.org/10.3390/pharmaceutics14051072 - 17 May 2022
Cited by 21 | Viewed by 4147
Abstract
Application of modern delivery techniques to natural bioactive products improves their permeability, bioavailability, and therapeutic efficacy. Many natural products have desirable biological properties applicable to wound healing but are limited by their inability to cross the stratum corneum to access the wound. Over [...] Read more.
Application of modern delivery techniques to natural bioactive products improves their permeability, bioavailability, and therapeutic efficacy. Many natural products have desirable biological properties applicable to wound healing but are limited by their inability to cross the stratum corneum to access the wound. Over the past two decades, modern systems such as microneedles, lipid-based vesicles, hydrogels, composite dressings, and responsive formulations have been applied to natural products such as curcumin or aloe vera to improve their delivery and efficacy. This article reviews which natural products and techniques have been formulated together in the past two decades and the success of these applications for wound healing. Many cultures prefer natural-product-based traditional therapies which are often cheaper and more available than their synthetic counterparts. Improving natural products’ effect can provide novel wound-healing therapies for those who trust traditional compounds over synthetic drugs to reduce medical inequalities. Full article
(This article belongs to the Special Issue Strategies to Enhance Drug Permeability across Biological Barriers)
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14 pages, 1376 KiB  
Review
Application of CRISPR-Cas9 System to Study Biological Barriers to Drug Delivery
by Ji He, Riya Biswas, Piyush Bugde, Jiawei Li, Dong-Xu Liu and Yan Li
Pharmaceutics 2022, 14(5), 894; https://doi.org/10.3390/pharmaceutics14050894 - 20 Apr 2022
Cited by 3 | Viewed by 3663
Abstract
In recent years, sequence-specific clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems have been widely used in genome editing of various cell types and organisms. The most developed and broadly used CRISPR-Cas system, CRISPR-Cas9, has benefited from the proof-of-principle studies for a [...] Read more.
In recent years, sequence-specific clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems have been widely used in genome editing of various cell types and organisms. The most developed and broadly used CRISPR-Cas system, CRISPR-Cas9, has benefited from the proof-of-principle studies for a better understanding of the function of genes associated with drug absorption and disposition. Genome-scale CRISPR-Cas9 knockout (KO) screen study also facilitates the identification of novel genes in which loss alters drug permeability across biological membranes and thus modulates the efficacy and safety of drugs. Compared with conventional heterogeneous expression models or other genome editing technologies, CRISPR-Cas9 gene manipulation techniques possess significant advantages, including ease of design, cost-effectiveness, greater on-target DNA cleavage activity and multiplexing capabilities, which makes it possible to study the interactions between membrane proteins and drugs more accurately and efficiently. However, many mechanistic questions and challenges regarding CRISPR-Cas9 gene editing are yet to be addressed, ranging from off-target effects to large-scale genetic alterations. In this review, an overview of the mechanisms of CRISPR-Cas9 in mammalian genome editing will be introduced, as well as the application of CRISPR-Cas9 in studying the barriers to drug delivery. Full article
(This article belongs to the Special Issue Strategies to Enhance Drug Permeability across Biological Barriers)
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26 pages, 1604 KiB  
Review
Evaluation of Recent Intranasal Drug Delivery Systems to the Central Nervous System
by Tyler P. Crowe and Walter H. Hsu
Pharmaceutics 2022, 14(3), 629; https://doi.org/10.3390/pharmaceutics14030629 - 12 Mar 2022
Cited by 54 | Viewed by 8742
Abstract
Neurological diseases continue to increase in prevalence worldwide. Combined with the lack of modifiable risk factors or strongly efficacious therapies, these disorders pose a significant and growing burden on healthcare systems and societies. The development of neuroprotective or curative therapies is limited by [...] Read more.
