Development of ALZET® osmotic pump compatible solvent compositions to solubilize poorly soluble compounds for preclinical studies

Gullapalli, Rampurna P.; Wong, Angelina; Brigham, Elizabeth F.; Kwong, Grace; Wadsworth, Angie; Willits, C. O.; Quinn, Kevin P.; Goldbach, Erich; Samant, Bhushan

doi:10.3109/10717544.2012.691121

Cited by 17 publications

(9 citation statements)

References 19 publications

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“…K777 formulation and systemic treatment of mice by injection or Alzet pump infusion K777-HCl doses and formulations were as follows: DMSO (10%)/dextrose (5%)/water (85%) for i.v. (100 ml = 62.5 mg/kg for ;20-g mice) or s.c. (200 ml = 125 mg/kg for ;20-g mice), and polyethyleneglycol-300 (25%)/ Glycofurol (25%)/Cremophor ELP (25%)/ethanol (15%)/propylene glycol (10%) [52] for Alzet pumps (model 2001; Direct Corporation, Cupertino, CA, USA), which were surgically implanted s.c. on the backs of mice for 1 wk, delivering drug or excipient formulation at a rate of 1 ml/h for the indicated doses of K777. All excipient ingredients used for K777 formulation were purchased from Sigma-Aldrich (St. Louis, MO).…”

Section: Production and Measurement Of Il-1b Tnf-a And Cell Death Assayed With In Vitro Culturesmentioning

confidence: 99%

Frontline Science: Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1β activation

Orlowski

Sharma

Colbert

et al. 2017

Journal of Leukocyte Biology

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Sterile particles cause several chronic, inflammatory diseases, characterized by repeating cycles of particle phagocytosis and inflammatory cell death. Recent studies have proposed that these processes are driven by the NLRP3 inflammasome, a platform activated by phagocytosed particles, which controls both caspase-1-dependent cell death (pyroptosis) and mature IL-1β secretion. After phagocytosis, particles can disrupt lysosomes, and inhibitor studies have suggested that the resulting release of a lysosomal protease-cathepsin B-into the cytosol somehow activates NLRP3. However, using primary murine macrophages, we found that particle-induced cell death occurs independent of NLRP3/caspase-1 and depends instead on multiple, redundant cathepsins. In contrast, nigericin, a soluble activator of NLRP3 inflammasomes, induced cell death that was dependent on the NLRP3. Interestingly, nigericin-induced cell death depended partly on a single cathepsin, cathepsin X. By inhibiting or silencing multiple cathepsins in macrophages, several key proinflammatory events induced by sterile particles are blocked, including cell death, pro-IL-1β production, and IL-1β secretion. These data suggest that cathepsins might be potential therapeutic targets in particulate-mediated inflammatory disease. In support of this concept, we find that a broad-spectrum cathepsin inhibitor can suppress particle-induced IL-1-dependent peritonitis.

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Section: Production and Measurement Of Il-1b Tnf-a And Cell Death Assayed With In Vitro Culturesmentioning

confidence: 99%

Frontline Science: Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1β activation

Orlowski

Sharma

Colbert

et al. 2017

Journal of Leukocyte Biology

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“…injection is not considered the preferred choice for targeting the brain, as it induces stress in rodents and requires high doses of drugs [23,24]. In this context, mini-osmotic pumps represent an ideal system for studying long-term treatments in the brain, at a fixed known delivery rate that eludes the problem of daily injection stress in animals and overcomes the BBB by direct intracerebroventricular administration [17,18,25,26].…”

Section: Discussionmentioning

confidence: 99%

“…The operation of mini-osmotic pumps, e.g., manufactured by ALZET, is based on the salt layer compartment and the tissue environment in which the pump is implanted. The high osmolality of the salt layer causes water influx from the tissue trough a semipermeable membrane [18].…”

Section: Introductionmentioning

confidence: 99%

A New Tool for the Analysis of the Effect of Intracerebrally Injected Anti-Amyloid-β Compounds

