The targeted delivery of anti-cancer drugs and isotopes is one of the most pursued goals in anti-cancer therapy. One of the prime examples of such an application is the intra-arterial injection of microspheres containing cytostatic drugs or radioisotopes during hepatic embolization procedures. Therapy based on the application of microspheres revolves around vascular occlusion, complemented with local therapy in the form of trans-arterial chemoembolization (TACE) or radioembolization (TARE).
Property | Importance |
---|---|
Specific gravity (particle density) | Dispersion in other media or occlusion of the micro-vasculature |
Size | Particle size (diameter = 50–750 mm) that allows occlusion of the microvasculature |
Durability | Strength during production, solvent resistance, sterilization, chemical stability, or biodegradation, the release of the therapeutical payload |
Biocompatibility | Safety, toxicity, stability, suitable for intra-arterial delivery |
Pharmacology | Controlled dosimetry and dosing, full control over release profile by diffusion, zero-order kinetics |
Surface properties | Hydrophobic vs. hydrophilic surface, surface area, and porosity, ability to coat or functionalize the spheres |
Microspheres Composition | Product Name | Particle Size Range (⌀ μm) | PC/H (FDA Clearance) | Biodegradable | References | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Tris acryl gelatin microspheres (TAGM) | Embosphere | ® | (Merit Medical Systems, South Jordan, UT, USA) | 100–300, 300–500 | H (FDA) | No | [24] | ||||
Polyvinyl alcohol (PVA) sodium acrylate co-polymer microspheres | Contour SE | ® | (Boston Scientific, Marlborough, MA, USA), Bead Block | ® | (Boston Scientific, Marlborough, MA, USA) Embozene | ® | (Varian Medical Systems, Palo Alto, CA, USA) | Irregular: 150–250, 250–355, 355–500, 500–710 |
H (FDA) | No | [25] |
Polyvinyl alcohol-based hydrogel microspheres with sulphonate groups | LC Bead | ® | (Boston Scientific, Marlborough, MA, USA) | 75–150, 100–300, 300–500, 500–700 | H (FDA) | No | [26,27,28,29] | [26][27][28][29] | |||
Co-polymer of PEG and diacrylamide | Hydropearl | ® | (Terumo Medical Co., Somerset, NJ, USA) | 75–1100 | H (FDA) | No | Mitomycin, doxorubicin, irinotecan, sunitinib, cisplatin[1] | ||||
Starch microspheres | Embocept | ® | (Pharmacept, Berlin, Germany), Spherex | ® | (Magle Life Sciences, Lund, Sweden) | 50 | PC | Yes | [1] | ||
Gelatin microspheres | Gel-Bead (Teleflex, Morrisville, NC, USA) | 100–300, 300–500, 500–700, 7000–1000 | H (FDA) | Yes | [1] | ||||||
Collagen-coated poly-(DL-lactic acid-co-glycolic acid (PLGA) microspheres | Occlusin500 | ® | (IMBiotechnologies, Edmonton, AL, Canada) | 150–210 | H | Yes | [1] |
Microspheres Composition |
Product Name | Particle Size Range (⌀ µm) | Radioisotope Load | Pre-Clinical/ Human Use (FDA Clearance) |
Biodegradable | References | ||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Polyvinyl alcohol (PVA) sodium acrylate co-polymer microspheres | QuadraSphere | ® | and HepaSphere™ (Merit Medical Systems, Inc., South Jordan, UT, USA) DC Bead | ® | (Boston Scientific, Marlborough, MA, USA), | |||||||||||||||||||||||||||||||||||||||||||||