Neurological diseases continue to increase in prevalence worldwide. Combined with the lack of modifiable risk factors or strongly efficacious therapies, these disorders pose a significant and growing burden on healthcare systems and societies. The development of neuroprotective or curative therapies is limited by a variety of factors, but none more than the highly selective blood-brain barrier. Intranasal administration can bypass this barrier completely and allow direct access to brain tissues, enabling a large number of potential new therapies ranging from bioactive peptides to stem cells. Current research indicates that merely administering simple solutions is inefficient and may limit therapeutic success. While many therapies can be delivered to some degree without carrier molecules or significant modification, a growing body of research has indicated several methods of improving the safety and efficacy of this administration route, such as nasal permeability enhancers, gelling agents, or nanocarrier formulations. This review shall discuss promising delivery systems and their role in expanding the clinical efficacy of this novel administration route. Optimization of intranasal administration will be crucial as novel therapies continue to be studied in clinical trials and approved to meet the growing demand for the treatment of patients with neurological diseases. Full article
(This article belongs to the Special Issue Strategies to Enhance Drug Permeability across Biological Barriers)
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21 pages, 15070 KiB  
Review
Delivery of Oligonucleotides: Efficiency with Lipid Conjugation and Clinical Outcome
by Phuc Tran, Tsigereda Weldemichael, Zhichao Liu and Hong-yu Li
Pharmaceutics 2022, 14(2), 342; https://doi.org/10.3390/pharmaceutics14020342 - 1 Feb 2022
Cited by 18 | Viewed by 6891
Abstract
Oligonucleotides have shifted drug discovery into a new paradigm due to their ability to silence the genes and inhibit protein translation. Importantly, they can drug the un-druggable targets from the conventional small-molecule perspective. Unfortunately, poor cellular permeability and susceptibility to nuclease degradation remain [...] Read more.
Oligonucleotides have shifted drug discovery into a new paradigm due to their ability to silence the genes and inhibit protein translation. Importantly, they can drug the un-druggable targets from the conventional small-molecule perspective. Unfortunately, poor cellular permeability and susceptibility to nuclease degradation remain as major hurdles for the development of oligonucleotide therapeutic agents. Studies of safe and effective delivery technique with lipid bioconjugates gains attention to resolve these issues. Our review article summarizes the physicochemical effect of well-studied hydrophobic moieties to enhance the cellular entry of oligonucleotides. The structural impacts of fatty acids, cholesterol, tocopherol, and squalene on cellular internalization and membrane penetration in vitro and in vivo were discussed first. The crucial assays for delivery evaluation within this section were analyzed sequentially. Next, we provided a few successful examples of lipid-conjugated oligonucleotides advanced into clinical studies for treating patients with different medical backgrounds. Finally, we pinpointed current limitations and outlooks in this research field along with opportunities to explore new modifications and efficacy studies. Full article
(This article belongs to the Special Issue Strategies to Enhance Drug Permeability across Biological Barriers)
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19 pages, 1460 KiB  
Review
Modulation of the Blood–Brain Barrier for Drug Delivery to Brain
by Liang Han
Pharmaceutics 2021, 13(12), 2024; https://doi.org/10.3390/pharmaceutics13122024 - 27 Nov 2021
Cited by 27 | Viewed by 4769
Abstract
The blood–brain barrier (BBB) precisely controls brain microenvironment and neural activity by regulating substance transport into and out of the brain. However, it severely hinders drug entry into the brain, and the efficiency of various systemic therapies against brain diseases. Modulation of the [...] Read more.
The blood–brain barrier (BBB) precisely controls brain microenvironment and neural activity by regulating substance transport into and out of the brain. However, it severely hinders drug entry into the brain, and the efficiency of various systemic therapies against brain diseases. Modulation of the BBB via opening tight junctions, inhibiting active efflux and/or enhancing transcytosis, possesses the potential to increase BBB permeability and improve intracranial drug concentrations and systemic therapeutic efficiency. Various strategies of BBB modulation have been reported and investigated preclinically and/or clinically. This review describes conventional and emerging BBB modulation strategies and related mechanisms, and safety issues according to BBB structures and functions, to try to give more promising directions for designing more reasonable preclinical and clinical studies. Full article
(This article belongs to the Special Issue Strategies to Enhance Drug Permeability across Biological Barriers)
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20 pages, 2645 KiB  
Review
Status Quo and Trends of Intra-Arterial Therapy for Brain Tumors: A Bibliometric and Clinical Trials Analysis
by Julian S. Rechberger, Frederic Thiele and David J. Daniels
Pharmaceutics 2021, 13(11), 1885; https://doi.org/10.3390/pharmaceutics13111885 - 6 Nov 2021
Cited by 12 | Viewed by 2613
Abstract
Intra-arterial drug delivery circumvents the first-pass effect and is believed to increase both efficacy and tolerability of primary and metastatic brain tumor therapy. The aim of this update is to report on pertinent articles and clinical trials to better understand the research landscape [...] Read more.
