Preparation and characterization of hydroxyapatite/collagen/poly-L-lactic acid three-dimensional porous reservoir type drug carrier for controlled release

Zhenlin WANG; Tao WAN; Yuhua YAN

ABSTRACT

BACKGROUND:

In the clinical therapy for orthopedic diseases, the traditional administration easily induces the great fluctuation of drug concentration and side effect, and implanted drug carrier material hydroxyapatite (Hap) cannot be used in human's load bearing parts due to its poor mechanical performances, and poly-L-lactic acid (PLLA) is effortlessly degraded to acid byproducts. Drug carriers made from Hap/PLLA are supposed to not only persist releasing drug onto the lesion and reduce the side effect,but also obtain strength enhancement and eliminate tissue inflammatory reaction in favor of bone regeneration.

OBJECTIVE:

To observe the preparation of absorbable target control-release drug carrier and simulate the application of drugs.

DESIGN:

Observation trial.

SETTING:

Chongqing Institute of Technology and Wuhan University of Technology.MATERIALS Tails of albino rats and PLLA (offered by Biological Center of Wuhan University of Technology), pepsin (110 000, Sigma company), Ca(OH)2, strong phosphoric, NaOH, glacial acetic acid, phosphate buffer (pH=7.4), 1,4-dioxane, absolute alcohol (Analytical reagent available on market).

METHODS:

The experiment was carried out in Chongqing Institute of Technology and Wuhan University of Technology. ①Type Ⅰ collagen (Col)was prepared by acid dissolution and alkali purification methods. Hap/Col bone-like biomimetic composite was synthesized through self-assembly mechanism of materials simulating in vitro biomineralization process of nature bone. X ray diffraction analysis and transmission electron microscope were applied to observe the characterization of composite's structure and morphology. ②The resultant product of HAP/Col composite was further synthesized with PLLA to prepare the three-dimensional porous reservoir type carrier for controlled release of drug employing thermal-induced phase separation technique. Scanning electron microscope, material test machine and specific gravity test method were used to investigate the pore structure and mechanical property of carrier material. ③The prepared Hap/Col/PLLA drug carrier was loaded with bromothymol blue to investigate in vitro control-release characteristic in simulated body fluid.MAIN OUTCOME

MEASURES:

①Characterization of structure and morphology of Hap/Col bone-like biomimetic composite; ②Evaluation on the property and preparation technique of Hap/Col/PLLA drug carrier; ③Assessment on results of in vitro control-release trail of model composite.

RESULTS:

①Hap nanocrystals formed as slender needles aligning with its crystalline c-axis preferentially oriented.②Hap/Col/PLLA drug carrier possessed apt pore configuration and physical properties for drug controlrelease.③In vitro release test by model compound revealed an approximate zero-orderslow release prior to its 80% release percentage.

CONCLUSION:

Hap/Col composite material is similar with natural bone, and Hap/Col/PLLA reservoir carrier can control drug release.