- Email: [email protected]
Preparation and pharmacokinetics of solid lipid nanoparticles loaded with pueraria flavones
Abstracts / Journal of Controlled Release 152 (2011) e1–e132
scanning electron microscopy measurements. Intramicellar crosslinking enhanced the micelle stability against dilution in aqueous solution, and at the same time, controllable micellar permeability was obtained. Water insoluble model drug ADR was successfully trapped in the hydrophobic core domain of the micelles and showed a sustained and remarkably slower release behavior. The crosslinked micelles prepared from crosslinkable and amphiphilic phospholipid random copolymers with a cell outer membrane mimetic shell could be a promising candidate for prolonged circulating drug delivery carriers, especially for intravenous administration. Acknowledgments This work was supported by the National Natural Science Foundation of China (20774073, 20974087), and NWU Graduate Innovation and Creativity Funds (07YZZ22, 09YZZ46). References [1] G.S. Kwon, K. Kataoka, Polymeric micelles as mew drug carriersAdv. Drug Deliv. Rev. 21 (1996) 107–116. [2] C. Allen, D. Maysinger, A. Eisenberge, Nano-engineering block copolymer aggregates for drug delivery, Colloids Surf. B 16 (1999) 3–27. [3] K.B. Thurmond, H. Huang, C.G. Clark, T. Kowalewski, K.L. Wooley, Shell cross-linked polymer micelles: stabilized assemblies with great versatility and potential, Colloids Surf. B 16 (1999) 45–54. [4] X. Shuai, T. Merdan, A.K. Schaper, F. Xi, T. Kissel, Core-cross-linked polymeric micelles as paclitaxel carriers, Bioconjug. Chem. 15 (2004) 441–448. [5] R. Gref, Y. Minamitake, M.T. Peracchia, V. Trubetskoy, V. Torchilin, R. Langer, Biodegradable long-circulating polymeric nanospheres, Science 263 (1994) 1600–1603. [6] F. Alexis, E. Pridgen, L.K. Molnar, O.C. Farokhzad, Factors affecting the clearance and biodistribution of polymeric nanoparticles, Mol. Pharmacol. 5 (2008) 505–515. [7] M. Gong, S. Yang, J.N. Ma, S.P. Zhang, F.M. Winnik, Y.K. Gong, Tunable cell membrane mimetic surfaces prepared with a novel phospholipid polymer, Appl. Surf. Sci. 255 (2008) 555–558. [8] P.B. Huangfu, M. Gong, C. Zhang, S. Yang, J. Zhao, Y.K. Gong, Cell outer membrane mimetic modification of a cross-linked chitosan surface to improve its hemocompatibility, Colloids Surf. B 71 (2009) 268–274. [9] Y.K. Gong, K. Nakashima, Penetration of pyrene and its derivatives into polystyrene latex particles as studied by fluorescence spectroscopy, Chem. Commun. 18 (2001) 1772–1773.
