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Intrathecal drug delivery in the era of nanomedicine.

ABSTRACT: Administration of substances directly into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord is one approach that can circumvent the blood-brain barrier to enable drug delivery to the central nervous system (CNS). However, molecules that have been administered by intrathecal injection, which includes intraventricular, intracisternal, or lumbar locations, encounter new barriers within the subarachnoid space. These barriers include relatively high rates of turnover as CSF clears and potentially inadequate delivery to tissue or cellular targets. Nanomedicine could offer a solution. In contrast to the fate of freely administered drugs, nanomedicine systems can navigate the subarachnoid space to sustain delivery of therapeutic molecules, genes, and imaging agents within the CNS. Some evidence suggests that certain nanomedicine agents can reach the parenchyma following intrathecal administration. Here, we will address the preclinical and clinical use of intrathecal nanomedicine, including nanoparticles, microparticles, dendrimers, micelles, liposomes, polyplexes, and other colloidalal materials that function to alter the distribution of molecules in tissue. Our review forms a foundational understanding of drug delivery to the CSF that can be built upon to better engineer nanomedicine for intrathecal treatment of disease.

SUBMITTER: Fowler MJ

PROVIDER: S-EPMC8182643 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Intrathecal drug delivery in the era of nanomedicine.

Fowler M J MJ Cotter J D JD Knight B E BE Sevick-Muraca E M EM Sandberg D I DI Sirianni R W RW

Advanced drug delivery reviews 20200303

Administration of substances directly into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord is one approach that can circumvent the blood-brain barrier to enable drug delivery to the central nervous system (CNS). However, molecules that have been administered by intrathecal injection, which includes intraventricular, intracisternal, or lumbar locations, encounter new barriers within the subarachnoid space. These barriers include relatively high rates of turnover as CSF clea ...[more]

PMID: 32142739

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Project description:Cancer continues to be one of the most difficult global healthcare problems. Although there is a large library of drugs that can be used in cancer treatment, the problem is selectively killing all the cancer cells while reducing collateral toxicity to healthy cells. There are several biological barriers to effective drug delivery in cancer such as renal, hepatic, or immune clearance. Nanoparticles loaded with drugs can be designed to overcome these biological barriers to improve efficacy while reducing morbidity. Nanomedicine has ushered in a new era for drug delivery by improving the therapeutic indices of the active pharmaceutical ingredients engineered within nanoparticles. First generation nanomedicines have received widespread clinical approval over the past two decades, from Doxil® (liposomal doxorubicin) in 1995 to Onivyde® (liposomal irinotecan) in 2015. This review highlights the biological barriers to effective drug delivery in cancer, emphasizing the need for nanoparticles for improving therapeutic outcomes. A summary of different nanoparticles used for drug delivery applications in cancer are presented. The review summarizes recent successes in cancer nanomedicine in the clinic. The clinical trials of Onivyde leading to its approval in 2015 by the Food and Drug Adminstration are highlighted as a case study in the recent clinical success of nanomedicine against cancer. Next generation nanomedicines need to be better targeted to specifically destroy cancerous tissue, but face several obstacles in their clinical development, including identification of appropriate biomarkers to target, scale-up of synthesis, and reproducible characterization. These hurdles need to be overcome through multidisciplinary collaborations across academia, pharmaceutical industry, and regulatory agencies in order to achieve the goal of eradicating cancer. This review discusses the current use of clinically approved nanomedicines, the investigation of nanomedicines in clinical trials, and the challenges that may hinder development of the nanomedicines for cancer treatment.

Project description:BackgroundThe emergence of nanomedicine in the past decade has changed the landscape of disease diagnosis and treatment. Nanomedicine makes use of nanostructures for applications in different fields of medicine, including drug delivery, biosensors, neuro-electronic interfaces, in vivo imaging, and cell-specific molecular interactions. Despite its relative infancy, nanomedicine has generated a significant body of research as evidenced by peer reviewed literature and several patents. This proposed systematic review will focus specifically on drug delivery systems in which nanoparticles are used to enhance the pharmacological and therapeutic properties of drugs. The strength of nanoparticulate drug delivery systems is their ability to alter the pharmacokinetics and bio-distribution of drugs. Globally, the discourse on nanomedicine is dominated by research being done in the developed countries of Europe and in the United States of America. Less attention has been given to the applications of nanomedicine in developing countries, particularly Africa. There is dearth of information on the applications of nanomedicine in terms of drug delivery with particular reference to which diseases are being targeted generally in Africa. The review will describe the specific diseases that are being targeted and the progress being made in South Africa, with a view to determining whether the applications of nanomedicine are being appropriated to address the context-specific challenges in this country or if they mimic what is being done globally.MethodsKeywords related to nanomedicine and drug delivery will be combined to build a search strategy for each of the following databases: PubMed, Cochrane Library (including Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, Cochrane Methodology Register), Google Scholar, NHS Health Technology Assessment Database and Web of Science. We will also check reference lists of included studies for other eligible reports and search unpublished data. To ensure that the search is comprehensive, grey literature will be searched extensively. Literature to be included will have nanomedicine in drug delivery as the primary application and report on the specific diseases that are targeted in South Africa. Two authors will independently screen the search output, select studies and extract data; discrepancies will be resolved by consensus and discussion. When no consensus is reached, the third author will be consulted DISCUSSION: The systematic review will inform the government, policy-makers, investors, health professionals, scientists, and engineers about the applications of nanomedicine in drug delivery. In particular, it will identify the diseases targeted by the application of nanomedicine for drug delivery and the progress being made in South Africa as the disease burden of this country differs from that of developed countries where nanomedicine has been widely used for drug delivery.Systematic review registrationPROSPERO CRD42017057388.

Dataset Information

Intrathecal drug delivery in the era of nanomedicine.

Publications

Intrathecal drug delivery in the era of nanomedicine.

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