- Email: [email protected]
Silica nanoparticles as a carrier in the controlled release of florfenicol
J. DRUG DEL. SCI. TECH., 20 (5) 349-352 2010
Silica nanoparticles as a carrier in the controlled release of florfenicol M. Song1*, Y. Li2, A. Ning1, S. Fang3, B. Cui1* 1 Henan Agricultural University, Zhengzhou 450002, PR China Department of Education, Henan Institute of Science and Technology, Xinxiang, 453003, PR China 3 Key laboratory of surf ace and interface science, Zhengzhou University of Light Industry, Zhengzhou 450002, PR China *Correspondence: [email protected], [email protected] 2
The aim of this study was to use silica nanoparticles as the carrier to load florfenicol in aqueous solution. Florfenicol, which was selected as a model molecule because it is a broad-spectrum antibiotic drug with poor solubility in water, was adsorbed onto silica nanoparticles in aqueous solution through a natural cooling process from 95 °C to room temperature. Tween 80 was added as a stabilizer to limit the growth of drug-loaded particles. The florfenicol-loaded silica particles were characterized by transmission electron microscopy, Zetasizer laser particle size analyser, Fourier transform infrared spectrum, thermal gravimetric analysis and ultraviolet-visible light spectroscopy. The results show that florfenicol was adsorbed onto silica nanoparticles without degradation at a loading of 28.92 wt %; in contrast to the rapid release of pure florfenicol, the drug-loaded silica particles showed a slower release of florfenicol over a longer time. Key words: Silica nanoparticles – Florfenicol – Controlled release.
Drug release technology has been developed rapidly in recent years and has become one of the most important fields in modern medication. Various kinds of silica, including mesoporous silica, silica xerogel and silica areogel, have been used as carriers for sustained and controlled drug release due to their high levels of chemical and thermal stability, good biocompatibility and favourable tissue response [1-19]. The preparation of a silica carrier usually involves preparation of a silica sol and a subsequent gelation process, such as supercritical drying, spray-drying or emulsion chemistry [1, 11, 19]. Drug molecules can be encapsulated easily with silica carriers by combining sol–gel polymerisation [1]. However, these gelation processes are usually time-consuming and expensive, which might not be propitious to their application into some fields, such as veterinary drugs. In addition, the hydrophilic surface of the silica carrier needs to be modified to improve its affinity to drugs which are poorly soluble in water [20], and organic solvents are usually used to achieve the desired drug concentration [7, 15, 16, 19]. Both of these processes increase the complexity and the cost of production. In the present work, we focused on an attempt to use silica nanoparticles to load florfenicol in aqueous solution. The silica nanoparticles are conventionally made with an inexpensive sodium silicate solution called water glass as the starting material. This method has two advantages: it is inexpensive and the huge specific surface of silica nanoparticles is not wasted due to aggregation because they are well dispersed in aqueous solution. Florfenicol was chosen as the drug model because it is a broad spectrum antibiotic for application in bacterial infections due to susceptible pathogens in birds, reptiles, fish, shellfish and mammals. Although the drug is poorly soluble in water (approximately 1 mg/mL), there are hydrophilic groups such as –OH, –NH and –C=O in its molecular structure (Figure 1), which might make it possible to be loaded by silica nanoparticles in aqueous solution, and thus reduce the cost by avoiding the use of organic solvents.
Cl
O
HO
O S
Cl
HN
O
F Figure 1 - Molecular structure of florfenicol.
Biyun Days Animal Pharmaceutical Co. Sodium dihydrogen phosphate (NaH2PO3), sodium hydrogen phosphate (Na2HPO3) and Tween 80 were all of analytical grade and were used as received.
