Microspheres therapeutic applications

Chappell JC, Price RJ. Targeted therapeutic applications of acoustically active microspheres in the microcirculation. Microcirculation 2006 13 57-70. 

Fig. 8.1, Safety assessment prior to SIR-Spheres therapy. Scintigraphy with macroaggregated albumin (MAA) acquired after intraarterial administration of MAA during hepatic angiography shows extrahepatic deposition of particles. A therapeutic application of microspheres under the same conditions would have resulted in severe complications...

A fundamental understanding of the in-vivo biodegradation phenomenon of biodegradable polymeric microspheres is one of the important components in the design and development of biodegradable microspheres containing bioactive agents for therapeutic application [3]. 

Figures 4, 5 and 13 show the release of proteins form macroscopic dextran-based hydrogels. For therapeutic applications of these protein-loaded gels, injectable dosage forms like microspheres are preferred. Extensive research has been done so far on the preparation of microspheres based on biodegradable polymers (e.g. PLGA). However, for the preparation of these microspheres, organic solvents are used which might cause denaturation of the encapsulated protein (see Introduction). Furthermore, the use of organic solvents has environmental and clinical drawbacks.

Shunmugaperumal Tamilvanan, University of Antwerp, Antwerp, Belgium, Progress in Design of Biodegradable Polymer-Based Microspheres for Parenteral Controlled Delivery of Therapeutic Peptide/Protein Oil-in-Water Nanosized Emulsions Medical Applications... 

A major challenge is the limited dose concentration of microspheres due to drugloading constraints. Dispersions are un-Hkely to contain more than 15% (m/m) particles that usually provide a maximum drag load of less than 20%. Considering an injection volume of 1-2 mL, not more than 60 mg drag substance can be appHed. This is not a concern for low drag dose indications such as growth factors [64, 65, 78] or vaccines [79], but it may be an obstacle for the application of other therapeutic peptides. 

The observed data indicate the wide prospects in applications of drug-loaded medical devices and microspheres on the base of PHB as implantable and injectable therapeutic systems in medicine for treatment of various diseases cancer, cardiovascular diseases, tuberculosis, osteomyelitis, arthritis, and so on [6]. 

Currently, a variety of imaging procedures are available to help detect and confirm liver metastases of extrahepatic tumors or primary hepatic tumors. The therapeutic effects of microsphere distribution, however, are not necessarily directly related to structural changes or metabolic abnormalities of the cells as detected with these imaging methods. Owing to the selective application of SIR-Spheres into the hepatic artery, the distribution of microspheres within the liver is primarily determined by hemodynamic aspects such as increased arterial perfusion of the liver metastases and low arteriovenous shunting [30]. 

Slow application of SIR-Spheres will also result in predominant flow into large vessels at first. As these become occluded, however, the flow profile changes and the microspheres follow the changed blood flow into different vessel branches. Conceivably, this may limit the accuracy of MAA scintigraphy in predicting therapeutic SIR-Spheres distribution. 

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