Upīte

Brüning

Möhle

et al. 2021

JAD

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Background: A wide range of techniques has been developed over the past decades to characterize amyloid-β (Aβ) pathology in mice. Until now, no method has been established to quantify spatial changes in Aβ plaque deposition due to targeted delivery of substances using ALZET ® pumps. Objective: Development of a methodology to quantify the local distribution of Aβ plaques after intracerebral infusion of compounds. Methods: We have developed a toolbox to quantify Aβ plaques in relation to intracerebral injection channels using Zeiss AxioVision ® and Microsoft Excel ® software. For the proof of concept, intracerebral stereotactic surgery was performed in 50-day-old APP-transgenic mice injected with PBS. At the age of 100 days, brains were collected for immunhistological analysis. Results: The toolbox can be used to analyze and evaluate Aβ plaques (number, size, and coverage) in specific brain areas based on their location relative to the point of the injection or the injection channel. The tool provides classification of Aβ plaques in pre-defined distance groups using two different approaches. Conclusion: This new analytic toolbox facilitates the analysis of long-term continuous intracerebral experimental compound infusions using ALZET ® pumps. This method generates reliable data for Aβ deposition characterization in relation to the distribution of experimental compounds.

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“…To our knowledge, this is the first in vivo study to examine the effect of the naturally occurring antioxidant PQQ on denervation-induced skeletal muscle atrophy. Continuous and regular administration of PQQ was achieved using an ALZET® osmotic pump, which has proven to be an extremely useful tool for the long-term, continuous delivery of compounds for research purposes [ 27 , 28 ]. We examined the gastrocnemius rather than the soleus muscle, as almost half of the gastrocnemius muscle quickly wasted away 10 days post denervation [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Pyrroloquinoline Quinone Resists Denervation-Induced Skeletal Muscle Atrophy by Activating PGC-1α and Integrating Mitochondrial Electron Transport Chain Complexes

et al. 2015

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Denervation-mediated skeletal muscle atrophy results from the loss of electric stimulation and leads to protein degradation, which is critically regulated by the well-confirmed transcriptional co-activator peroxisome proliferator co-activator 1 alpha (PGC-1α). No adequate treatments of muscle wasting are available. Pyrroloquinoline quinone (PQQ), a naturally occurring antioxidant component with multiple functions including mitochondrial modulation, demonstrates the ability to protect against muscle dysfunction. However, it remains unclear whether PQQ enhances PGC-1α activation and resists skeletal muscle atrophy in mice subjected to a denervation operation. This work investigates the expression of PGC-1α and mitochondrial function in the skeletal muscle of denervated mice administered PQQ. The C57BL6/J mouse was subjected to a hindlimb sciatic axotomy. A PQQ-containing ALZET® osmotic pump (equivalent to 4.5 mg/day/kg b.w.) was implanted subcutaneously into the right lower abdomen of the mouse. In the time course study, the mouse was sacrificed and the gastrocnemius muscle was prepared for further myopathological staining, energy metabolism analysis, western blotting, and real-time quantitative PCR studies. We observed that PQQ administration abolished the denervation-induced decrease in muscle mass and reduced mitochondrial activities, as evidenced by the reduced fiber size and the decreased expression of cytochrome c oxidase and NADH-tetrazolium reductase. Bioenergetic analysis demonstrated that PQQ reprogrammed the denervation-induced increase in the mitochondrial oxygen consumption rate (OCR) and led to an increase in the extracellular acidification rate (ECAR), a measurement of the glycolytic metabolism. The protein levels of PGC-1α and the electron transport chain (ETC) complexes were also increased by treatment with PQQ. Furthermore, PQQ administration highly enhanced the expression of oxidative fibers and maintained the type II glycolytic fibers. This pre-clinical in vivo study suggests that PQQ may provide a potent therapeutic benefit for the treatment of denervation-induced atrophy by activating PGC-1α and maintaining the mitochondrial ETC complex in skeletal muscles.

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Development of ALZET® osmotic pump compatible solvent compositions to solubilize poorly soluble compounds for preclinical studies

Cited by 17 publications

References 19 publications

Frontline Science: Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1β activation

Frontline Science: Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1β activation

A New Tool for the Analysis of the Effect of Intracerebrally Injected Anti-Amyloid-β Compounds

Pyrroloquinoline Quinone Resists Denervation-Induced Skeletal Muscle Atrophy by Activating PGC-1α and Integrating Mitochondrial Electron Transport Chain Complexes

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