2. Drug adsorption
In a typical drug-loading process, 0.3 g of florfenicol and 10 mL of silica sol were mixed and stirred with a magnetic follower in a 100-mL flask equipped with a condenser. The temperature was increased slowly and the initial turbid suspension became a semi-transparent solution at around 95 °C, indicating that all of the drug was dissolved. One drop of Tween 80 was added and the loading process was allowed to continue for half an hour and then to cool slowly to room temperature. Finally, the silica particles loaded with florfenicol were collected by centrifugation, washed with water, air-dried at 40 °C for 24 h, and finally ground to a white powder in a ceramic pestle and mortar.
3. Characterization
The amount of drug adsorbed to the carrier was determined with an American Diamond thermal gravimetric analyser (TGA). Silica nanoparticles were collected by centrifugation and air-dried for comparison. The samples were heated at a rate of 10 °C/min in a stream of nitrogen gas. The morphology of the samples was observed by transmission electron microscopy (TEM) with a JEM 100CX-a instrument. The Fourier transform infrared (FTIR) spectrum was obtained with a Cary Eclipse FTIR spectrophotometer. X-ray diffraction (XRD) patterns
I. Materials and Methods 1. Materials
Silica sol, a tasteless and non-toxic material consisting of silica nanoparticles (10-20 nm) dispersed in water, was supplied by Zhengzhou Jingwei Composite Material Co. Florfenicol was supplied by Henan
349
J. DRUG DEL. SCI. TECH., 20 (5) 349-352 2010
Silica nanoparticles as a carrier in the controlled release of florfenicol M. Song, Y. Li, A. Ning, S. Fang, B. Cui
of the samples were obtained with a D8 Advance powder diffraction meter with monochromated Cu Kα1 radiation.
4. Drug release
In vitro drug release experiments were done by placing 0.1 g of the dry powder of florfenicol-loaded silica particles into 50 mL of phosphate-buffered saline (PBS, Gibco, pH 7.4) at 37 °C. For comparison, the dissolution of florfenicol alone was investigated under the same conditions. At each time-point, a 1-mL sample was withdrawn and diluted to 5 mL with PBS. The concentration of florfenicol released was determined as a function of time from measurement of the absorbance at 266 nm (Cary 300 spectrophotometer), the characteristic adsorption wavelength of florfenicol [21]. Florfenicol standards were prepared by dissolving a weighed amount of the drug in PBS.
Figure 2 - TEM images of silica nanoparticles (a) and florfenicol-loaded silica particles (b). Inset: one magnified picture of florfenicol-loaded silica particles.
II. Results 1. TEM study
Figure 2 shows TEM images of silica nanoparticles (a) and florfenicol-loaded silica particles (b). As Figure 2a shows, silica nanoparticles are spherical with a diameter of 15-20 nm and no aggregation was detected. The florfenicol-loaded silica particles are larger (Figure 2b) and they consist of tens of silica nanoparticles that aggregate (inset in Figure 2b), and their average size is about 179 nm as determined with a Zetasizer laser particle size analyser (Figure 3). The results indicate that florfenicol-loaded silica particles tend to aggregate after the adsorption of florfenicol molecules, but the presence of the surfactant tween 80 might lessen the aggregation to some extent.
Figure 3 - Size distribution of florfenicol-loaded silica particles.
2. Drug adsorption
The FTIR spectrum of florfenicol-loaded silica particles was recorded and compared with those of pure florfenicol and the carrier silica nanoparticles alone (Figure 4). For silica nanoparticles, the bands at 3,440, at 1,108 and 470 and at 807 cm-1 are ascribed to the absorbance by hydrogen-bonded Si-OH groups, siloxane groups (–Si–O–Si–) and silanol groups (Si-OH), respectively [22, 23]. In the case of florfenicol-loaded silica particles, almost all of the characteristic peaks were found to be identical with that of the pure drug, except the broad absorption peak between 1,400 and 1,000 cm-1, which might be the combined absorption of silica and florfenicol. This result indicates that the drug might be physically adsorbed onto the carrier. The loading weight percentage (W) of florfenicol on silica particles was determined with a TGA (Figure 5). The TGA profile of florfenicol shows two stages of weight loss. It is clear that the drug molecule decomposes at temperature above 200 °C and is destroyed at temperature above 750 °C. For blank silica nanoparticles, the TGA profile shows no detectable weight loss at temperatures above 200 °C. The TGA profile of florfenicol-loaded silica particles is similar to that of the pure drug but the weight loss is less. The weight loss of surfactant remaining on the particle can be neglected because the amount is negligible after washing with water. Therefore, the weight loss of florfenicol-loaded silica particles from 200-750 °C is about 28.92 wt % and can be determined approximately as the loading weight percentage (W) of florfenicol on silica particles. In addition, it is believed that no degradation occurred during the drug-loading procedure based on the following points. First, the FTIR spectrum and the TG curve are similar to those of pure florfenicol. Secondly, the drug molecule decomposes at a higher temperature than the treatment temperature of 95 °C as the TG curve shows. Finally, the X-ray diffraction pattern of the drug after treatment at 95 ºC is identical with that of the original drug (Figure 6).
