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Relationship between N,N -dialkyl chitosan monolayer and corresponding vesicle
Journal of Colloid and Interface Science 311 (2007) 285–288 www.elsevier.com/locate/jcis
Relationship between N ,N -dialkyl chitosan monolayer and corresponding vesicle Mingchun Li ∗ , Sheng Su, Meihua Xin, Yaozu Liao College of Materials Science and Engineering, Huaqiao University, Quanzhou, Fujian 362021, PR China Received 24 October 2006; accepted 30 December 2006 Available online 6 April 2007
Abstract The properties of N ,N -dialkyl chitosan monolayers and corresponding vesicles have been studied by LB technique and drug-release experiment. With increasing molecular weight of chitosan backbone and/or length of alkyl chain, both the compressibility and collapse pressure of N ,N -dialkyl chitosan monolayer are enhanced. The experiments on drug-release behavior of N ,N -dialkyl chitosan vesicles show that the drug-release rate and the equilibrium drug-release ratio are decreased with increasing the compressibility of corresponding monolayer. It is worth noticing that there is a linear relationship between the compressibility of N ,N -dialkyl chitosan monolayers and the equilibrium drug-release ratio of the vesicles. © 2007 Elsevier Inc. All rights reserved. Keywords: N ,N -Dialkyl chitosan; Monolayer; Compressibility; Vesicle; Drug-release
1. Introduction Vesicles are self-assembled colloidal particles that occur naturally and can be prepared artificially [1]. Their inimitable structures give them broad usage in mimetic research, gene delivery, and controlled drug-release [2–7]. Because of their broad usage, self-assembled vesicles have received close attention in recent decades. Israelachvili and his co-workers introduced the concept of the shape parameter, which is very useful for a qualitative understanding of the topology of surfactant aggregates with different surfactant compositions [8]. Helfrich and his co-workers established the liquid crystal theory of biomembranes and educed the general shape equation of vesicles, which made it possible to determine certain physical properties of vesicles [9]. However, the microscopic size of vesicles makes them difficult to study in common experimental ways, which hinders the development of vesicles. It is believed that many important phenomena that occur in vesicles can be elucidated by experiments on the monolayer at an interface. Therefore, many researches focused on establishing monolayer–vesicle correspondence theory [10–13]. Al* Corresponding author. Fax: +86 0595 2268 6969.
E-mail address: [email protected] (M. Li). 0021-9797/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jcis.2006.12.082
though different arguments remain, a common point of view has been met that the surface pressure of monolayers and vesicles is equal under conditions of equal molecular density and temperature [12,13]. This conclusion makes it possible to study selfassembled vesicle by investigating the pressure–area isotherms of corresponding monolayer. One of the most important parameters of vesicle is their membrane permeability, which is mainly influenced by the molecular packing of the building block materials [14]. Due to the microscopic size of vesicles, few experimental technologies enable investigation of the molecular packing behavior of vesicles. In the present work, we attempt to learn the molecular packing behavior of vesicles by using monolayers as a model. A comparative study of N ,N -dialkyl chitosan monolayers and their corresponding vesicles has been carried out. The relationship between monolayers and vesicles is thereafter discussed. 2. Materials and methods 2.1. Preparation of N ,N -dialkyl chitosan N ,N -Dioctyl, -didecyl, and -didodecyl chitosans are synthesized by the method of reductive alkylation shown in Scheme 1, performed as previous report [15].
286
M. Li et al. / Journal of Colloid and Interface Science 311 (2007) 285–288
Scheme 1. The synthetic route of N ,N -dialkyl chitosan.
2.2. Surface pressure–area isotherms of N ,N -dialkyl chitosan monolayers
3. Results and discussion 3.1. Properties of N ,N -dialkyl chitosan monolayers
Surface pressure–area isotherms of N ,N -dialkyl chitosan monolayers are studied on a KSV-5000 system (KSV Instruments Ltd., Finland) installed in a laminar flow hood. The trough and barriers are made of PTFE and the trough area is 510 × 150 mm. Pure water without any additives filtered by Milli-Q (surface tension 72 mN/m, Millipore Ltd., USA) is used as the liquid surface phase in all experiments. The N ,N dialkyl chitosans are dissolved in chloroform to give concentrations of 10−3 mol/L. 30 µl of the solutions are spread onto the air–water interface. The pressure–area isotherms are determined by the Wilhelmy plate method with compression of 10 mm/min over a period of 30 min. Experiments are carried out at constant temperature of 25 ◦ C controlled by water circulation and repeated three times to establish reproducibility. 2.3. Preparation and drug-release behaviors of N ,N -dialkyl chitosan self-assembled vesicles N,N -Dialkyl chitosan self-assembled vesicles are prepared by a reversed-phase evaporation method, performed as follows [15]: 8 ml of vitamin B12 (4 mg/ml, Sino-America Biotechnology) is dispersed in 24 ml of a solution of N ,N dialkyl chitosan in chloroform with a concentration of 0.2 mol/L. The suspensions are thereafter sonicated for 25 min in a bath sonicator (Cole–Parmer) to form a water-in-oil emulsion. The solvent is subsequently removed by rotation evaporator. The vesicles are finally obtained after intensively ultrasonicating the sample for 5 min. Unentrapped vitamin B12 is removed by ultracentrifugation (Kendro). The size distributions of vesicles are measured with a Zetasizer-3000 photon correlation spectrometer (Malvern). Vesicles containing vitamin B12 are placed in 1 ml pure water and poured into dialysis tubing and the latter is placed in 25 ml pure water. At different time intervals, aliquots of the medium are replaced with the same amount of fresh water. B12 concentration is analyzed by UV spectrophotometry (Shimadzu) at λmax = 361 nm. The amount of vitamin B12 released was determined by extrapolation from the corresponding calibration curve (C = 0.05829A − 0.00036).
