Novel Advances in Drug Delivery to Brain Cancer

2005 ◽  
Vol 4 (4) ◽  
pp. 417-428 ◽  
Author(s):  
Maciej S. Lesniak
Keyword(s):  
Drug Delivery ◽  
Brain Tumors ◽  
Tumor Therapy ◽  
Chemotherapeutic Agents ◽  
Controlled Delivery ◽  
Local Drug Delivery ◽  
Delivery Methods ◽  
Malignant Brain Tumors ◽  
Direct Exposure ◽  
The Brain

The therapy of brain tumors has been limited by a lack of effective methods of drug delivery to the brain. Systemic administration is often associated with toxic side effects and ultimately fails to achieve therapeutic concentrations within a tumor. An attractive strategy that has gained importance in brain tumor therapy has relied on local and controlled delivery of chemotherapeutic agents by biodegradable polymers. This technique allows direct exposure of tumor cells to a therapeutic agent for a prolonged period of time and has been shown to prolong the survival of patients with malignant brain tumors. The use of polymers for local drug delivery greatly expands the spectrum of drugs available for the treatment of malignant brain tumors. This review discusses the rationale for local drug delivery, describes the development of currently available polymer-based therapeutic agents, and highlights examples of promising non-polymer based drug delivery methods for use in the treatment of malignant brain tumors.

scholarly journals Focused Ultrasound Strategies for Brain Tumor Therapy

2019 ◽  
Vol 19 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Adomas Bunevicius ◽  
Nathan Judson McDannold ◽  
Alexandra J Golby
Keyword(s):  
Brain Tumors ◽  
Viral Vectors ◽  
Focused Ultrasound ◽  
Tumor Therapy ◽  
Drug Distribution ◽  
Low Frequency ◽  
Tissue Level ◽  
Chemotherapeutic Agents ◽  
Promising Tool ◽  
Investigational Agents

Abstract BACKGROUND A key challenge in the medical treatment of brain tumors is the limited penetration of most chemotherapeutic agents across the blood–brain barrier (BBB) into the tumor and the infiltrative margin around the tumor. Magnetic resonance-guided focused ultrasound (MRgFUS) is a promising tool to enhance the delivery of chemotherapeutic agents into brain tumors. OBJECTIVE To review the mechanism of FUS, preclinical evidence, and clinical studies that used low-frequency FUS for a BBB opening in gliomas. METHODS Literature review. RESULTS The potential of externally delivered low-intensity ultrasound for a temporally and spatially precise and predictable disruption of the BBB has been investigated for over a decade, yielding extensive preclinical literature demonstrating that FUS can disrupt the BBB in a spatially targeted and temporally reversible manner. Studies in animal models documented that FUS enhanced the delivery of numerous chemotherapeutic and investigational agents across the BBB and into brain tumors, including temozolomide, bevacizumab, 1,3-bis (2-chloroethyl)-1-nitrosourea, doxorubicin, viral vectors, and cells. Chemotherapeutic interventions combined with FUS slowed tumor progression and improved animal survival. Recent advances of MRgFUS systems allow precise, temporally and spatially controllable, and safe transcranial delivery of ultrasound energy. Initial clinical evidence in glioma patients has shown the efficacy of MRgFUS in disrupting the BBB, as demonstrated by an enhanced gadolinium penetration. CONCLUSION Thus far, a temporary disruption of the BBB followed by the administration of chemotherapy has been both feasible and safe. Further studies are needed to determine the actual drug delivery, including the drug distribution at a tissue-level scale, as well as effects on tumor growth and patient prognosis.

scholarly journals Status Quo and Trends of Intra-Arterial Therapy for Brain Tumors: A Bibliometric and Clinical Trials Analysis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1885
Author(s):  
Julian S. Rechberger ◽  
Frederic Thiele ◽  
David J. Daniels
Keyword(s):  
Drug Delivery ◽  
Clinical Trials ◽  
Brain Tumors ◽  
Phase 1 ◽  
Citation Count ◽  
Tumor Therapy ◽  
The United States ◽  
Blood Brain Barrier Disruption ◽  
Current State ◽  
Brain Barrier Disruption

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.

scholarly journals Overview of Current Drug Delivery Methods Across the Blood–Brain Barrier for the Treatment of Primary Brain Tumors

CNS Drugs ◽  
2020 ◽  
Vol 34 (11) ◽  
pp. 1121-1131 ◽  
Author(s):  
Rianne Haumann ◽  
Jessica Carvalho Videira ◽  
Gertjan J. L. Kaspers ◽  
Dannis G. van Vuurden ◽  
Esther Hulleman
Keyword(s):  
Drug Delivery ◽  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Delivery Methods ◽  
Primary Brain Tumors ◽  
Current Drug ◽  
Blood Brain

Hyperthermia for Brain Tumors

Neurosurgery ◽  
1981 ◽  
Vol 9 (3) ◽  
pp. 327-335 ◽  
Author(s):  
Michael Salcman ◽  
George M. Samaras
Keyword(s):  
Brain Tumors ◽  
Thermal Sensitivity ◽  
Antineoplastic Agent ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Cellular Level ◽  
Growth Fraction ◽  
Combined Modality Treatment ◽  
Clinical Safety ◽  
Malignant Brain Tumors