Figure 4 - FTIR spectra of silica nanoparticles, florfenicol and florfenicolloaded silica particles.
3. Drug release
Figure 7 shows the cumulative release of florfenicol as a function of time. For comparison, the dissolution of the free drug was
Figure 5 - TGA profiles of silica nanoparticles, florfenicol and florfenicolloaded silica particles. 350
Silica nanoparticles as a carrier in the controlled release of florfenicol M. Song, Y. Li, A. Ning, S. Fang, B. Cui
J. DRUG DEL. SCI. TECH., 20 (5) 349-352 2010
Figure 8 - The formation schematic map of florfenicol-loaded silica particles.
Correspondingly, the florfenicol release curve from the silica nanoparticles can be divided roughly into two stages. The first stage was a burst release of nearly 80 % within the initial 35 h, which was due to the dissolution of the drug adsorbed onto the surface of the drug-loaded silica particles. The second stage was a slower release of florfenicol, from 80 to 97 % within the following 135 h, which might arise from the release of florfenicol adsorbed directly onto the surface of the silica nanoparticles. The delayed release might be ascribed to the fact that the release fluid must wet the carrier so that the drug molecules are desorbed from the carrier before diffusion into the solution.
Figure 6 - XRD patterns of pure florfenicol and the drug after treatment at 95 °C.
* The drug florfenicol was incorporated successfully into silica nanoparticles in aqueous solution. The release of the drug from the silica particles was time-dependent. In comparison to the release of pure florfenicol, the release from the drug-loaded silica particles was slower and occurred over a longer time. Therefore, the work presented here provides the basic data for the use of silica nanoparticles to carry a drug with poor solubility in water for controlled release.
Figure 7 - Commulative release of florfenicol as a function of time.
also investigated. There is a major difference in the two curves. For florfenicol alone, the curve shows a rapid dissolution within the first 6 h, reaching 74.9 %, and reaching 100 % after 48 h. In contrast to the brief, short-term release of pure florfenicol, the drug incorporated onto the silica nanoparticles shows a slower and longer-term release and the percentage of florfenicol released was only 50 and 83 % within 6 and after 48 h, respectively. It takes nearly 170 h to reach 97 % of florfenicol release from the silica particles. It is clear from these results that the adsorption onto the silica nanoparticles markedly delays the release of the florfenicol into solution.
References 1. 2.
3.
III. Discussion
As expected, florfenicol-loaded silica particles were successfully synthesized using silica nanoparticles as carrier in aqueous solution. In this study, the solubility of florfenicol in water was increased from 1 mg/mL at room temperature to 30 mg/mL at around 95 °C. When the supersaturated solution was cooled slowly to room temperature, large needle-like crystals appeared. In contrast, with silica nanoparticles and surfactant added, only powder was obtained even when more drug was added to the solution. The model of the generation of drug-loaded particles is shown schematically in Figure 8. First, when the drug was added to the aqueous solution of silica nanoparticles, the drug molecules were adsorbed onto the silica nanoparticles through the interaction of hydrophilic groups of the drug with silanol groups of the silica particles. Secondly, silica nanoparticles aggregated in aqueous solution and they acted as seeds to attract more drug molecules when the solution was cooled. However, the surfactant molecules surrounded the particles and limited the aggregation and the growth to some extent. As a result, larger particles consisting of tens of florfenicol-loaded silica nanoparticles were formed.