Intra-arterial drug delivery circumvents the first-pass effect and is believed to increase both efficacy and tolerability of primary and metastatic brain tumor therapy. The aim of this update is to report on pertinent articles and clinical trials to better understand the research landscape to date and future directions. Elsevier’s Scopus and ClinicalTrials.gov databases were reviewed in August 2021 for all possible articles and clinical trials of intra-arterial drug injection as a treatment strategy for brain tumors. Entries were screened against predefined selection criteria and various parameters were summarized. Twenty clinical trials and 271 articles satisfied all inclusion criteria. In terms of articles, 201 (74%) were primarily clinical and 70 (26%) were basic science, published in a total of 120 different journals. Median values were: publication year, 1986 (range, 1962–2021); citation count, 15 (range, 0–607); number of authors, 5 (range, 1–18). Pertaining to clinical trials, 9 (45%) were phase 1 trials, with median expected start and completion years in 2011 (range, 1998–2019) and 2022 (range, 2008–2025), respectively. Only one (5%) trial has reported results to date. Glioma was the most common tumor indication reported in both articles (68%) and trials (75%). There were 215 (79%) articles investigating chemotherapy, while 13 (65%) trials evaluated targeted therapy. Transient blood–brain barrier disruption was the commonest strategy for articles (27%) and trials (60%) to optimize intra-arterial therapy. Articles and trials predominately originated in the United States (50% and 90%, respectively). In this bibliometric and clinical trials analysis, we discuss the current state and trends of intra-arterial therapy for brain tumors. Most articles were clinical, and traditional anti-cancer agents and drug delivery strategies were commonly studied. This was reflected in clinical trials, of which only a single study had reported outcomes. We anticipate future efforts to involve novel therapeutic and procedural strategies based on recent advances in the field. Full article
(This article belongs to the Special Issue Strategies to Enhance Drug Permeability across Biological Barriers)
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Other

32 pages, 2338 KiB  
Systematic Review
Ultrasound-Mediated Blood–Brain Barrier Disruption for Drug Delivery: A Systematic Review of Protocols, Efficacy, and Safety Outcomes from Preclinical and Clinical Studies
by Kushan Gandhi, Anita Barzegar-Fallah, Ashik Banstola, Shakila B. Rizwan and John N. J. Reynolds
Pharmaceutics 2022, 14(4), 833; https://doi.org/10.3390/pharmaceutics14040833 - 11 Apr 2022
Cited by 32 | Viewed by 3471 | Correction
Abstract
Ultrasound-mediated blood–brain barrier (BBB) disruption has garnered focus as a method of delivering normally impenetrable drugs into the brain. Numerous studies have investigated this approach, and a diverse set of ultrasound parameters appear to influence the efficacy and safety of this approach. An [...] Read more.
Ultrasound-mediated blood–brain barrier (BBB) disruption has garnered focus as a method of delivering normally impenetrable drugs into the brain. Numerous studies have investigated this approach, and a diverse set of ultrasound parameters appear to influence the efficacy and safety of this approach. An understanding of these findings is essential for safe and reproducible BBB disruption, as well as in identifying the limitations and gaps for further advancement of this drug delivery approach. We aimed to collate and summarise protocols and parameters for achieving ultrasound-mediated BBB disruption in animal and clinical studies, as well as the efficacy and safety methods and outcomes associated with each. A systematic search of electronic databases helped in identifying relevant, included studies. Reference lists of included studies were further screened to identify supplemental studies for inclusion. In total, 107 articles were included in this review, and the following parameters were identified as influencing efficacy and safety outcomes: microbubbles, transducer frequency, peak-negative pressure, pulse characteristics, and the dosing of ultrasound applications. Current protocols and parameters achieving ultrasound-mediated BBB disruption, as well as their associated efficacy and safety outcomes, are identified and summarised. Greater standardisation of protocols and parameters in future preclinical and clinical studies is required to inform robust clinical translation. Full article
(This article belongs to the Special Issue Strategies to Enhance Drug Permeability across Biological Barriers)
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