π–A isotherms of N ,N -dilauryl chitosan pentamer have been studied in a previous report [16]. π–A isotherms of N ,N dialkyl chitosan monolayers are shown in Fig. 1. For further investigation, we calculate the compressibility modulus of monolayers (defined as Cs−1 = −A(dπ/dA) [17]), which represent the elasticity of the monolayer. This value depends on the state of the film in such a way that the larger the value, the more rigid and less compressible the monolayer. Cs−1 –A curves of N ,N dialkyl chitosan monolayers are shown in Fig. 2. Table 1 shows some characteristics of N ,N -dialkyl chitosan monolayers. 3.1.1. Effect of backbone molecular weight on monolayer As shown in Fig. 1, both the collapse pressure and the collapse area increase with increasing backbone molecular weight, whereas the extrapolated area decreases. These trends indicate that N ,N -dialkyl derivatives with higher backbone molecular weight tend to form more chain-ordered, condensed monolayers. According to the Cs−1 –A curves, the compressibility modulus of lower backbone molecular weight N ,N -dialkyl chitosan
Fig. 1. Surface pressure–area isotherms for N ,N -dialkyl chitosan monolayers. Symbols have the same meaning as shown in Table 1.
M. Li et al. / Journal of Colloid and Interface Science 311 (2007) 285–288
287
Fig. 2. Compressibility modulus–area curves for N ,N -dialkyl chitosan monolayers. Symbols have the same meaning as shown in Table 1.
Fig. 3. Drug release behavior of different N ,N -dialkyl chitosan self-assembled vesicles. Symbols have the same meaning as shown in Table 1.
achieved two peak values that indicate obvious transition from liquid-expanded (LE) to liquid-condensed (LC). With increasing molecular weight of chitosan backbone, the compressibility modulus of the N,N -dialkyl chitosan monolayer is enhanced. The experimental results imply that N ,N -dialkyl chitosan with higher backbone molecular weight tends to form rigid and compact monolayers. This may be due to the entanglement of its macromolecular chain.
following plateau phase. Drug-release rates of vesicles made from longer alkyl chains and/or larger backbone molecular weight of N ,N -dialkyl chitosan are lower than others, and equilibrium drug-release ratios as well. The drug-release behavior of N ,N -dialkyl chitosan vesicles agrees well with the predictions discussed in the monolayer study section.
3.1.2. Effect of side chain on monolayer π–A isotherms of N ,N -dialkyl chitosan monolayers with the same backbone molecular weight are similar. Both collapse pressure and extrapolated areas increase in the order of increasing length of alkyl chains. The compressibility modulus implies that rigidity of monolayer increases slightly with lengthened alkyl side-chain. These could be caused by the hydrophobic interaction of the long alkyl side-chain. According to the properties of N ,N -dialkyl chitosan monolayers, it is predicted that N ,N -dialkyl chitosan with higher backbone molecular weight and/or longer side-chains may form vesicles with more compact membrane structure. 3.2. Drug release behaviors of N ,N -dialkyl chitosan vesicles PCS measurements show that the diameters of N ,N -dialkyl chitosan self-assembled vesicles are mainly between 100 and 200 nm. The drug release behaviors of N ,N -dialkyl chitosan vesicles are shown in Fig. 3. They are characterized by diphasic drug release kinetics, including the initial burst phase and the
3.3. Correspondence of monolayer and vesicle membrane N ,N -dialkyl chitosans are stable in neutral water. The drug release mechanism of N ,N -dialkyl chitosan vesicles may be attributed to the influence of membrane permeability. Fig. 4 illustrates the relationships between monolayer compressibility and drug-release equilibrium ratio of the corresponding vesicles. Results indicates that the drug-release equilibrium ratio of self-assembled vesicles is decreased with increasing compressibility of the corresponding material monolayer, which has a linear relationship. This finding indicates that the tightness of the vesicle membrane can be predicted through the properties of the corresponding monolayer. Besides, this is useful in preparing N ,N -dialkyl chitosan vesicles with controlled drug-release behavior. Furthermore, it may be helpful in building up a theoretical relationship between monolayers and vesicles. 4. Conclusion In this work, the properties of N ,N -dialkyl chitosan monolayers and the corresponding vesicles have been investigated.
