Abstract

Based on the formation of carbodiimide compounds between carboxyl and primary amines, hollow microspheres arising from the folic acid (folate-FA) grafted onto the surface of the modified hydroxyapatite were successfully prepared. The hollow morphology and composition of the FA-grafted hydroxyapatite microspheres were confirmed by scanning electron microscopy (SEM) and other characterizations. Brunauer-Emmett-Teller (BET) assay revealed the specific surface area and average pore size of the microspheres were 34.58m2/g and 17.80 nm, respectively. As a drug carrier, the kinetic investigation of doxorubicin (DOX) loaded shows that the adsorbed behavior of drug on the adsorbent is more suitable to be described with pseudo-first-order model. Furthermore, the release rate can reach 83% at pH 5.7, which is greater than the release of 39% at pH 7.4, indicating an excellent performance of controlled drug release for response pH. The release mechanism of DOX coincides with Fickian diffusion as a result of Korsmeyer-Peppas model analysis and the release phenomena can be well explained by Fickian diffusion second law.

Highlights

  • In recent years, hydroxyapatite has received great attention in tissue engineering and biomedical areas due to its similarity to the mineral component of bone tissues [1,2,3], excellent biocompatibility [4,5,6], and bioactivity as well as osteoconductive feature without causing local or systemic toxicity and inflammation [7, 8]

  • It is well known that folic acid is one of the receptor mediated targeting moieties [17,18,19] and its receptor shows an overexpression on the surfaces of cancer cells, such as breast, brain, kidney, and ovarian

  • A uniform spherical morphology can be clearly observed, and some broken shapes with hollow interior indicate that the as-prepared microspheres have a porous hollow structure, and the average diameters are around 2.0 μm

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Summary

Introduction

Hydroxyapatite has received great attention in tissue engineering and biomedical areas due to its similarity to the mineral component of bone tissues [1,2,3], excellent biocompatibility [4,5,6], and bioactivity as well as osteoconductive feature without causing local or systemic toxicity and inflammation [7, 8]. As for the applications of biological medicine fields, the hydroxyapatite has been extensively investigated as control-released carriers of drug, such as antibiotics [9,10,11], 5-flurouracil [12], and protein drugs [13, 14]. In order to overcome these issues and improve therapeutic efficacy, many researchers have focused on such a kind of explorations to modify hydroxyapatite particles with specific ligands as a drug control-released carriers. The hydroxyapatite can be either functionalized by polyethylene glycol (PEG) in advance or directly functionalized with folic acid [21] or aminated folic acid [22], and the relevant assessments showed that these modified microparticles could be a great candidate for biomedical application. The microparticles mentioned above do not possess the hollow morphology that has been noticed

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