4. 5. 6. 7.
8.
9.
351
Barbe C., Bartlett J., Kong L., Finnie K., Lin H.Q., Larkin M. Silica particles: a novel drug delivery system. - Adv. Mater., 16, 1959-1966, 2004. Kortesuo P., Ahola M., Karlsson S., Kangasniemi I., Yli-Urpo A., Kiesvaara J. - Silica xerogel as an implantable carrier for controlled drug delivery evaluation of drug distribution and tissue effects after implantation. - Biomaterials, 21, 193-198, 2000. Ahola M., Kortesuo P., Kangasniemi I., Kiesvaara J., Yli-Urpo A. - Silica xerogel carrier material for controlled release of toremifene citrate. - Int. J. Pharm., 195, 219-227, 2000. Chen J.F., Ding H.M., Wang J.X., Shao L. - Preparation and characterization of porous hollow silica nanoparticles for drug delivery application. - Biomaterials, 25, 723-727, 2004. Li Z.Z., Wen L.X., Shao L., Chen J.F. - Fabrication of porous hollow silica nanoparticles and their applications in drug release control. - J. Control. Release, 98, 245-254, 2004. Xu W., Gao Q., Xu Y., Wu D., Sun Y. - pH-Controlled drug release from mesoporous silica tablets coated with hydroxypropyl methylcellulose phthalate. - Mater. Res. Bul., 44, 606-612, 2009. Lin C.X., Qiao S.Z., Yu C.Z., Ismadji S., Lu G.Q. - Periodic mesoporous silica and organosilica with controlled morphologies as carriers for drug release. - Microporous Mesoporous Mater., 117, 213-219, 2009. Mavera U., Godeca A., Bele M., Planinsek O., Gaberscek M., Srcic S., Jamnik J. - Novel hybrid silica xerogels for stabilization and controlled release of drug. - Int. J. Pharm., 330, 164-174, 2007. Slowing I.I., Escoto J.L.V., Wu C.-W., Lin V.S.-Y. - Mesoporous silica nanoparticles as controlled release drug delivery and gene
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Silica nanoparticles as a carrier in the controlled release of florfenicol M. Song, Y. Li, A. Ning, S. Fang, B. Cui
transfection carriers. - Adv. Drug Deliv. Rev., 60, 1278-1288, 2008. Guenther U., Smirnova I., Neubert R.H.H. - Hydrophilic silica aerogels as dermal drug delivery systems, Dithranol as a model drug. - Eur. J. Pharm. Biopharm., 69, 935-942, 2008. Smirnova I., Suttiruengwong S., Arlt W. - Feasibility study of hydrophilic and hydrophobic silica aerogels as drug delivery systems. - J. Non-Crystal. Sol., 350, 54-60, 2004. Prokopowicz M. - Correlation between physicochemical properties of doxorubicin-loaded silica/polydimethylsiloxane xerogel and in vitro release of drug. - Acta Biomaterialia, 5, 193-207, 2009. Xu W., Gao Q., Xu Y., Wu D., Sun Y., Shen W., Deng F. - Controlled drug release from bifunctionalized mesoporous silica. - J. Solid. State Chem., 181, 2837-2844, 2008. Kortesuo P., Ahola M., Kangas M., Leino T., Laakso S., Vuorilehto L., Yli-Urpo A., Kiesvaara J., Marvola M. - Alkyl-substituted silica gel as a carrier in the controlled release of dexmedetomidine. - J. Control. Release, 76, 227-238, 2001. Tang Q., Xu Y., Wu D., Sun Y. - A study of carboxylic-modified mesoporous silica in controlled delivery for drug famotidine. - J. Solid. State. Chem., 179, 1513-1520, 2006. Charnay C., Begu S., Tourne-Peteilh C., Nicole L., Lerner D.A., Devoisselle J.M. - Inclusion of ibuprofen in mesoporous templated drug loading and release property. - Eur. J. Pharm. Biopharm., 57, 533-540, 2004. Kortesuo P., Ahola M., Kangas M., Yli-Urpo A., Kiesvaara J., Marvola M.I. - In vitro release of dexmedetomidine from silica xerogel monoliths: effect of sol-gel synthesis parameters. - Int. J. Pharm., 221, 107-114, 2001. Radin S., Bassyouni G., Vresilovic E.J., Schepers E., Ducheyne P. - In vivo tissue response to resorbable silica xerogels as
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Acknowledgements This work was supported by the National Natural Science Foundation of China (grant number 50701016), key project in the national science & technology (2006BAD06A08)) of China, the doctor foundation (30700351) and the personnel postdoctoral management fees (10400012) from Henan Agricultural University.