doi:10.1016/j.jconrel.2011.08.099
[1]. Solid lipid nanoparticles (SLNs) offer an attractive means of drug delivery, particularly for poorly water-soluble drugs. SLNs have the same advantages as polymeric nanoparticles, fat emulsions and liposomes. Large scale production will be important for the commercialization of new products [2,3]. The aim of this study was to evaluate the in vitro release characteristics of pueraria flavones loaded solid lipid nanoparticles and its pharmacokinetics after intragastrical administration in rats. Experimental methods Preparative technique. An accurately weighed amount of poloxamer 188 (350 mg) and double distilled water (30 mL) were placed in a standard 100 mL conical flask whose temperature was controlled at 75 ± 2 °C by a circulating water bath. After melting poloxamer 188, 60 mL of ethanol solution containing pueraria flavones (25 mg), lecithin (130 mg) and stearic acid (500 mg) as the lipid phase was slowly injected under stirring at 1000 rpm. The resulting hot emulsion was further stirred for 4 h at 1000 rpm and then concentrated to 30 mL by evaporating ethanol. Solid lipid nanoparticles loaded with pueraria flavones (PF-SLN) were prepared by quickly transferring the hot emulsion (30 mL) to 0–2 °C double distilled water (420 mL) and stirring at 1000 rpm for 1 h. Entrapment efficiency (EE). The entrapment efficiency of pueraria flavones was determined by measuring the concentration of puerarin in the dispersion medium. Ultracentrifugation was carried out at 12,000 rpm for 30 min. Supernatants were dialyzed (0.45 μm) and 0.5 mL filtrate was transferred to a 10 mL volumetric flask and methyl alcohol was added to obtain a constant volume. Samples were analyzed by HPLC. The chromatographic system consisted of a Shimadzu LC-10AT solvent delivery pump equipped with a 20-Al loop and rheodyne sample injector. A Diamonsil C18 (25 cm × 4.6 mm, 5 μm) analytical column was used. The detector used was a SPD-10A VP dual wavelength UV–Visible detector (Shimadzu) operated at 254 nm. Mobile phase was methanol/water (65/35, v/v) and flow rate was 1 mL/min. The EE was determined using the following equation: EEð%Þ ¼
Preparation and pharmacokinetics of solid lipid nanoparticles loaded with pueraria flavones Qingxiang Guan1, Qingtao Guan2, Tianmu Lin1, Jianyuan Yin1 Department of Pharmacy, College of Pharmacy, Jilin University, 1266 Fujin Street, Changchun 130021, China 2 China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun 130033, China E-mail address: [email protected] (Q. Guan). 1
Abstract summary The advantages offered by solid lipid nanoparticles (SLN) include ease of scale up production without the use of organic solvents, use of GRAS listed excipients and a wide spectrum of applications (dermal, oral, intravenous). Moreover, SLN can be used to deliver lipophilic drugs more effectively and to enhance bioavailability. Keywords: Solid lipid nanoparticles, Pueraria flavones, Stearic acid, Pharmacokinetics Introduction Pueraria flavones (PF) are the effective fraction of Pueraria lobata and have several effects such as dilation of the coronaries and brain blood vessels, and can be used to treat hypertension and so on [1]. PF has been widely used for the treatment of coronary heart disease and hypertension, but its poor solubility in water and the gastrointestinal fluid often lead to low dissolution rates and insufficient bioavailability
e25
amount of drug in SLN 100% amount of drug added
In vitro release study. In vitro release studies in vitro were carried out with nanoparticle suspensions within 24 h of preparation. In order to separate free drug, nanoparticle suspensions were centrifuged at 12,000 rpm for 30 min and filtered. The collected nanoparticles were diluted by double distilled water and centrifuged at 12,000 rpm for 30 min and filtered. After the procedure was repeated 3 times, the drug release from SLN in phosphate buffer (pH 6.8) was studied. 5 mL of nanoparticle suspension and 45 mL of phosphate buffer solution (pH 6.8) were transferred into a conical flask with stopper respectively. The conical flasks were placed into a thermostatic shaker at 37 ± 0.5 °C at a rate of 60 times per min. At predetermined time intervals (0, 0.5, 2, 4, 8, 12, 24, 48, 72 h), the medium in the conical flask was completely removed by centrifugation and filtration for analysis and fresh dialysis medium was then added to maintain sink conditions. The filtrate was analyzed by the HPLC method as described above. All operations were carried out in triplicate. Pharmacokinetics and plasma sample analysis. Male Wistar rats (provided by Experimental Animals Centre of Jilin University, China), 250 ± 20 g were used for the oral administration. All animal experiments complied with the requirements of the National Act on the use of experimental animals (People's Republic of China). All the rats were fasted for 12 h before the experiments but had free access to water. A dose of 30 mg/kg of each formulation was administered intragastrically. Control groups received the appropriate vehicles.
