Microspheres targeting

Coatings for inertial confinement microsphere targets comprised of multilayers of Be, Au, Pt, and Ta.P l... 

Eldridge, J.H., Hammond, C.J., Meulbroek, J.H., Staas, J.K., Gilley, R.M., and Tice, T.R. (1990). Controlled vaccine release in the gut-associated lymphoid tissues. I. Orally administrated biodegradable microspheres target the Peyer s patches. J. Control. Release, 11, 205-214. 

In view of these potential advantages, the process of plasma polymerization was adapted to coat microsphere targets. A special device for exposing the microspheres to obtain a uniform coating was devised. A major problem which was solved was the elimination of rough surfaces characteristic of these coatings. 

Jepson, M.A., Simmons, N.L., Hagan, D.T.O., Hirst, B.H. Comparison of poly(DL-lactide-co-glycolide) and polystyrene microsphere targeting to intestinal M cells. J. Drug Target., 1, 245, 1993. 

Richards AL, Kleinstreuer C, Kennedy AS, Childress E, Buckner GD (2012) Experimental microsphere targeting in a representative hepatic artery system. IEEE Trans Biomed Eng 59 198-204... 

Controlled vaccine release in the gut-associated lymphoid tissues. 1. Orally administered biodegradable microspheres target the Peyer s patches, J. Controlled Release 11 205-214. 

The development of injectable mictocapsules for deUvery of chemotherapy agents remains another active area of research. The ultimate goal is to achieve targeted deUvery of chemotherapy agents to specific sites in the body, ideaUy by injection of dmg-loaded mictocapsules that would seek out and destroy diseased ceUs. Intra-arterial infusion chemotherapy is a direct approach to targeted deUvery. The clinical appHcations of microspheres and mictocapsules in embolization and chemotherapy have been assessed (49) (see Chemotherapeutics, anticancer). 

Poly(DL-lactide) was used as the excipient in microspheres of CCNU, a nitrosourea, prepared by a solvent evaporation procedure (96,97). PLA-CCNU microspheres 3.0 pm in diameter were injected i.v. and leukemia cell survival was determined by spleen colony assay. A 100-fold decrease in leukemia cell survival was observed with the microspheres in both spleen and liver compared to untreated controls. Promising results were also obtained with Lewis lung carcinoma in mice. These studies showed that 2- to 4-ym microspheres were preferentially targeted to the lungs. 

Target tissue sections from animals sacrificed at 8 hr and later after dosing showed the presence of microspheres in the extravas-cular interstitial tissue. Changes in red blood cells and damage to other cellular components suggest that the cytotoxic properties of adriamycin have been retained. The microspheres appeared to still be intact for up to 72 hr. 

As was the case with albumin, reports on clinical studies employing gelatin microspheres are limited and confined to Japan. Bleomycin, contained in a microsphere-in-oil formulation, was targeted to the lymph nodes for the treatment of infantile cystic hygroma, a benign tumor (143). Successful treatment was noted in all cases. 

Chen et al. (163) targeted magnetic microspheres containing 5-fluorouracil to the esophagus by application of an external magnet. 

Direct observation of molecular diffusion is the most powerful approach to evaluate the bilayer fluidity and molecular diffusivity. Recent advances in optics and CCD devices enable us to detect and track the diffusive motion of a single molecule with an optical microscope. Usually, a fluorescent dye, gold nanoparticle, or fluorescent microsphere is used to label the target molecule in order to visualize it in the microscope [31-33]. By tracking the diffusive motion of the labeled-molecule in an artificial lipid bilayer, random Brownian motion was clearly observed (Figure 13.3) [31]. As already mentioned, the artificial lipid bilayer can be treated as a two-dimensional fluid. Thus, an analysis for a two-dimensional random walk can be applied. Each trajectory observed on the microscope is then numerically analyzed by a simple relationship between the displacement, r, and time interval, T,... 

AFJr Yapel. Albumin microspheres heat and chemical stabilization. In KJ Widder, R Green, eds. Methods in Enzymology Part A, Drug and Enzyme Targeting. Orlando Academic Press, 1985, pp 3-18. 

K. J. Widder and A. E. Senyei, Magnetic microsphere A vehicle for selective targeting of organs, in Methods of Drug Delivery (G. M. Ihler, ed.), Pergamon Press, New York, 1986, p. 39. 

Toll, R., Jacobi, U., Richter, H., Lademann, J., Schaefer, H., and Blume-Peytavi, U. (2004) Penetration profile of microspheres in follicular targeting of terminal hair follicles. Journal of Investigative Dermatology, 123 (1), 168-176. 

Monodisperse microspheres imprinted with theophylline or 17 (3-estradiol were used in competitive radioimmunoassays showing the MIP s high selectivity for the template molecule. In this case the assay is based on the competition of the target molecule with its radioactively labeled analogue for a limited number of antibody binding sites [77,118]. Figure 15 demonstrates that displacing the radioactively marked theophylline from the imprinted polymer was only possible with theophylline as competitor. Structurally related molecules showed effects solely at elevated concentrations [77]. 

Widder KJ, Marino PA, Morris RM, Howard DP, Poore GA, Senyei AE (1983a) Selective targeting of magnetic albumin microspheres to the Yoshida sarcoma ultrastructural evaluation of microsphere disposition. Eur J Cancer Clin Oncol 19 141-147. 

Several types of dmg carriers such as microspheres, liposomes, and polymer have been investigated to achieve targetable drug delivery, especially for anticancer drugs. However, nonselective scavenging of such carriers by the reticuloendothelial system (RES) is a serious problem even when monoclonal antibodies are used to carry the dmg [15,16]. 

Fig. 12 a Quenching assay where QSY-7-labeled DNA strand (DNA-QTL) is presented to microsphere and microsphere-bound biotinylated ALF capture strand, b Competition assay for detection of target DNA. Variable amounts of ALF target are added to microsphere and bound ALF capture strand. This is then subjected to a fixed amount of QSY-7-labeled DNA. The amount of quenching is dependent on the amount of ALF target already bound on the microsphere. (Reprinted with permission from Ref. [33]. Copyright 2002 American Chemical Society)... 

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