Abstract Hyperthermia has great potential as an antineoplastic agent because: (a) it is effective against relatively radioresistant hypoxic cells and cells in S phase: (b) unlike most chemotherapeutic agents. it is effective against poorly vascularized and metabolically quiescent tissues; (c) as a physical agent, its biological effect is related to the duration and intensity of its application; (d) it seems to have no cumulative toxicity; and (e) it potentiates the effects of both chemotherapy and ionizing radiation at the cellular level. The use of hyperthermia for malignant brain tumors is constrained by a relatively narrow therapeutic index and the considerable thermal sensitivity of normal neural tissue. Glioblastoma multiforme, by virtue of its low growth fraction and heterogeneous cell populations, seems to be an ideal candidate for hyperthermia administered as part of a combined modality treatment program. Focal hyperthermia can be produced by a number of energy sources, including those utilizing ultrasound, microwave, and radiofrequency generators. The clinical safety and feasibility of a miniature microwave radiator/sensor system for direct implantation have been demonstrated. In comparison to normal feline brain, malignant brain tumors in humans are unable to dissipate heat efficiently.

scholarly journals Implantable Slow-Release Chemotherapeutic Polymers for the Treatment of Malignant Brain Tumors

1998 ◽  
Vol 5 (2) ◽  
pp. 130-137 ◽  
Author(s):  
Prakash Sampath ◽  
Henry Brem
Keyword(s):  
Brain Tumors ◽  
Slow Release ◽  
Malignant Gliomas ◽  
Polymer System ◽  
Chemotherapeutic Agents ◽  
Local Concentration ◽  
Malignant Brain Tumors ◽  
Polymeric Delivery ◽  
Double Blinded ◽  
Controlled Release Polymer

Background: Despite significant advances in neurosurgery, radiation therapy, and chemotherapy, the prognosis for patients with malignant brain tumors remains dismal. In an effort to improve control of local disease, we have developed a biodegradable, controlled-release polymer that is implanted directly at the tumor site. Methods: The preclinical and clinical development of the polymeric delivery of chemotherapeutic agents for treatment of patients with malignant gliomas is reviewed. Results: Carmustine (BCNU)-impregnated biodegradable polymer is the first new therapy approved by the FDA for patients with gliomas in 23 years. This delivery system provides high local concentration of drug with minimal systemic toxicity and obviates the need for drug to cross the blood-brain barrier. Randomized, multi-institutional, double-blinded, placebo-controlled studies have shown improved survival in patients treated for gliomas both at initial presentation and at recurrence. Several clinical principles have emerged from the use of this polymer system, and further applications are currently being investigated. Conclusions: Local delivery of therapeutic agents via biodegradable polymers may play an increasing role in patients with brain tumors.

Silk and PEG as means to stiffen a parylene probe for insertion in the brain: toward a double time-scale tool for local drug delivery

2015 ◽  
Vol 25 (12) ◽  
pp. 125003 ◽  
Author(s):  
A Lecomte ◽  
V Castagnola ◽  
E Descamps ◽  
L Dahan ◽  
M C Blatché ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Time Scale ◽  
Local Drug Delivery ◽  
Double Time ◽  
The Brain

scholarly journals The Use of Heptamethine Cyanine Dyes as Drug-Conjugate Systems in the Treatment of Primary and Metastatic Brain Tumors

2021 ◽  
Vol 11 ◽  
Author(s):  
Elizabeth Cooper ◽  
Peter J. Choi ◽  
William A. Denny ◽  
Jiney Jose ◽  
Mike Dragunow ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Brain Tumors ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Drug Carrier ◽  
Cancer Therapeutics ◽  
Cyanine Dyes ◽  
Chemotherapeutic Agents ◽  
Metastatic Brain Tumors ◽  
Specific Distribution

Effective cancer therapeutics for brain tumors must be able to cross the blood-brain barrier (BBB) to reach the tumor in adequate quantities and overcome the resistance conferred by the local tumor microenvironment. Clinically approved chemotherapeutic agents have been investigated for brain neoplasms, but despite their effectiveness in peripheral cancers, failed to show therapeutic success in brain tumors. This is largely due to their poor bioavailability and specificity towards brain tumors. A targeted delivery system might improve the efficacy of the candidate compounds by increasing the retention time in the tumor tissue, and minimizing the numerous side effects associated with the non-specific distribution of the chemotherapy agent. Heptamethine cyanine dyes (HMCDs) are a class of near-infrared fluorescence (NIRF) compounds that have recently emerged as promising agents for drug delivery. Initially explored for their use in imaging and monitoring neoplasms, their tumor-targeting properties have recently been investigated for their use as drug carrier systems. This review will explore the recent developments in the tumour-targeting properties of a specific group of NIRF cyanine dyes and the preclinical evidence for their potential as drug-delivery systems in the treatment of primary and metastatic brain tumors.

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