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Abstracts / Journal of Controlled Release 152 (2011) e1–e132
Blood samples (0.5 mL) were collected via the orbit at 0, 5, 10, 15, 30, 45, 60, 90, 120, 180, and 300 min after administration and placed into heparinized tubes and separated immediately by centrifugation respectively. After centrifugation, the plasma obtained was stored at −20 °C until analysis. Protein precipitation was carried out with 200 μL plasma by addition of 200 μL methanol and 200 μL 6% hydrochloric acid with the vortex mixer. After centrifugation at 4500 rpm for 15 min, the supernatant was filtered via a millipore filter (0.45 μm). 200 μL of filtrate was injected and analyzed by HPLC as described above. Results and discussion Stearic acid was liquid at the preparation temperature of 75 °C. The solubility of flavonoids was very low, so most of the drug was present in the emulsion droplet formed by stearic acid. After rapid cooling in a water-ice bath solid lipid nanoparticles were formed. More precipitate will be formed and the stability of the system will be significantly decreased if the cooling process lasts too long. The reason for destabilization appears to be the stickiness of the system and the collision of emulsion droplets during solidification. The average entrapment efficiency (EE) was 67.53 ± 0.12%. As the percentage of poloxamer 188 increased, the entrapment efficiency was obviously decreased. This may be due to an increase of solubility of pueraria flavones in the aqueous phase with increasing percentage of poloxamer 188. An increase in the lipid content could reduce the amount of drug transferring from the internal phase into the external phase, which leads to an increase of EE [4]. Sephadex with coarse glucan G-50 was used to separate nanoparticles and free drug, but the separation was not ideal. Moreover, gel filtration takes too much time. According to the literature, SLN suspensions have a high negative charge, so AlCl3 was added to induce the SLN suspension to gelate after which centrifugation at 3000 r/min was carried out. The result was also not ideal. Low-temperature super-speed centrifugation was ultimately chosen to effectively separate nanoparticles and free drug. Release of PF from SLN occurred rapidly in the early stage and then release became slower with an accumulated release of up to 50% in 12 h. The reason for this phenomenon might be attributed to fast release by absorbed PF or PF, precipitated on the surface of the nanoparticles or enrichment of PF in the outer layers of the nanoparticles, which is then followed by slow drug release by matrix erosion. The results also indicated that the majority of the drug was enclosed in nanoparticles while the remainder was encapsulated in colloidal structures, such as micelles or liposomes [5].
using the calibration graph. Pharmacokinetic parameters as obtained from Top fit software are presented in Table 1. As shown in Table 1, plasma clearance kinetics are comparable for PF-SLN and PF. This shows that PF is rapidly cleared from the plasma. Also, the AUC value for PF is lower than that for PF-SLN.
Table 1 Pharmacokinetic parameters after intragastric administration of PF-SLN and PF at a dose of 30 mg/kg of puerarin.
Cmax (ng/mL) tmax (h) AUC0-∞(ng·h/mL) V (L/kg) CL (mL/min)
PF-SLN
PF
822.47 0.5 1581.59 45.54383 319.55
215.45 0.75 579.59 230.15 939.87
Conclusion In this study, SLN loaded with pueraria flavones were successfully prepared using stearic acid as the lipid core by an emulsification/ evaporation–solidification procedure at a low temperature. The adsorption of PF-SLN also altered the pharmacokinetics of PF, as indicated by lower plasma clearance as compared to PF. References [1] W.H. Lin, C.Y. Zhu, W. Chen, F. Shi, Studies on absorption kinetics of puerariae flavones in rats intestineChina J. Chin. Mater. Med. 33 (2008) 164–168. [2] P. Sharma, S. Ganta, W.A. Denny, S. Garg, Formulation and pharmacokinetics of lipid nanoparticles of a chemically sensitive nitrogen mustard derivative: Chlorambucil, Int. J. Pharm. 367 (2009) 187–194. [3] S.H. Zhang, S.C. Shen, Z. Chen, J.X. Yun, K.J. Yao, B.B. Chen, J.Z. Chen, Preparation of solid lipid nanoparticles in co-flowing microchannels, Chem. Eng. J. 144 (2008) 324–328. [4] K.A. Shah, A.A. Date, M.D. Joshi, V.B. Patravale, Solid lipid nanoparticles (SLN) of tretinoin: potential in topical delivery, Int. J. Pharm. 345 (2007) 163–171. [5] D.R. Zhang, T.C. Ren, H.X. Lou, J.H. Zhang, Studies on preparation and property of oridonin solid lipid nanoparticles, Chin. Pharm. J. 39 (2004) 123–126.
