Thermosensitive Drug Delivery System SBA-15-PEI for Controlled Release of Nonsteroidal Anti-Inflammatory Drug Diclofenac Sodium Salt: A Comparative Study.

Lubos Zauska,Stefan Bova,Jozef Bednarcik,Miroslav Almasi,Virginie Hornebecq,Eva Benova,Matej Balaz,Vladimir Zelenak

doi:10.3390/ma14081880

Abstract

Mesoporous SBA-15 silica material was prepared by the sol–gel method and functionalized with thermosensitive polyethylenimine polymers with different molecular weight (g·mol−1): 800 (SBA-15(C)-800), 1300 (SBA-15(C)-1300) and 2000 (SBA-15(C)-2000). The nonsteroidal anti-inflammatory drug (NSAID) diclofenac sodium was selected as a model drug and encapsulated into the pores of prepared supports. Materials were characterized by the combination of infrared spectroscopy (IR), atomic force microscopy (AFM), transmission electron microscopy (TEM), photon cross-correlation spectroscopy (PCCS), nitrogen adsorption/desorption analysis, thermogravimetry (TG), differential scanning calorimetry (DSC) and small-angle X-ray diffraction (SA-XRD) experiments. The drug release from prepared matrixes was realized in two model media differing in pH, namely small intestine environment/simulated body fluid (pH = 7.4) and simulated gastric fluid (pH = 2), and at different temperatures, namely normal body temperature (T = 37 °C) and inflammatory temperature (T = 42 °C). The process of drug loading into the pores of prepared materials from the diclofenac sodium salt solutions with different concentrations and subsequent quantitative determination of released drugs was analyzed by UV-VIS spectroscopy. Analysis of prepared SBA-15 materials modified with polyethylenimines in solution showed a high ability to store large amounts of the drug, up to 230 wt.%. Experimental results showed their high drug release into the solution at pH = 7.4 for both temperatures, which is related to the high solubility of diclofenac sodium in a slightly alkaline environment. At pH = 2, a difference in drug release rate was observed between both temperatures. Indeed, at a higher temperature, the release rates and the amount of released drug were 2–3 times higher than those observed at a lower temperature. Different kinetic models were used to fit the obtained drug release data to determine the drug release rate and its release mechanism. Moreover, the drug release properties of prepared compounds were compared to a commercially available medicament under the same experimental conditions.

Highlights

Oncological and/or infectious diseases often cause inflammation in the human body [1].Inflammation can have a local character or spread throughout the whole human body, accompanied by symptoms such as pain, fever and other complications
We prepared, characterized and described novel thermosensitive materials based on mesoporous silica SBA-15 functionalized with polyethylenimines for controlled drug release of diclofenac sodium salt
The as-synthesized SBA-15 matrix was prepared by the sol–gel method, and the surfactant located in pores was carefully removed by a combination of extraction and calcination processes

Summary

Introduction

Oncological and/or infectious diseases often cause inflammation in the human body [1]. Inflammation can have a local character or spread throughout the whole human body, accompanied by symptoms such as pain, fever and other complications. Anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics [2] are effective inflammatory suppressants. These medications are often invasive and addictive and can exhibit negative long-term side effects such as liver, kidney, heart and bone marrow damage. DDSs are biocompatible structures in which the drug is encapsulated and released only at the targeted site is reached. It is possible to make DDSs from proteins, lipids and polysaccharides [12], but the most common materials are combinations of mentioned structures [13]

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Conclusion