Using Polymer Chemistry to Modulate the Delivery of Neurotrophic Factors from Degradable Microspheres: Delivery of BDNF

Bertram, James P.; Rauch, Millicent Ford; Chang, Kaliq; Lavik, Erin B.

doi:10.1007/s11095-009-0009-x

Cited by 46 publications

(38 citation statements)

References 49 publications

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“…The solution remaining in the dialysis tube was freeze-dried for 3 days to produce activated PEG-CDI. 17 Then using an excess of activated CDI-PEG-CDI with PLGA-PLL side primary amino chain reaction, the process of polymer dissolution and precipitation was repeated three times until the unconjugated PEG was removed, eventually forming PEG-PLL-PLGA. 18 The drug (DNR, Tet, and NIR797 dye) was directly added into the inner aqueous solution to prepare the drug-loaded PEG-PLL-PLGA.…”

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confidence: 99%

Targeted multidrug-resistance reversal in tumor based on PEG-PLL-PLGA polymer nano drug delivery system

Guo

Zhang

Wang

et al. 2015

IJN

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The study investigated the reversal of multidrug resistance (MDR) and the biodistribution of nanoparticles (NPs) that target leukemia cells in a nude mice model via a surface-bound transferrin (Tf). The cytotoxic cargo of daunorubicin (DNR) and tetrandrine (Tet) was protected in the NPs by an outer coat composed of polyethylene glycol (PEG)-poly- l -lysine (PLL)-poly(lactic- co -glycolic acid) (PLGA) NPs. Injection of DNR-Tet-Tf-PEG-PLL-PLGA NPs into nude mice bearing MDR leukemia cell K562/A02 xenografts was shown to inhibit tumor growth, and contemporaneous immunohistochemical analysis of tumor tissue showed the targeted NPs induced apoptosis in tumor cells. Targeted tumor cells exhibited a marked increase in Tf receptor expression, with noticeable decreases in P-glycoprotein, MDR protein, and nuclear factor κB, as assessed by quantitative real-time polymerase chain reaction and Western blot analysis. Moreover, the concentration of DNR was shown to increase in plasma, tumor tissue, and major organs. Flow cytometry analysis with a near-infrared fluorescent (NIRF) dye, NIR797, was used to study the effectiveness of Tf as a targeting group for leukemia cells, a finding that was supported by NIRF imaging in tumor-bearing nude mice. In summary, our studies show that DNR-Tet-Tf-PEG-PLL-PLGA NPs provide a specific and effective means to target cytotoxic drugs to MDR tumor cells.

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confidence: 99%

Targeted multidrug-resistance reversal in tumor based on PEG-PLL-PLGA polymer nano drug delivery system

Guo

Zhang

Wang

et al. 2015

IJN

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“…IGF-I was continuously released from the microspheres, which likely increased the brain levels of IGF-I over a period of time and resulted in therapeutic effects similar to a continuous subcutaneous infusion of IGF-I [415, 416]. Another study reported a sustained release for up to 60 days of a therapeutic protein, BDNF from PLGA-poly( L-lysine)-PEG microspheres [417]. Although in vivo test was not reported, the bioactivity of the released BDNF was confirmed by cell proliferation and neurite outgrowth in pheochromocytoma PC12 cells stably expressing BDNF cognate receptor TrkB [417].…”

Section: Particle-based Carriers For Cns Delivery Of Proteinsmentioning

confidence: 99%

“…Another study reported a sustained release for up to 60 days of a therapeutic protein, BDNF from PLGA-poly( L-lysine)-PEG microspheres [417]. Although in vivo test was not reported, the bioactivity of the released BDNF was confirmed by cell proliferation and neurite outgrowth in pheochromocytoma PC12 cells stably expressing BDNF cognate receptor TrkB [417]. …”

Section: Particle-based Carriers For Cns Delivery Of Proteinsmentioning

confidence: 99%

Agile delivery of protein therapeutics to CNS

Xiang

Manickam

Brynskikh

et al. 2014

Journal of Controlled Release

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A variety of therapeutic proteins have shown potential to treat central nervous system (CNS) disorders. Challenge to deliver these protein molecules to the brain is well known. Proteins administered through parenteral routes are often excluded from the brain because of their poor bioavailability and the existence of the blood-brain barrier (BBB). Barriers also exist to proteins administered through non-parenteral routes that bypass the BBB. Several strategies have shown promise in delivering proteins to the brain. This review, first, describes the physiology and pathology of the BBB that underscore the rationale and needs of each strategy to be applied. Second, major classes of protein therapeutics along with some key factors that affect their delivery outcomes are presented. Third, different routes of protein administration (parenteral, central intracerebroventricular and intraparenchymal, intranasal and intrathecal) are discussed along with key barriers to CNS delivery associated with each route. Finally, current delivery strategies involving chemical modification of proteins and use of particle-based carriers are overviewed using examples from literature and our own work. Whereas most of these studies are in the early stage, some provide proof of mechanism of increased protein delivery to the brain in relevant models of CNS diseases, while in few cases proof of concept had been attained in clinical studies. This review will be useful to broad audience of students, academicians and industry professionals who consider critical issues of protein delivery to the brain and aim developing and studying effective brain delivery systems for protein therapeutics.

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“…Drug release is typically dependent on the biodegradation of the material, which can last from hours to months and invoke a host glia response [12][13][14][15]. Drug release is typically dependent on the biodegradation of the material, which can last from hours to months and invoke a host glia response [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

“…Drug release is typically dependent on the biodegradation of the material, which can last from hours to months and invoke a host glia response [12][13][14][15]. Certain factors, such as brain-derived neuronal growth factor, provide neuroprotection and may support neuroplasticity [12,18], whereas other factors, such as vascular endothelial growth factor (VEGF), potentially also strongly affect angiogenesis [19 && ]. Certain factors, such as brain-derived neuronal growth factor, provide neuroprotection and may support neuroplasticity [12,18], whereas other factors, such as vascular endothelial growth factor (VEGF), potentially also strongly affect angiogenesis [19 && ].…”

Section: Introductionmentioning

confidence: 99%