doi:10.1016/j.jconrel.2011.08.100
Studies on pH-sensitive micellar structures for sustained drug delivery: Experiments and computer simulations Xin Dong Guo, Li Juan Zhang, Zhi Min Wu, Yu Qian School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China E-mail address: [email protected] (X.D. Guo). Abstract summary Computer simulations were performed to study the microstructures of doxorubicin (DOX) loaded micelles self-assembled from cholesterol conjugated His10Arg10 at different pH conditions. DOX molecules can be efficiently encapsulated in the core of micelles. With the decrease of pH from pHN 6.0 to pH b 6.0, the structure of the micelles changes from dense to more swollen. This structural transformation can facilitate the release of DOX from the core of micelles. All the simulation results are consistent with the experimental results qualitatively. Keywords: Drug delivery, Micelle, pH-sensitive, Amphiphilic, Dissipative particle dynamics
Fig. 1. In vitro release PF from PF-SLN.
Calibration curves were prepared by linear regression analysis of the plot of the peak area against the concentration of puerarin. Results showed that the HPLC method is linearly covering the range of 0.05–1.50 μg/mL (r = 0.999 4, n = 5) with a limit of quantification at 0.05 μg/mL (precision of 7.1% RSD). The concentration of plasma samples was determined from the area of the chromatographic peak
Introduction In recent years, polymeric micelles hold a significant potential as drug delivery vehicles for a wide array of anticancer drugs due to their unique properties, such as high solubility, high drug loading capacity, and low toxicity [1]. Some micelles showed noticeable pHdependent behavior, leading to a quick release at pH 5.0 and a slow release at pH 7.4. Although pH-sensitive micelles have been
scanning electron microscopy measurements. Intramicellar crosslinking enhanced the micelle stability against dilution in aqueous solution, and at the same time, controllable micellar permeability was obtained. Water insoluble model drug ADR was successfully trapped in the hydrophobic core domain of the micelles and showed a sustained and remarkably slower release behavior. The crosslinked micelles prepared from crosslinkable and amphiphilic phospholipid random copolymers with a cell outer membrane mimetic shell could be a promising candidate for prolonged circulating drug delivery carriers, especially for intravenous administration. Acknowledgments This work was supported by the National Natural Science Foundation of China (20774073, 20974087), and NWU Graduate Innovation and Creativity Funds (07YZZ22, 09YZZ46). References [1] G.S. Kwon, K. Kataoka, Polymeric micelles as mew drug carriersAdv. Drug Deliv. Rev. 21 (1996) 107–116. [2] C. Allen, D. Maysinger, A. Eisenberge, Nano-engineering block copolymer aggregates for drug delivery, Colloids Surf. B 16 (1999) 3–27. [3] K.B. Thurmond, H. Huang, C.G. Clark, T. Kowalewski, K.L. Wooley, Shell cross-linked polymer micelles: stabilized assemblies with great versatility and potential, Colloids Surf. B 16 (1999) 45–54. [4] X. Shuai, T. Merdan, A.K. Schaper, F. Xi, T. Kissel, Core-cross-linked polymeric micelles as paclitaxel carriers, Bioconjug. Chem. 15 (2004) 441–448. [5] R. Gref, Y. Minamitake, M.T. Peracchia, V. Trubetskoy, V. Torchilin, R. Langer, Biodegradable long-circulating polymeric nanospheres, Science 263 (1994) 1600–1603. [6] F. Alexis, E. Pridgen, L.K. Molnar, O.C. Farokhzad, Factors affecting the clearance and biodistribution of polymeric nanoparticles, Mol. Pharmacol. 5 (2008) 505–515. [7] M. Gong, S. Yang, J.N. Ma, S.P. Zhang, F.M. Winnik, Y.K. Gong, Tunable cell membrane mimetic surfaces prepared with a novel phospholipid polymer, Appl. Surf. Sci. 255 (2008) 555–558. [8] P.B. Huangfu, M. Gong, C. Zhang, S. Yang, J. Zhao, Y.K. Gong, Cell outer membrane mimetic modification of a cross-linked chitosan surface to improve its hemocompatibility, Colloids Surf. B 71 (2009) 268–274. [9] Y.K. Gong, K. Nakashima, Penetration of pyrene and its derivatives into polystyrene latex particles as studied by fluorescence spectroscopy, Chem. Commun. 18 (2001) 1772–1773.
