Various drug delivery approaches to the central nervous system

Pasha, Santosh; Gupta, K. C.

doi:10.1517/17425240903405581

Cited by 30 publications

(33 citation statements)

References 131 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nine days later, the f-Gd 3 N@C 80 nanoplatform (0.25 mmol/L) was infused into the intracerebral tumor with CED by using a microinjection pump (Bioanalytical Systems, West Lafayette, Ind) at a rate of 0.2 µL/min for a total of 18 m L. The combination of the 28-gauge needle, aqueous infusate medium, and slow fl ow rate (0.2 µL/min) has been shown to provide effi cient CED in rodent models ( 14 ). Animals underwent T1-and T2-weighted MR imaging 1 day before blood-brain barrier, which makes systemic (intravenous) administration of drugs generally ineffi cient for cancers of the central nervous system.…”

Section: Agent Infusion and Mr Imaging Studiesmentioning

confidence: 99%

Metallofullerene-based Nanoplatform for Brain Tumor Brachytherapy and Longitudinal Imaging in a Murine Orthotopic Xenograft Model

Shultz¹,

Wilson²,

Fuller³

et al. 2011

Radiology

View full text Add to dashboard Cite

Purpose:To demonstrate in an orthotopic xenograft brain tumor model that a functionalized metallofullerene (f-Gd 3 N@C 80 ) can enable longitudinal tumor imaging and, when radiolabeled with lutetium 177 ( 177 Lu) and tetraazacyclododecane tetraacetic acid (DOTA ) ( 177 Lu-DOTA-f-Gd 3 N@C 80 ), provide an anchor to deliver effective brachytherapy. Materials and Methods:All experiments involving the use of mice were carried out in accordance with protocols approved by the institutional animal care and use committee. Human glioblastoma U87MG cells were implanted by using stereotactic procedures into the brains of 37 female athymic nude-Foxn1nu mice and allowed to develop into a tumor for 8 days . T1-and T2-weighted magnetic resonance (MR) imaging was performed in fi ve mice. Biodistribution studies were performed in 12 mice at four time points over 7 days to evaluate gadolinium content. Survival studies involved 20 mice that received infusion of a nanoplatform by means of convectionenhanced delivery (CED) 8 days after tumor implantation. Mice in survival studies were divided into two groups: one comprised untreated mice that received f-Gd 3 N@C 80 alone and the other comprised mice treated with brachytherapy that received 1.11 MBq of 177 Lu-DOTA-f-Gd 3 N@C 80 . Survival data were evaluated by using Kaplan-Meier statistical methods. Results:MR imaging showed extended tumor retention (25.6% 6 1.2 of the infused dose at 52 days, confi rmed with biodistribution studies) of the f-Gd 3 N@C 80 nanoplatform, which enabled longitudinal imaging. Successful coupling of 177 Lu to the f-Gd 3 N@C 80 surface was achieved by using a bifunctional macrocyclic chelator. The extended tumor retention allowed for effective brachytherapy , as indicated by extended survival time ( . 2.5 times that of the untreated group) and histologic signs of radiation-induced tumor damage. Conclusion:The

show abstract

Section: Agent Infusion and Mr Imaging Studiesmentioning

confidence: 99%

Metallofullerene-based Nanoplatform for Brain Tumor Brachytherapy and Longitudinal Imaging in a Murine Orthotopic Xenograft Model

Shultz¹,

Wilson²,

Fuller³

et al. 2011

Radiology

View full text Add to dashboard Cite

show abstract

“…In vivo experiments are needed to design antibody fragments that have a high selectivity and specificity, and that permeate the designated tissue following direct intralesional application. In general, we need to exploit new methods for the noninvasive, specific application of active molecules (Pasha & Gupta, 2010).…”

