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.

Highlights

  • Hydroxyapatite (HAp) (Ca10 (PO4 )6 (OH)2 ) is probably the most important type of calcium phosphate ceramic due to its increasing application in biomedicine

  • The results indicate that STR could be effectively released from both ACP and crystalline hydroxyapatite (cHAp) nanoparticles, in all cases, the release rate was slower for the cHAp than for the ACP

  • The results demonstrate that the contact angle of the fibers containing the nanoparticles loaded with the hydrophobic STR

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Summary

Introduction

Hydroxyapatite (HAp) (Ca10 (PO4 ) (OH)2 ) is probably the most important type of calcium phosphate ceramic due to its increasing application in biomedicine. The porosity of HAp offers a significant opportunity for the encapsulation of pharmacological substances, such as antibody fragments, antibiotics, hormones and enzymes This potential makes HAp a suitable biomaterial to deliver pharmacological substances with sustained release capacity in the treatment of bone problems and cancers in which local delivery helps to fill defects in the skeleton. Due to these excellent roles of HAp in biomedical applications [7], several methods have been considered for the preparation or synthesis of HAp nanoparticles with optimized and close properties to living hard tissues, such as bones and teeth. These methods include, among other techniques, chemical precipitation [8,9,10], sol-gel [8], hydrothermal [11], multiple emulsion [12], biomimetic deposition [13,14] and electrodeposition [15]

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