[1] Albumin microspheres: Heat and chemical stabilization

Yapel, Anthony F.

doi:10.1016/s0076-6879(85)12003-3

Cited by 37 publications

(18 citation statements)

References 8 publications

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“…In the current studies, we examine MPs from the other extreme – very flexible particles. Interestingly, IV injected rigid particulates (size <4 μm) pass through the lung and become entrapped by macrophages of the reticuloendothelial system with the majority found in the liver, and the remainder in the spleen and bone marrow [35–37]. Smaller particles (5.5–30 nm) tend to accumulate in a relatively higher concentration in bone-marrow [38].…”

Section: Resultsmentioning

confidence: 99%

Biodistribution and renal clearance of biocompatible lung targeted poly(ethylene glycol) (PEG) nanogel aggregates

Deshmukh

Kutscher

Gao

et al. 2012

Journal of Controlled Release

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A novel stabilized aggregated nanogel particle (SANP) drug delivery system was prepared for injectable passive lung targeting. Gel nanoparticles (GNPs) were synthesized by irreversibly cross-linking 8 Arm PEG thiol with 1,6-Hexane-bis-vinylsulfone (HBVS) in phosphate buffer (PB, pH 7.4) containing 0.1% v/v Tween™ 80. Aggregated nanogel particles (ANPs) were generated by aggregating GNPs to micron-size, which were then stabilized (i.e., SANPs) using a PEG thiol polymer to prevent further growth-aggregation. The size of SANPs, ANPs and GNPs was analyzed using a Coulter counter and transmission electron microscopy (TEM). Stability studies of SANPs were performed at 37 °C in rat plasma, phosphate buffered saline (PBS, pH 7.4) and PB (pH 7.4). SANPs were stable in rat plasma, PBS and PB over 7 days. SANPs were covalently labeled with HiLyteFluor™750 (DYE-SANPs) to facilitate ex vivo imaging. Biodistribution of intravenous DYE-SANPs (30 μm, 4 mg in 500 μL PBS) in male Sprague-Dawley rats was compared to free HiLyteFluor™750 DYE alone (1 mg in 500 μL PBS) and determined using a Xenogen IVIS®100 Imaging System. Biodistribution studies demonstrated that free DYE was rapidly eliminated from the body by renal filtration, whereas DYE-SANPs accumulated in the lung within 30 minutes and persisted for 48 h. DYE-SANPs were enzymatically degraded to their original principle components (i.e., DYE-PEG-thiol and PEG-VS polymer) and were then eliminated from the body by renal filtration. Histological evaluation using H & E staining and broncho alveolar lavage (BAL) confirmed that these flexible SANPs were not toxic. This suggests that because of their flexible and non-toxic nature, SANPs may be a useful alternative for treating pulmonary diseases such as asthma, pneumonia, tuberculosis and disseminated lung cancer.

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Section: Resultsmentioning

confidence: 99%

Biodistribution and renal clearance of biocompatible lung targeted poly(ethylene glycol) (PEG) nanogel aggregates

Deshmukh

Kutscher

Gao

et al. 2012

Journal of Controlled Release

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“…They are 50% biodegraded and solubilized in body fluids in the times shown as judged by histological techniques. Reprinted from Yapel [1985], by permission of Elsevier Science.…”

Section: Sterilizationmentioning

confidence: 99%

Biopolymer albumin for diagnosis and in drug delivery

Patil¹

2003

Drug Development Research

156

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This article reviews the developmental stages and strategies used to assess the biomedical utility of biopolymer albumin from the 1970s to early 2002. The basic method and mechanism(s) of preparation of albumin microspheres and subsequent modifications made to overcome the drawbacks of earlier approaches and the need for further developments are discussed, as are the processing parameters and the level of various ingredients affecting the physicochemical properties of the albumin microspheres. Different equations proposed by various investigators to modulate in vitro release kinetics are reviewed. The microscopic structural and surface properties, the chemical modification of the biopolymer (e.g., cationization, tagging with amino acids and sugar moieties) for tissue specificity or to influence the release profile and biodegradation are discussed. An array of potential diagnostic applications and the use of albumin microspheres as a drug delivery system are reviewed. Drug Dev.

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“…Most recent studies have focused on rigid MPs. Several studies have found that smaller rigid particulates (<4 μm) pass through the lung and become entrapped in the reticuloendothelial system (RES) whereas the vast majority (80-90%) are found in the liver with the remainder in the spleen (5-8%) and bone marrow (1-2%) [24, 27-29]. Larger particulates (>10 μm) became entrapped in the lung.…”

Section: Introductionmentioning

confidence: 99%

Threshold size for optimal passive pulmonary targeting and retention of rigid microparticles in rats

Kutscher

Chao

Deshmukh

et al. 2010

Journal of Controlled Release

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The relationship between microparticle (MP) size and lung targeting efficiency, intra-lung distribution and retention time was systematically studied after intravenous administration of rigid fluorescent polystyrene MPs of various sizes (2, 3, 6 and 10μm) to Sprague-Dawley rats. Total fluorescence was assessed and it was found that 2μm and 3μm MPs readily passed through the lung to the liver and spleen while 10μm MPs were completely entrapped in the lung for the one-week duration of the study. Approximately 84% of 6μm MPs that were initially entrapped in the lung were cleared over the next 2 days and 15% were cleared over the remaining 5 days. A Caliper IVIS® 100 small animal imaging system confirmed that 3μm MPs were not retained in the lung but that 6μm and 10μm MPs were widely distributed throughout the lung. Moreover, histologic examination showed MP entrapment in capillaries but not arterioles. These studies suggest that for rigid MPs the optimal size range required to achieve transient but highly efficiently targeting to pulmonary capillaries after IV injection is >6μm but <10μm in rats and that systemic administration of optimally sized MPs may be an efficient alternative to currently used inhalation-based delivery to the lung. KeywordsPassive pulmonary targeting; Rigid non-biodegradable microparticle; In vivo imaging

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[1] Albumin microspheres: Heat and chemical stabilization

Cited by 37 publications

References 8 publications

Biodistribution and renal clearance of biocompatible lung targeted poly(ethylene glycol) (PEG) nanogel aggregates

Biodistribution and renal clearance of biocompatible lung targeted poly(ethylene glycol) (PEG) nanogel aggregates

Biopolymer albumin for diagnosis and in drug delivery

Threshold size for optimal passive pulmonary targeting and retention of rigid microparticles in rats

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