doi:10.1016/j.jconrel.2011.08.099
[1]. Solid lipid nanoparticles (SLNs) offer an attractive means of drug delivery, particularly for poorly water-soluble drugs. SLNs have the same advantages as polymeric nanoparticles, fat emulsions and liposomes. Large scale production will be important for the commercialization of new products [2,3]. The aim of this study was to evaluate the in vitro release characteristics of pueraria flavones loaded solid lipid nanoparticles and its pharmacokinetics after intragastrical administration in rats. Experimental methods Preparative technique. An accurately weighed amount of poloxamer 188 (350 mg) and double distilled water (30 mL) were placed in a standard 100 mL conical flask whose temperature was controlled at 75 ± 2 °C by a circulating water bath. After melting poloxamer 188, 60 mL of ethanol solution containing pueraria flavones (25 mg), lecithin (130 mg) and stearic acid (500 mg) as the lipid phase was slowly injected under stirring at 1000 rpm. The resulting hot emulsion was further stirred for 4 h at 1000 rpm and then concentrated to 30 mL by evaporating ethanol. Solid lipid nanoparticles loaded with pueraria flavones (PF-SLN) were prepared by quickly transferring the hot emulsion (30 mL) to 0–2 °C double distilled water (420 mL) and stirring at 1000 rpm for 1 h. Entrapment efficiency (EE). The entrapment efficiency of pueraria flavones was determined by measuring the concentration of puerarin in the dispersion medium. Ultracentrifugation was carried out at 12,000 rpm for 30 min. Supernatants were dialyzed (0.45 μm) and 0.5 mL filtrate was transferred to a 10 mL volumetric flask and methyl alcohol was added to obtain a constant volume. Samples were analyzed by HPLC. The chromatographic system consisted of a Shimadzu LC-10AT solvent delivery pump equipped with a 20-Al loop and rheodyne sample injector. A Diamonsil C18 (25 cm × 4.6 mm, 5 μm) analytical column was used. The detector used was a SPD-10A VP dual wavelength UV–Visible detector (Shimadzu) operated at 254 nm. Mobile phase was methanol/water (65/35, v/v) and flow rate was 1 mL/min. The EE was determined using the following equation: EEð%Þ ¼
Preparation and pharmacokinetics of solid lipid nanoparticles loaded with pueraria flavones Qingxiang Guan1, Qingtao Guan2, Tianmu Lin1, Jianyuan Yin1 Department of Pharmacy, College of Pharmacy, Jilin University, 1266 Fujin Street, Changchun 130021, China 2 China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun 130033, China E-mail address: [email protected] (Q. Guan). 1
Abstract summary The advantages offered by solid lipid nanoparticles (SLN) include ease of scale up production without the use of organic solvents, use of GRAS listed excipients and a wide spectrum of applications (dermal, oral, intravenous). Moreover, SLN can be used to deliver lipophilic drugs more effectively and to enhance bioavailability. Keywords: Solid lipid nanoparticles, Pueraria flavones, Stearic acid, Pharmacokinetics Introduction Pueraria flavones (PF) are the effective fraction of Pueraria lobata and have several effects such as dilation of the coronaries and brain blood vessels, and can be used to treat hypertension and so on [1]. PF has been widely used for the treatment of coronary heart disease and hypertension, but its poor solubility in water and the gastrointestinal fluid often lead to low dissolution rates and insufficient bioavailability
e25
amount of drug in SLN 100% amount of drug added
In vitro release study. In vitro release studies in vitro were carried out with nanoparticle suspensions within 24 h of preparation. In order to separate free drug, nanoparticle suspensions were centrifuged at 12,000 rpm for 30 min and filtered. The collected nanoparticles were diluted by double distilled water and centrifuged at 12,000 rpm for 30 min and filtered. After the procedure was repeated 3 times, the drug release from SLN in phosphate buffer (pH 6.8) was studied. 