Slow release of anticancer drugs from porous calcium hydroxyapatite ceramic

Abstract

We have developed a new delivery system for sustained release of an anticancer drug (cis-platinum) by enclosure into blocks of porous calcium hydroxyapatite ceramic. The slow release of this drug from this system was confirmed in in vitro experiments. When this system was implanted into normal back muscle, or the tibia, sustained release of cis-platinum was observed during a 12-week period after implantation. The diffusion rate of cis-platinum into blood and other organs (liver, kidney, brain) was less than 10% of that at the implanted site. This delivery system placed into experimental tumors of mice also showed a uniform release of anticancer drug for more than 3 months. Inhibition of tumor growth was more marked after local implantation of this system than after intraperitoneal administration of cis-platinum. These results indicate that this new approach to a drug delivery system may well have an important role in cancer chemotherapy. In bone tumors it is attractive because the mechanical strength of calcium hydroxyapatite ceramic permits partial surgical excision and replacement of the bone defect at the same time.

Hydroxyapatite crystals as a local delivery system for cisplatin: adsorption and release of cisplatin in vitro

“…4). Previous experiments with cisplatin showed that more than 90% of cisplatin that was originally enclosed into blocks of a porous ceramic of hydroxyapatite was released over a three-month period in PBS [37]. Other studies of cisplatin binding to a calcium phosphate cement which contained 10% and 20% of cisplatin (by weight), respectively, were shown to release about 30% and 60%) of cisplatin after four weeks of equilibration [36].…”

“…Many studies utilizing hydroxyapatite or tricalcium phosphate ceramics have demonstrated that such complexes can be used to deliver steroids [lo], antibiotics [20,34], proteins [3,4], hormones [IS], anticancer drugs [32,36,37] anticoagulants [1,27] and azidothymidine [9,13]. However, very little is known about the factors regulating the binding and release of specific chemical compounds in vitro.…”

Interactions of cisplatin with calcium phosphate nanoparticles: In vitro controlled adsorption and release

“…Cis-diamminedichloroplatinum (cisplatin) is one of the most active anti-cancer agents in the treatment of osteosarcoma, but must be used in limited short-term, high-dose treatments because of nephrotoxicity and ototoxicity. The minimization of the systemic toxicity of chemotherapeutic drugs including cisplatin has been demonstrated after local intratumoral treatments with comparable anti-tumor efficacy to that of a systemic dose [2,8,10,13,14,16,[22][23][24]. Calcium phosphate (CaP) blocks with embedded cisplatin in the solid form, apatite cement containing embedded cisplatin, and CaP powders compacted with chemotherapy have been implanted adjacent to tumors in animal models and indicate that local delivery of cisplatin from hydroxyapatite (HA) can result in tumor inhibition and much lower, less-toxic systemic values of released drug [13,16,23,24].…”

“…The minimization of the systemic toxicity of chemotherapeutic drugs including cisplatin has been demonstrated after local intratumoral treatments with comparable anti-tumor efficacy to that of a systemic dose [2,8,10,13,14,16,[22][23][24]. Calcium phosphate (CaP) blocks with embedded cisplatin in the solid form, apatite cement containing embedded cisplatin, and CaP powders compacted with chemotherapy have been implanted adjacent to tumors in animal models and indicate that local delivery of cisplatin from hydroxyapatite (HA) can result in tumor inhibition and much lower, less-toxic systemic values of released drug [13,16,23,24]. As pointed out by Barroug and Glimcher [3], in this type of solid within a solid formulation, the passage of the drug from the solid CaP device into the surrounding tissue is a complex function of solubilization of the drug, adsorption to the CaP device, and diffusional gradients.…”

Immobilization of Chinese herbal medicine onto the surface-modified calcium hydrogenphosphate

“…It is expected to promote bone tissue to growth and differentiation through effective biodegradation delivery system. Calcium phosphate ceramics have been used as drug carriers and delivery systems for numerous drugs: bisphosphonates [12], chlorhexidine [13], antibiotics [14][15][16][17], insulin [18], aspirin [19], hormones [20], coumadin [21], anticancer drugs [22][23], indomethacin [24], epinephrine [25], and azidothymidine [26]. Calcium phosphate ceramics loaded with bone growth factors are of interest for developing biomaterials.…”