Medicated Scaffolds Prepared with Hydroxyapatite/Streptomycin Nanoparticles Encapsulated into Polylactide Microfibers

Abstract

The preparation, characterization, and controlled release of hydroxyapatite (HAp) nanoparticles loaded with streptomycin (STR) was studied. These nanoparticles are highly appropriate for the treatment of bacterial infections and are also promising for the treatment of cancer cells. The analyses involved scanning electron microscopy, dynamic light scattering (DLS) and Z-potential measurements, as well as infrared spectroscopy and X-ray diffraction. Both amorphous (ACP) and crystalline (cHAp) hydroxyapatite nanoparticles were considered since they differ in their release behavior (faster and slower for amorphous and crystalline particles, respectively). The encapsulated nanoparticles were finally incorporated into biodegradable and biocompatible polylactide (PLA) scaffolds. The STR load was carried out following different pathways during the synthesis/precipitation of the nanoparticles (i.e., nucleation steps) and also by simple adsorption once the nanoparticles were formed. The loaded nanoparticles were biocompatible according to the study of the cytotoxicity of extracts using different cell lines. FTIR microspectroscopy was also employed to evaluate the cytotoxic effect on cancer cell lines of nanoparticles internalized by endocytosis. The results were promising when amorphous nanoparticles were employed. The nanoparticles loaded with STR increased their size and changed their superficial negative charge to positive. The nanoparticles’ crystallinity decreased, with the consequence that their crystal sizes reduced, when STR was incorporated into their structure. STR maintained its antibacterial activity, although it was reduced during the adsorption into the nanoparticles formed. The STR release was faster from the amorphous ACP nanoparticles and slower from the crystalline cHAp nanoparticles. However, in both cases, the STR release was slower when incorporated in calcium and phosphate during the synthesis. The biocompatibility of these nanoparticles was assayed by two approximations. When extracts from the nanoparticles were evaluated in cultures of cell lines, no cytotoxic damage was observed at concentrations of less than 10 mg/mL. This demonstrated their biocompatibility. Another experiment using FTIR microspectroscopy evaluated the cytotoxic effect of nanoparticles internalized by endocytosis in cancer cells. The results demonstrated slight damage to the biomacromolecules when the cells were treated with ACP nanoparticles. Both ACP and cHAp nanoparticles were efficiently encapsulated in PLA electrospun matrices, providing functionality and bioactive properties.

Perspective Chapter: Hydroxyapatite – Surface Functionalization to Prevent Bacterial Colonization

“…Another approach is to use electrochemical methods, such as electrodeposition [34, 87-89], micro-arc oxidation [90], and electrophoretic deposition [91], to generate HA coatings containing antimicrobial compounds. Electrospinning can be used for the creation of composite nanofibers and coatings with a combination of functionalized-HA nanoparticles and antimicrobial compounds [92][93][94]. Other methodologies include the spraying of a solution containing the precursors of HA mixed with the antibacterial compound [95][96][97].…”

“…Covalent immobilization of antibiotics like doxorubicin can be achieved using HA nanoparticles functionalized with amino groups or by more complicated methods, including the fabrication of polymer brushes, to anchor aminoglycoside antibiotics, such as gentamycin, to HA substrates [110,111]. Furthermore, aminoglycosides antibiotics, such as streptomycin, have been encapsulated in HA nanoparticles [93].…”

Multifunctional Scaffolds Based on Emulsion and Coaxial Electrospinning Incorporation of Hydroxyapatite for Bone Tissue Regeneration

“…In addition to being a wide-spectrum antibiotic, it can be used in cancer therapy due to the proven capacity of CAM to induce the mitochondrial dysfunction of cancer cells [ 42 , 43 ]. HAp NPs loaded with streptomycin antibiotics have recently been revealed to be appropriate against bacterial infections and appear also promising for the treatment of cancer cells [ 44 ].…”

Hydroxyapatite Biobased Materials for Treatment and Diagnosis of Cancer

“…When the STR-HAp NPs were incorporated into PLA fibers, a slower and prolonged drug release was obtained, reaching a 50% at the first 20 h of analysis. In both DDS-PLA scaffold cases, no higher cytotoxicity values were attributable to a slower drug release from the PLA matrices [ 118 ]. Other experiments with PLA-HAp were carried out by Lee et al They encapsulated paclitaxel into PLA-HAp NPs and tested in vitro the NPs against murine breast cancer cells, reporting an 80% reduction in cell viability at 48 h [ 119 ].…”