5 mL of nanoparticle suspension and 45 mL of phosphate buffer solution (pH 6.8) were transferred into a conical flask with stopper respectively. The conical flasks were placed into a thermostatic shaker at 37 ± 0.5 °C at a rate of 60 times per min. At predetermined time intervals (0, 0.5, 2, 4, 8, 12, 24, 48, 72 h), the medium in the conical flask was completely removed by centrifugation and filtration for analysis and fresh dialysis medium was then added to maintain sink conditions. The filtrate was analyzed by the HPLC method as described above. All operations were carried out in triplicate. Pharmacokinetics and plasma sample analysis. Male Wistar rats (provided by Experimental Animals Centre of Jilin University, China), 250 ± 20 g were used for the oral administration. All animal experiments complied with the requirements of the National Act on the use of experimental animals (People's Republic of China). All the rats were fasted for 12 h before the experiments but had free access to water. A dose of 30 mg/kg of each formulation was administered intragastrically. Control groups received the appropriate vehicles.
e26
Abstracts / Journal of Controlled Release 152 (2011) e1–e132
Blood samples (0.5 mL) were collected via the orbit at 0, 5, 10, 15, 30, 45, 60, 90, 120, 180, and 300 min after administration and placed into heparinized tubes and separated immediately by centrifugation respectively. After centrifugation, the plasma obtained was stored at −20 °C until analysis. Protein precipitation was carried out with 200 μL plasma by addition of 200 μL methanol and 200 μL 6% hydrochloric acid with the vortex mixer. After centrifugation at 4500 rpm for 15 min, the supernatant was filtered via a millipore filter (0.45 μm). 200 μL of filtrate was injected and analyzed by HPLC as described above. Results and discussion Stearic acid was liquid at the preparation temperature of 75 °C. The solubility of flavonoids was very low, so most of the drug was present in the emulsion droplet formed by stearic acid. After rapid cooling in a water-ice bath solid lipid nanoparticles were formed. More precipitate will be formed and the stability of the system will be significantly decreased if the cooling process lasts too long. The reason for destabilization appears to be the stickiness of the system and the collision of emulsion droplets during solidification. The average entrapment efficiency (EE) was 67.53 ± 0.12%. As the percentage of poloxamer 188 increased, the entrapment efficiency was obviously decreased. This may be due to an increase of solubility of pueraria flavones in the aqueous phase with increasing percentage of poloxamer 188. An increase in the lipid content could reduce the amount of drug transferring from the internal phase into the external phase, which leads to an increase of EE [4]. Sephadex with coarse glucan G-50 was used to separate nanoparticles and free drug, but the separation was not ideal. Moreover, gel filtration takes too much time. According to the literature, SLN suspensions have a high negative charge, so AlCl3 was added to induce the SLN suspension to gelate after which centrifugation at 3000 r/min was carried out. The result was also not ideal. Low-temperature super-speed centrifugation was ultimately chosen to effectively separate nanoparticles and free drug. Release of PF from SLN occurred rapidly in the early stage and then release became slower with an accumulated release of up to 50% in 12 h. The reason for this phenomenon might be attributed to fast release by absorbed PF or PF, precipitated on the surface of the nanoparticles or enrichment of PF in the outer layers of the nanoparticles, which is then followed by slow drug release by matrix erosion. The results also indicated that the majority of the drug was enclosed in nanoparticles while the remainder was encapsulated in colloidal structures, such as micelles or liposomes [5].
using the calibration graph. Pharmacokinetic parameters as obtained from Top fit software are presented in Table 1. As shown in Table 1, plasma clearance kinetics are comparable for PF-SLN and PF. This shows that PF is rapidly cleared from the plasma. Also, the AUC value for PF is lower than that for PF-SLN.