Section: Proposalmentioning

confidence: 99%

Consensus Document on European Brain Research

Luca

Baker

Corradetti

et al. 2011

European Journal of Neuroscience

View full text Add to dashboard Cite

Psychiatric and neurological diseases combined represent a considerable social and economic burden in Europe. A recent study conducted by the European Brain Council (EBC) quantified the 'cost and burden' of major brain diseases in Europe, amounting to €386bn per year. Considering that these costs will increase exponentially in the years to come due to ageing of the European population, it is necessary to act now in order to curb this increase and possibly reverse the trend. Thus, establishing a strong European platform supporting basic and clinical research in neuroscience is needed to confront the economic and social challenge posed by management of brain diseases in European countries. To setup a platform for discussion, EBC published in 2006 a Consensus Document on European Brain Research, describing needs and achievements of research in Europe and presenting proposals for future research programs. Since 2006, European research in neuroscience has advanced tremendously. The present document represents an update elaborated to reflect changes in research priorities and advances in brain research that have taken place since 2006. The same approach and format have been used here as in the previous version. Multinational and multidisciplinary teams have once again come together to express their views, not only on the current strengths in European research, but also on what needs to be done in priority, hoping that this update will inspire policy makers and stakeholders in directing funding for research in Europe.

show abstract

“…The major BBB physiological functions comprise sustaining homeostasis at the brain parenchyma and protecting the brain from potentially harmful substances. The BBB is formed principally from capillary endothelial cells without fenestrations that are closely joined together by tight intercellular junctions presenting high trans-endothelial electrical resistance compared with other tissues and thereby efficiently restrict the paracellular diffusion of solutes or drugs [2]. Another barrier that limits brain drug delivery is the blood cerebrospinal fluid barrier (BCSFB) that separates the blood from the cerebrospinal fluid.…”

Section: Introductionmentioning

confidence: 99%

“…Another barrier that limits brain drug delivery is the blood cerebrospinal fluid barrier (BCSFB) that separates the blood from the cerebrospinal fluid. The CNS also presents functional barriers in the form of influx and efflux transporter mechanisms, which are responsible for the inclusion and exclusion of solutes/therapeutics into and out of the CNS [2].…”

Section: Introductionmentioning

confidence: 99%

“…In order to cross the BBB by passive diffusion, molecules should be relatively small, present a molecular mass of < 400 Da, a log octanol/water partition coefficient between -0.5 and 6.0, be lipid-soluble, be either neutral or significantly uncharged at physiological pH 7.4, and be capable of forming < 8 H-bonds with water [2]. Unfortunately, only a few drugs fulfil these requirements and the overwhelming majority of small molecules, proteins and peptides do not cross the BBB.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Brain Drug Delivery Systems for Neurodegenerative Disorders

Garbayo

Ansorena

Blanco-Prieto

2012

CPB

View full text Add to dashboard Cite

Neurodegenerative disorders (NDs) are rapidly increasing as population ages. However, successful treatments for NDs have so far been limited and drug delivery to the brain remains one of the major challenges to overcome. There has recently been growing interest in the development of drug delivery systems (DDS) for local or systemic brain administration. DDS are able to improve the pharmacological and therapeutic properties of conventional drugs and reduce their side effects. The present review provides a concise overview of the recent advances made in the field of brain drug delivery for treating neurodegenerative disorders. Examples include polymeric micro and nanoparticles, lipidic nanoparticles, pegylated liposomes, microemulsions and nanogels that have been tested in experimental models of Parkinson's, Alzheimer's and Hungtinton's disease. Overall, the results reviewed here show that DDS have great potential for NDs treatment.

show abstract

Various drug delivery approaches to the central nervous system

Cited by 30 publications

References 131 publications

Metallofullerene-based Nanoplatform for Brain Tumor Brachytherapy and Longitudinal Imaging in a Murine Orthotopic Xenograft Model

Metallofullerene-based Nanoplatform for Brain Tumor Brachytherapy and Longitudinal Imaging in a Murine Orthotopic Xenograft Model

Consensus Document on European Brain Research

Brain Drug Delivery Systems for Neurodegenerative Disorders

Contact Info

Product

Resources

About