Manuscript Received 8 March 2010, accepted for publication 14 June 2010.
352
Silica nanoparticles as a carrier in the controlled release of florfenicol M. Song1*, Y. Li2, A. Ning1, S. Fang3, B. Cui1* 1 Henan Agricultural University, Zhengzhou 450002, PR China Department of Education, Henan Institute of Science and Technology, Xinxiang, 453003, PR China 3 Key laboratory of surf ace and interface science, Zhengzhou University of Light Industry, Zhengzhou 450002, PR China *Correspondence: [email protected], [email protected] 2
The aim of this study was to use silica nanoparticles as the carrier to load florfenicol in aqueous solution. Florfenicol, which was selected as a model molecule because it is a broad-spectrum antibiotic drug with poor solubility in water, was adsorbed onto silica nanoparticles in aqueous solution through a natural cooling process from 95 °C to room temperature. Tween 80 was added as a stabilizer to limit the growth of drug-loaded particles. The florfenicol-loaded silica particles were characterized by transmission electron microscopy, Zetasizer laser particle size analyser, Fourier transform infrared spectrum, thermal gravimetric analysis and ultraviolet-visible light spectroscopy. The results show that florfenicol was adsorbed onto silica nanoparticles without degradation at a loading of 28.92 wt %; in contrast to the rapid release of pure florfenicol, the drug-loaded silica particles showed a slower release of florfenicol over a longer time. Key words: Silica nanoparticles – Florfenicol – Controlled release.
Drug release technology has been developed rapidly in recent years and has become one of the most important fields in modern medication. Various kinds of silica, including mesoporous silica, silica xerogel and silica areogel, have been used as carriers for sustained and controlled drug release due to their high levels of chemical and thermal stability, good biocompatibility and favourable tissue response [1-19]. The preparation of a silica carrier usually involves preparation of a silica sol and a subsequent gelation process, such as supercritical drying, spray-drying or emulsion chemistry [1, 11, 19]. Drug molecules can be encapsulated easily with silica carriers by combining sol–gel polymerisation [1]. However, these gelation processes are usually time-consuming and expensive, which might not be propitious to their application into some fields, such as veterinary drugs. In addition, the hydrophilic surface of the silica carrier needs to be modified to improve its affinity to drugs which are poorly soluble in water [20], and organic solvents are usually used to achieve the desired drug concentration [7, 15, 16, 19]. Both of these processes increase the complexity and the cost of production. In the present work, we focused on an attempt to use silica nanoparticles to load florfenicol in aqueous solution. The silica nanoparticles are conventionally made with an inexpensive sodium silicate solution called water glass as the starting material. This method has two advantages: it is inexpensive and the huge specific surface of silica nanoparticles is not wasted due to aggregation because they are well dispersed in aqueous solution. Florfenicol was chosen as the drug model because it is a broad spectrum antibiotic for application in bacterial infections due to susceptible pathogens in birds, reptiles, fish, shellfish and mammals. Although the drug is poorly soluble in water (approximately 1 mg/mL), there are hydrophilic groups such as –OH, –NH and –C=O in its molecular structure (Figure 1), which might make it possible to be loaded by silica nanoparticles in aqueous solution, and thus reduce the cost by avoiding the use of organic solvents.
