Tuning drug loading and release properties of diatom silica microparticles by surface modifications

• Published in: International journal of pharmaceutics 2013-02, Vol.443 (1-2), p.230-241
• Main Authors: Bariana, Manpreet, Aw, Moom Sinn, Kurkuri, Mahaveer, Losic, Dusan
• Format: Article
• Language: English
• Subjects: Bacillariophyta; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diatomaceous earth; Diatomaceous Earth - chemistry; Diatomite; Drug Carriers - chemistry; Drug delivery; epoxides; ethylene glycol; Fourier transform infrared spectroscopy; Gentamicin; Gentamicins - administration & dosage; Gentamicins - chemistry; hydrocarbons; hydrolysis; hydrophilicity; Hydrophobic and Hydrophilic Interactions; hydrophobicity; Indomethacin; Indomethacin - administration & dosage; Indomethacin - chemistry; Microscopy, Electron, Scanning; Molecular Structure; Particle Size; phosphorous acid; Photoelectron Spectroscopy; Porous materials; Silanes - chemistry; silica; Solubility; Spectroscopy, Fourier Transform Infrared; Surface modifications; Surface Properties; Thermogravimetry; Time Factors; X-ray photoelectron spectroscopy
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2012.12.012

Diatomaceous earth (DE), or diatomite silica microparticles originated from fossilized diatoms are a potential substitute for its silica-based synthetic counterparts to address limitations in conventional drug delivery. This study presents the impact of engineered surface chemistry of DE microparticles on their drug loading and release properties. Surface modifications with four silanes, including 3-aminopropyltriethoxy silane (APTES), methoxy-poly-(ethylene-glycol)-silane (mPEG-silane), 7-octadecyltrichlorosilane (OTS), 3-(glycidyloxypropyl)trimethoxysilane (GPTMS) and two phosphonic acids, namely 2-carboxyethyl-phosphonic acid (2 CEPA) and 16-phosphono-hexadecanoic acid (16 PHA) were explored in order to tune drug loading and release characteristics of water insoluble (indomethacin) and water soluble drugs (gentamicin). Successful grafting of these functional groups with different interfacial properties was confirmed using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Thermogravimetric analysis (TGA) was applied to determine the amount of loaded drugs and UV-spectrophotometry to analyse in vitro drug release from modified DE microparticles. Differences in drug release time (13–26 days) and loading capacity (14–24%) were observed depending on functional groups on the surface of DE microparticles. It was found that hydrophilic surfaces, due to the presence of polar carboxyl, amine or hydrolyzed epoxy group, favor extended release of indomethacin, while the hydrophobic DE surface modified by organic hydrocarbons gives a better sustained release profile for gentamicin. This work demonstrates that by changing surface functionalities on DE microparticles, it is possible to tune their drug loading and release characteristics for both hydrophobic and hydrophilic drugs and therefore achieve optimal drug delivery performance.