Glass | LC Bead | ® | , and Bead Block | ® | (Boston Scientific, Marlborough, MA, USA) | Lipiocis, TheraSphere | ® | 50–100, 100–300, 200–400 | (Boston Scientific, Marlborough, MA, USA) | 50–150, 20–30, 25–32Doxorubicin, irinotecan, epirubicin, oxaliplatin | 32 | P, PC/H (FDA) | 90 | Y, | 177 | No | lu, | 186 | Re, | 188 | Re | PC/H (FDA for | 90 | Y, | 186 | Re, and | 188 | Re) | [14,26,32, | [ | 33,34, | 14 | 35, | No | [60,] | [60] | 61, | [61] | 36] | ][26][32] | 62 | [33 | , | [] | 63 | [34][ | ,64, | 62][63][64]35] | 65 | [[36] |
65 | ] | Ion-exchange microspheres | CalliSpheres | ® | Beads (Jiangsu Hengrui Medicine Co. Ltd. Jiangsu, China) | 100–300 | Doxorubicin, pirarubicin, oxaliplatin | PC/H | No | [37 | ||||||||||||||||||||||||||||||||||||||||
Resin | SIR-Spheres | ® | (Sirtex Medical Inc. Woburn, MA, USA), Amberlite IR-120 (Thermo Fisher Scientific, Landau, Germany) |
20–60 | 90 | Y, | 153 | Sm | PC/H (FDA for | 90 | Y) | ,38,39,40,41] | [37][38][39][40][41] | |||||||||||||||||||||||||||||||||||||
No | [ | 66 | , | 67 | , | 68,69] | [66][67][68][69] | Tris acryl gelatin microspheres (TAGM) | Embosphere (Merit Medical Systems, South Jor-dan, UT, USA), Embozene | ® | , and Oncozene™ (Varian Medical Systems, Palo Alto, CA, USA) | 40–120, 100–300 | Doxorubicin and Irinotecan | H (FDA) | No | |||||||||||||||||||||||||||||||||||
Polyhydroxyamic acid polyacrylamide (PHA) | [ | 13 | , | 36 | , | 42, | Experimental | 43] | [13][36][42][43] | |||||||||||||||||||||||||||||||||||||||||
54 | 177 | lu, | 131 | I | PC | No | [70,71,72] | [70][71][72] | Poly-lactide-co-glycolide (PLGA) | Dexon | ® | , Vicryl | ® | , Perseris | TM | , Indivior (Indivior Inc. North Chesterfiled, VI, USA), Risperdal Consta | ® | 20–100 | ||||||||||||||||||||||||||||||||
Styrene divinylbenzene | Amberlite IR-120 (Thermo Fisher Scientific, Landau, Germany) | 20–40 | 152 | Sm | PC | No | [69,73] | [69][73] | ||||||||||||||||||||||||||||||||||||||||||
Poly- DL-lactic acid-co-glycolic acid (PLGA) | YPO | 4 | crystalline particles Radiogel | ® | (Vivos Inc., Richland, WA, USA) | 0.5–2 | 90 | Y | PC (FDA-approved as a medical device) | Yes | [74] | |||||||||||||||||||||||||||||||||||||||
Poly (L-lactic acid) PLLA | Resomer | ® | L104 (Merck, Darmstad, Germany) | 10–45, 20–40 | 188 | Re/ | 166 | Ho/ | 175 | Yb | PC/C | Yes | [75,76,77,78,79,80,81] | [75][76][77][78][79][80][81] | ||||||||||||||||||||||||||||||||||||
Poly (glycidyl methacrylate- | co | -ethylene dimethacrylate & Quinoline-8-ol | G-Gel (Merck, Darmstad, Germany) | 20–40 | 131 | I, | 177 | lu | PC | No | [66,70,71,72,82] | [66][70][71][72][82] | ||||||||||||||||||||||||||||||||||||||
Hydroxyapatite | QuiremSpheres (Quirem Medical, Deventer, The Netherlands) |
20–60 | 166 | Ho | PC | No | [78,83,84] | [78][83][84] | ||||||||||||||||||||||||||||||||||||||||||
Albumin | HSA-B20 (Rotop Pharmaka, Dresden, Germany) Vasculosis | ® | (Global Medical Solutions, Auckland, New Zealand) MAA (DRAXIMAGE | ® | , Kirkland, QC, Canada), Pulmocis | ® | (Curium, London, UK) | 25–35, 15–37 | 90 | Y, | 186 | Re, | 188 | Re | PC/C | Yes | [63,64,65,85,86,87] | [63][64][65][85][86][87] | ||||||||||||||||||||||||||||||||
Chitosan | Millican (Dong Wha Pharmaceutical Co., Soeul, South Korea) | 5–20 | 166 | Ho | PC/C | Yes | [75,76, | 75 | 77,78, | ][76 | 79, | ][77 | 88, | ] | 89,90] | [[78][79][88][89][90] | ||||||||||||||||||||||||||||||||||
Starch-based microparticles (SBMP) | Experimental Kit | 18–42 | 188 | Re | PC | No | [91,92,93] | [91][92][93] |