Cl
O
HO
O S
Cl
HN
O
F Figure 1 - Molecular structure of florfenicol.
Biyun Days Animal Pharmaceutical Co. Sodium dihydrogen phosphate (NaH2PO3), sodium hydrogen phosphate (Na2HPO3) and Tween 80 were all of analytical grade and were used as received.
2. Drug adsorption
In a typical drug-loading process, 0.3 g of florfenicol and 10 mL of silica sol were mixed and stirred with a magnetic follower in a 100-mL flask equipped with a condenser. The temperature was increased slowly and the initial turbid suspension became a semi-transparent solution at around 95 °C, indicating that all of the drug was dissolved. One drop of Tween 80 was added and the loading process was allowed to continue for half an hour and then to cool slowly to room temperature. Finally, the silica particles loaded with florfenicol were collected by centrifugation, washed with water, air-dried at 40 °C for 24 h, and finally ground to a white powder in a ceramic pestle and mortar.
3. Characterization
The amount of drug adsorbed to the carrier was determined with an American Diamond thermal gravimetric analyser (TGA). Silica nanoparticles were collected by centrifugation and air-dried for comparison. The samples were heated at a rate of 10 °C/min in a stream of nitrogen gas. The morphology of the samples was observed by transmission electron microscopy (TEM) with a JEM 100CX-a instrument. The Fourier transform infrared (FTIR) spectrum was obtained with a Cary Eclipse FTIR spectrophotometer. X-ray diffraction (XRD) patterns
I. Materials and Methods 1. Materials
Silica sol, a tasteless and non-toxic material consisting of silica nanoparticles (10-20 nm) dispersed in water, was supplied by Zhengzhou Jingwei Composite Material Co. Florfenicol was supplied by Henan
349
J. DRUG DEL. SCI. TECH., 20 (5) 349-352 2010
Silica nanoparticles as a carrier in the controlled release of florfenicol M. Song, Y. Li, A. Ning, S. Fang, B. Cui
of the samples were obtained with a D8 Advance powder diffraction meter with monochromated Cu Kα1 radiation.
4. Drug release
In vitro drug release experiments were done by placing 0.1 g of the dry powder of florfenicol-loaded silica particles into 50 mL of phosphate-buffered saline (PBS, Gibco, pH 7.4) at 37 °C. For comparison, the dissolution of florfenicol alone was investigated under the same conditions. At each time-point, a 1-mL sample was withdrawn and diluted to 5 mL with PBS. The concentration of florfenicol released was determined as a function of time from measurement of the absorbance at 266 nm (Cary 300 spectrophotometer), the characteristic adsorption wavelength of florfenicol [21]. Florfenicol standards were prepared by dissolving a weighed amount of the drug in PBS.
Figure 2 - TEM images of silica nanoparticles (a) and florfenicol-loaded silica particles (b). Inset: one magnified picture of florfenicol-loaded silica particles.
II. Results 1. TEM study
Figure 2 shows TEM images of silica nanoparticles (a) and florfenicol-loaded silica particles (b). As Figure 2a shows, silica nanoparticles are spherical with a diameter of 15-20 nm and no aggregation was detected. The florfenicol-loaded silica particles are larger (Figure 2b) and they consist of tens of silica nanoparticles that aggregate (inset in Figure 2b), and their average size is about 179 nm as determined with a Zetasizer laser particle size analyser (Figure 3). The results indicate that florfenicol-loaded silica particles tend to aggregate after the adsorption of florfenicol molecules, but the presence of the surfactant tween 80 might lessen the aggregation to some extent.
Figure 3 - Size distribution of florfenicol-loaded silica particles.
