Collagen-hydroxyapatite/Cisplatin Drug Delivery Systems for Locoregional Treatment of Bone Cancer

Abstract

In this paper, the synthesis and characterization of novel cisplatin-loaded collagen (COLL)/hydroxyapatite (HA) composite materials are presented. The composite materials were designed to obtain a COLL: HA weight ratio close to the bone composition. The content of embedded cisplatin was chosen to assure a concentration of cisplatin of 6 and 10 μM, respectively, into the culture media used in cell culture experiments. These cisplatin delivery systems were characterized by determining the physico-chemical properties of the composite material, the drug release process as well as their biological activity. Based on the in vitro data that showed the cytotoxic, anti-proliferative and anti-invasive activities of these multifunctional systems on G292 osteosarcoma cells in dependence on the cisplatin concentration released in culture medium, we conclude that the newly developed COLL/HA-cisplatin drug delivery system could be a feasible approach for locoregional chemotherapy of bone cancer.

Multifunctional materials for bone cancer treatment

“…77 It is worth mentioning that type I collagen is also com mercially available and used as wound dressing, especially in the case of burns, 83,84 as a main component of many creams designed for care or treatment of skin laxity, rhytides, or photoaging, 85 or as a component of many engineered materi als used for bone regeneration and cancer treatment. 70,78,86,87 Collagen has also been used since 1980 as a drugdelivery system for ophthalmic agents (especially the antibiotics gentamicin and vancomycin), 88 the trend being to extend the use of this material in obtaining many other drugdelivery systems. 71,78,89 Despite intensive research efforts in the field of bone and bone grafts, 29,[90][91][92][93][94] the properties of the materials obtained are still far from those of healthy bone.…”

“…Bone fillers can in fact be more complex systems incorporating pharmaceutically active substances (analgesic and/or antitumoral drugs), allowing them to be released in situ. 70,134 Generally, the presented multifunctional systems were developed in order to assist natural repair mechanisms (bone morphogenic protein presence improves the rate of bone regeneration, bisphosphonate indirectly favors bone formation by suppressing bone resorption) or even to act as All these systems can be assimilated with drugdelivery systems and could be used to treat diseases from simple bone defects/fractures up to bone cancer. It is expected that clini cal trials will be positive, because local administration will improve drug efficiency and limit side effects.…”

“…Starting from the wellestablished materials for bone grafting, different kinds of natural or synthetic components (Table 3) 70 or even more complex systems. 134 A main functionality of many of these systems is related to their ability to deliver the active component.…”

“…70 Apatitebased materials are extensively used as bone filler/ grafts. [148][149][150] This is why many drugdelivery systems designed for bonedisease treatment are based on hydroxyapatite.…”

“…[56][57][58][59][60][61][62][63][64][65][66][67] Also, proteins (collagen being the most abundant) are known as support for drugdelivery systems, but usually their high chemical and physical instability present technical problems related to synthesis and storage. [68][69][70][71] PVA is extremely useful for chemoembolization, and in certain conditions can be loaded with various antitumoral drugs, such as cisplatin, doxorubi cin, mitomycin C, and ethiodol. 67,[72][73][74] Ceramic drugdelivery systems are also used for the treatment of bone cancer.…”