Porous nano-hydroxyapatite/collagen scaffold containing drug-loaded ADM–PLGA microspheres for bone cancer treatment

Abstract

To develop adriamycin (ADM)-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles in a porous nano-hydroxyapatite/collagen scaffold (ADM-PLGA-NHAC). To provide novel strategies for future treatment of osteosarcoma, the properties of the scaffold, including its in vitro extended-release properties, the inhibition effects of ADM-PLGA-NHAC on the osteosarcoma MG63 cells, and its bone repair capacity, were investigated in vivo and in vitro. The PLGA copolymer was utilized as a drug carrier to deliver ADM-PLGA nanoparticles (ADM-PLGA-NP). Porous nano-hydroxyapatite and collagen were used to materials to produce the porous nano-hydroxyapatite/collagen scaffold (NHAC), into which the ADM-PLGA-NP was loaded. The performance of the drug-carrying scaffold was assessed using multiple techniques, including scanning electron microscopy and in vitro extended release. The antineoplastic activities of scaffold extracts on the human osteosarcoma MG63 cell line were evaluated in vitro using the cell counting kit-8 (CCK8) method and live-dead cell staining. The bone repair ability of the scaffold was assessed based on the establishment of a femoral condyle defect model in rabbits. ADM-PLGA-NHAC and NHAC were implanted into the rat muscle bag for immune response experiments. A tumor-bearing nude mice model was created, and the TUNEL and HE staining results were observed under optical microscopy to evaluate the antineoplastic activity and toxic side effects of the scaffold. The composite scaffold demonstrated extraordinary extended-release properties, and its extracts also exhibited significant inhibition of the growth of osteosarcoma MG63 cells. In the bone repair experiment, no significant difference was observed between ADM-PLGA-NHAC and NHAC by itself. In the immune response experiments, ADM-PLGA-NHAC exhibited remarkable biocompatibility. The in vivo antitumor experiment revealed that the implantation of ADM-PLGA-NHAC in the tumor resulted in a improved antineoplastic effect and fewer adverse side effects than direct intraperitoneal injection of ADM. The ADM-PLGA-NHAC developed in this study exhibited excellent extended-release drug properties, bone repairing and antineoplastic efficacy, which make it a promising osteoconductivity material with the capability to inhibit osteosarcoma.

Sustained curcumin release from PLGA microspheres improves bone formation under diabetic conditions by inhibiting the reactive oxygen species production

“…Over the last decades, composite materials made from hydroxyapatite and collagen have attracted a great deal of attention for their good biocompatibility and excellent ability of promoting bone regeneration. 21 , 22 Currently, most of the collagen materials used for fabricating bone grafts are extracted from mammals, such as cattle, pigs, and rats. However, the use of mammalian-derived collagen may transmit zoonotic diseases, such as bovine spongiform encephalopathy and foot-and-mouth disease, and is limited by religious affiliation.…”

Hydroxyapatite–polymer biocomposites for bone regeneration: A review of current trends

“…Upon degradation PLGA breaks down into lactic acid and glycolic acid which are the usual by‐products of human metabolism and can be excreted by urine . Apart from drug delivery where it is mainly used, PLGA systems are used in the areas such as bone, skin, cartilage, and nerve regeneration …”

Toxic effect of cadmium adsorbed by different sizes of nano-hydroxyapatite on the growth of rice seedlings

“…As a water-stable and biocompatible nano-material (Huang and Wang, 2007), nano-hydroxyapatite (NHAP) is widely used for medicinal purposes (Rong et al, 2016). NHAP has been increasingly used as a nano-adsorbent to remediate Cd contamination in aqueous and soil environments owing to its remarkable adsorption capacity for HMIs (Jin et al, 2016;Wang et al, 2016).…”