2. Drug adsorption
The FTIR spectrum of florfenicol-loaded silica particles was recorded and compared with those of pure florfenicol and the carrier silica nanoparticles alone (Figure 4). For silica nanoparticles, the bands at 3,440, at 1,108 and 470 and at 807 cm-1 are ascribed to the absorbance by hydrogen-bonded Si-OH groups, siloxane groups (–Si–O–Si–) and silanol groups (Si-OH), respectively [22, 23]. In the case of florfenicol-loaded silica particles, almost all of the characteristic peaks were found to be identical with that of the pure drug, except the broad absorption peak between 1,400 and 1,000 cm-1, which might be the combined absorption of silica and florfenicol. This result indicates that the drug might be physically adsorbed onto the carrier. The loading weight percentage (W) of florfenicol on silica particles was determined with a TGA (Figure 5). The TGA profile of florfenicol shows two stages of weight loss. It is clear that the drug molecule decomposes at temperature above 200 °C and is destroyed at temperature above 750 °C. For blank silica nanoparticles, the TGA profile shows no detectable weight loss at temperatures above 200 °C. The TGA profile of florfenicol-loaded silica particles is similar to that of the pure drug but the weight loss is less. The weight loss of surfactant remaining on the particle can be neglected because the amount is negligible after washing with water. Therefore, the weight loss of florfenicol-loaded silica particles from 200-750 °C is about 28.92 wt % and can be determined approximately as the loading weight percentage (W) of florfenicol on silica particles. In addition, it is believed that no degradation occurred during the drug-loading procedure based on the following points. First, the FTIR spectrum and the TG curve are similar to those of pure florfenicol. Secondly, the drug molecule decomposes at a higher temperature than the treatment temperature of 95 °C as the TG curve shows. Finally, the X-ray diffraction pattern of the drug after treatment at 95 ºC is identical with that of the original drug (Figure 6).
Figure 4 - FTIR spectra of silica nanoparticles, florfenicol and florfenicolloaded silica particles.
3. Drug release
Figure 7 shows the cumulative release of florfenicol as a function of time. For comparison, the dissolution of the free drug was
Figure 5 - TGA profiles of silica nanoparticles, florfenicol and florfenicolloaded silica particles. 350
Silica nanoparticles as a carrier in the controlled release of florfenicol M. Song, Y. Li, A. Ning, S. Fang, B. Cui
J. DRUG DEL. SCI. TECH., 20 (5) 349-352 2010
Figure 8 - The formation schematic map of florfenicol-loaded silica particles.
Correspondingly, the florfenicol release curve from the silica nanoparticles can be divided roughly into two stages. The first stage was a burst release of nearly 80 % within the initial 35 h, which was due to the dissolution of the drug adsorbed onto the surface of the drug-loaded silica particles. The second stage was a slower release of florfenicol, from 80 to 97 % within the following 135 h, which might arise from the release of florfenicol adsorbed directly onto the surface of the silica nanoparticles. The delayed release might be ascribed to the fact that the release fluid must wet the carrier so that the drug molecules are desorbed from the carrier before diffusion into the solution.
Figure 6 - XRD patterns of pure florfenicol and the drug after treatment at 95 °C.
* The drug florfenicol was incorporated successfully into silica nanoparticles in aqueous solution. The release of the drug from the silica particles was time-dependent. In comparison to the release of pure florfenicol, the release from the drug-loaded silica particles was slower and occurred over a longer time. Therefore, the work presented here provides the basic data for the use of silica nanoparticles to carry a drug with poor solubility in water for controlled release.
Figure 7 - Commulative release of florfenicol as a function of time.
also investigated. There is a major difference in the two curves. For florfenicol alone, the curve shows a rapid dissolution within the first 6 h, reaching 74.9 %, and reaching 100 % after 48 h. In contrast to the brief, short-term release of pure florfenicol, the drug incorporated onto the silica nanoparticles shows a slower and longer-term release and the percentage of florfenicol released was only 50 and 83 % within 6 and after 48 h, respectively. It takes nearly 170 h to reach 97 % of florfenicol release from the silica particles. It is clear from these results that the adsorption onto the silica nanoparticles markedly delays the release of the florfenicol into solution.
