This study developed a novel bioactive bone substitute (hydroxyapatite, HA) with improved anti-biofilm activity by functionalizing with curcumin (anti-biofilm compound) which provide sufficient flux of curcumin concentration for 14 days. The released curcumin acts to inhibit biofilm formation and control the number of viable planktonic cells simultaneously. To prepare curcumin-functionalized HA, different concentrations of curcumin (up to 3% w/v) were added simultaneously during the precipitation process of HA. The highest loading (50 mg/g HA) of curcumin onto HA was achieved with 2% w/v of curcumin. Physicochemical characterizations of curcumin-functionalized HA composites revealed that curcumin was successfully incorporated onto HA. Curcumin was sustainably released over 14 days, while higher curcumin release was observed in acidic condition (pH 4.4) compared to physiological (pH 7.4). The cytotoxicity assays revealed that no significant difference on bone cells growth on curcumin-functionalized HA and non-functionalized HA. Curcumin-functionalized HA was effective to inhibit bacterial cell attachment and subsequent biofilm maturation stages. The anti-biofilm effect was stronger against Staphylococcus aureus compared to Pseudomonas aeruginosa. The curcumin-functionalized HA composite significantly delayed the maturation of S. aureus compared to non-functionalized HA in which microcolonies of cells only begin to appear at 96 h. Up to 3.0 log reduction in colony forming unit (CFU)/mL of planktonic cells was noted at 24 h of incubation for both microorganisms. Thus, in this study we have suggested that curcumin loaded HA could be an alternative antimicrobial agent to control the risk of infections in post-surgical implants.
This study has evaluated the effect of functionalizing surface charges of hydroxyapatite on the modulation of loading and release of curcumin nanoparticles. The increase in loading and release of curcumin nanoparticles indirectly translates to enhanced anti-cancer effect. Owing to the hydrophobic characteristics of curcumin which have resulted in low bioavailability in cancer cells, the engineering curcumin into nanoparticles is therefore a viable solution to overcomes its limitation. In order to maintain a sustained release profile of curcumin nanoparticles, curcumin nanoparticles were loaded (Cur-NPs) onto hydroxyapatite (HA) via physical adsorption. To regulate the adsorption capacity of Cur-NPs onto HA, we functionalized HA with different carboxylic acids (lactic acid, tartaric acid and citric acid). The presence of carboxylic groups on HA significantly affected the binding and the release profile of Cur-NPs. The effects of Cur-NPs loaded HA were evaluated on breast cancer cell line (MCF-7), which included cell proliferation, cellular uptake of Cur-NPs, apoptosis and cell cycle analysis. The results showed that carboxylic acid-functionalized HA demonstrated higher anti-proliferating activity and time dependent cytoplasmic uptake of Cur-NPs in MCF-7 cells compared to unmodified HA. In addition, Cur-NPs loaded on functionalized HA induced higher apoptosis and cell cycle arrest in MCF-7 cells compared to unmodified HA. The present study indicates that the delivery of Cur-NPs to breast cancer using carboxylic acid-functionalized HA carrier could improve their anti-cancer activities.
INTRODUCTION: The effectiveness of conventional cancer chemotherapy is hampered by the occurrence of multidrug resistance (MDR) in tumor cells. Although many studies have reported the development of novel MDR chemotherapeutic agents, clinical success is lacking owing to the high associated toxicity. Nanoparticle-based delivery of chemotherapeutic drugs has emerged as alternative approach to treat MDR cancers via exploitation of leaky vasculature in the tumor microenvironment. Accordingly, functionalization of nanoparticles with target specific ligands can be employed to achieve significant improvements in the treatment of MDR cancer. Areas covered: This review focuses on the recent advances in the functionalization of nanocarriers with specific ligands, including antibodies, transferrin, folate, and peptides to overcome MDR cancer. The limitations of effective ligand-functionalized nanoparticles as well as therapeutic successes in ligand targeting are covered in the review. Expert opinion: Targeting MDR tumors with ligand-functionalized nanoparticles is a promising approach to improve the treatment of cancer. With this approach, higher drug concentrations at targeted sites would be achieved with lower dosage frequencies and reduced side effects in comparison to existing formulations of chemotherapeutic drugs. However, potential toxicities and immunological responses to ligands should be carefully reviewed for viable options in for future MDR cancer treatment.