Table 1 Pharmacokinetic parameters after intragastric administration of PF-SLN and PF at a dose of 30 mg/kg of puerarin.
Cmax (ng/mL) tmax (h) AUC0-∞(ng·h/mL) V (L/kg) CL (mL/min)
PF-SLN
PF
822.47 0.5 1581.59 45.54383 319.55
215.45 0.75 579.59 230.15 939.87
Conclusion In this study, SLN loaded with pueraria flavones were successfully prepared using stearic acid as the lipid core by an emulsification/ evaporation–solidification procedure at a low temperature. The adsorption of PF-SLN also altered the pharmacokinetics of PF, as indicated by lower plasma clearance as compared to PF. References [1] W.H. Lin, C.Y. Zhu, W. Chen, F. Shi, Studies on absorption kinetics of puerariae flavones in rats intestineChina J. Chin. Mater. Med. 33 (2008) 164–168. [2] P. Sharma, S. Ganta, W.A. Denny, S. Garg, Formulation and pharmacokinetics of lipid nanoparticles of a chemically sensitive nitrogen mustard derivative: Chlorambucil, Int. J. Pharm. 367 (2009) 187–194. [3] S.H. Zhang, S.C. Shen, Z. Chen, J.X. Yun, K.J. Yao, B.B. Chen, J.Z. Chen, Preparation of solid lipid nanoparticles in co-flowing microchannels, Chem. Eng. J. 144 (2008) 324–328. [4] K.A. Shah, A.A. Date, M.D. Joshi, V.B. Patravale, Solid lipid nanoparticles (SLN) of tretinoin: potential in topical delivery, Int. J. Pharm. 345 (2007) 163–171. [5] D.R. Zhang, T.C. Ren, H.X. Lou, J.H. Zhang, Studies on preparation and property of oridonin solid lipid nanoparticles, Chin. Pharm. J. 39 (2004) 123–126.
doi:10.1016/j.jconrel.2011.08.100
Studies on pH-sensitive micellar structures for sustained drug delivery: Experiments and computer simulations Xin Dong Guo, Li Juan Zhang, Zhi Min Wu, Yu Qian School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China E-mail address: [email protected] (X.D. Guo). Abstract summary Computer simulations were performed to study the microstructures of doxorubicin (DOX) loaded micelles self-assembled from cholesterol conjugated His10Arg10 at different pH conditions. DOX molecules can be efficiently encapsulated in the core of micelles. With the decrease of pH from pHN 6.0 to pH b 6.0, the structure of the micelles changes from dense to more swollen. This structural transformation can facilitate the release of DOX from the core of micelles. All the simulation results are consistent with the experimental results qualitatively. Keywords: Drug delivery, Micelle, pH-sensitive, Amphiphilic, Dissipative particle dynamics
Fig. 1. In vitro release PF from PF-SLN.
Calibration curves were prepared by linear regression analysis of the plot of the peak area against the concentration of puerarin. Results showed that the HPLC method is linearly covering the range of 0.05–1.50 μg/mL (r = 0.999 4, n = 5) with a limit of quantification at 0.05 μg/mL (precision of 7.1% RSD). The concentration of plasma samples was determined from the area of the chromatographic peak
Introduction In recent years, polymeric micelles hold a significant potential as drug delivery vehicles for a wide array of anticancer drugs due to their unique properties, such as high solubility, high drug loading capacity, and low toxicity [1]. Some micelles showed noticeable pHdependent behavior, leading to a quick release at pH 5.0 and a slow release at pH 7.4. Although pH-sensitive micelles have been