References 1. 2.
3.
III. Discussion
As expected, florfenicol-loaded silica particles were successfully synthesized using silica nanoparticles as carrier in aqueous solution. In this study, the solubility of florfenicol in water was increased from 1 mg/mL at room temperature to 30 mg/mL at around 95 °C. When the supersaturated solution was cooled slowly to room temperature, large needle-like crystals appeared. In contrast, with silica nanoparticles and surfactant added, only powder was obtained even when more drug was added to the solution. The model of the generation of drug-loaded particles is shown schematically in Figure 8. First, when the drug was added to the aqueous solution of silica nanoparticles, the drug molecules were adsorbed onto the silica nanoparticles through the interaction of hydrophilic groups of the drug with silanol groups of the silica particles. Secondly, silica nanoparticles aggregated in aqueous solution and they acted as seeds to attract more drug molecules when the solution was cooled. However, the surfactant molecules surrounded the particles and limited the aggregation and the growth to some extent. As a result, larger particles consisting of tens of florfenicol-loaded silica nanoparticles were formed.
4. 5. 6. 7.
8.
9.
351
Barbe C., Bartlett J., Kong L., Finnie K., Lin H.Q., Larkin M. Silica particles: a novel drug delivery system. - Adv. Mater., 16, 1959-1966, 2004. Kortesuo P., Ahola M., Karlsson S., Kangasniemi I., Yli-Urpo A., Kiesvaara J. - Silica xerogel as an implantable carrier for controlled drug delivery evaluation of drug distribution and tissue effects after implantation. - Biomaterials, 21, 193-198, 2000. Ahola M., Kortesuo P., Kangasniemi I., Kiesvaara J., Yli-Urpo A. - Silica xerogel carrier material for controlled release of toremifene citrate. - Int. J. Pharm., 195, 219-227, 2000. Chen J.F., Ding H.M., Wang J.X., Shao L. - Preparation and characterization of porous hollow silica nanoparticles for drug delivery application. - Biomaterials, 25, 723-727, 2004. Li Z.Z., Wen L.X., Shao L., Chen J.F. - Fabrication of porous hollow silica nanoparticles and their applications in drug release control. - J. Control. Release, 98, 245-254, 2004. Xu W., Gao Q., Xu Y., Wu D., Sun Y. - pH-Controlled drug release from mesoporous silica tablets coated with hydroxypropyl methylcellulose phthalate. - Mater. Res. Bul., 44, 606-612, 2009. Lin C.X., Qiao S.Z., Yu C.Z., Ismadji S., Lu G.Q. - Periodic mesoporous silica and organosilica with controlled morphologies as carriers for drug release. - Microporous Mesoporous Mater., 117, 213-219, 2009. Mavera U., Godeca A., Bele M., Planinsek O., Gaberscek M., Srcic S., Jamnik J. - Novel hybrid silica xerogels for stabilization and controlled release of drug. - Int. J. Pharm., 330, 164-174, 2007. Slowing I.I., Escoto J.L.V., Wu C.-W., Lin V.S.-Y. - Mesoporous silica nanoparticles as controlled release drug delivery and gene
J. DRUG DEL. SCI. TECH., 20 (5) 349-352 2010
10. 11. 12.
13. 14.
15. 16.
17.
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Silica nanoparticles as a carrier in the controlled release of florfenicol M. Song, Y. Li, A. Ning, S. Fang, B. Cui
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Acknowledgements This work was supported by the National Natural Science Foundation of China (grant number 50701016), key project in the national science & technology (2006BAD06A08)) of China, the doctor foundation (30700351) and the personnel postdoctoral management fees (10400012) from Henan Agricultural University.
Manuscript Received 8 March 2010, accepted for publication 14 June 2010.
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