Table 1 Collapse pressure (πc ), extrapolated area (Aex ), and compressibility modulus (Cs−1 ) for N ,N -dialkyl chitosan monolayers Cs−1 (mN/m)
Aldehyde used
Symbol
πc (mN/m)
Aex (Å2 )
3000
Octylaldehyde Decylaldehyde Dodecylaldehyde
a1 b1 c1
37.3 39.2 41.6
74.9 81.3 90.0
88.5 94.2 96.4
10,000
Octylaldehyde Decylaldehyde Dodecylaldehyde
a2 b2 c2
38.9 41.7 43.5
73.7 80.0 83.4
112.4 143.3 165.1
Molecular weight of chitosan (Da)
288
M. Li et al. / Journal of Colloid and Interface Science 311 (2007) 285–288
in building monolayer–bilayer vesicle correspondence theory and developing drug-release behavior controlled vesicles. Acknowledgments This research has been supported by the National Natural Science Foundation of China (No. 20274013), a Key Project of the Fujian Provincial Science and Technology (20021004), and the Fujian Provincial Science Foundation of China (C0310009 and E0540001). References
Fig. 4. Relationships between monolayers and corresponding vesicles. Symbols have the same meaning as shown in Table 1.
With increasing backbone molecular weight and/or length of alkyl chain, the rigidities of N ,N -dialkyl chitosan monolayers are enhanced. The longer the alkyl chain and/or the larger the backbone molecular weight of chitosan, the slower the drugrelease rate of chitosan-based vesicles is, as well as the equilibrium drug-release ratio. Experimental results indicate that the equilibrium drug-release ratios of N ,N -dialkyl chitosan vesicles have a linear relationship with the compressibility of the corresponding monolayer. This finding indicates that the tightness of the vesicle membrane can be predicted through the properties of the corresponding monolayer. This may be useful
[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]
D.D. Lasic, Trends Biotechnol. 16 (1998) 307. H. Li, J.H. Song, J.S. Park, K. Han, Int. J. Pharm. 258 (1–2) (2003) 11. P. Sapra, T.M. Allen, Prog. Lipid Res. 42 (5) (2003) 439. A. Gürsoy, E. Kut, C. Sumru, Int. J. Pharm. 271 (1–2) (2004) 115. Y. Hattori, S. Kawakami, S. Suzuki, F. Yamashita, et al., Biochem. Biophys. Res. Commun. 317 (4) (2004) 992. B. Silva, M. Neila, S. Caligiorne, et al., J. Controll. Rel. 95 (2) (2004) 301. A. Manosroi, K. Podjanasoonthon, J. Manosroi, Int. J. Pharm. 235 (1–2) (2002) 61. J.N. Israelachvili, Colloids Surf. A 91 (1994) 1. Z.C. Ou Yang, W. Helfrich, Phys. Rev. Lett. 59 (1987) 2486. F. Jähnig, Biophys. J. 46 (1984) 687. S.S. Feng, Langmuir 15 (1999) 998. S.S. Feng, Langmuir 22 (2006) 2920. D. Mash, Langmuir 22 (2006) 2916. D.E. Discher, A. Eisenberg, Science 297 (2002) 967. M. Li, M. Xin, Des. Monomers Polym. 9 (2006) 89. M. Li, M. Xin, T. Miyashita, Polym. Int. 51 (2002) 889. S.L. Murov, I. Carmichel, G.L. Hug, Handbook of Photochemistry, Dekker, New York, 1993, p. 89.
Relationship between N ,N -dialkyl chitosan monolayer and corresponding vesicle Mingchun Li ∗ , Sheng Su, Meihua Xin, Yaozu Liao College of Materials Science and Engineering, Huaqiao University, Quanzhou, Fujian 362021, PR China Received 24 October 2006; accepted 30 December 2006 Available online 6 April 2007
Abstract The properties of N ,N -dialkyl chitosan monolayers and corresponding vesicles have been studied by LB technique and drug-release experiment. With increasing molecular weight of chitosan backbone and/or length of alkyl chain, both the compressibility and collapse pressure of N ,N -dialkyl chitosan monolayer are enhanced. The experiments on drug-release behavior of N ,N -dialkyl chitosan vesicles show that the drug-release rate and the equilibrium drug-release ratio are decreased with increasing the compressibility of corresponding monolayer. It is worth noticing that there is a linear relationship between the compressibility of N ,N -dialkyl chitosan monolayers and the equilibrium drug-release ratio of the vesicles. © 2007 Elsevier Inc. All rights reserved. Keywords: N ,N -Dialkyl chitosan; Monolayer; Compressibility; Vesicle; Drug-release
1. Introduction Vesicles are self-assembled colloidal particles that occur naturally and can be prepared artificially [1]. Their inimitable structures give them broad usage in mimetic research, gene delivery, and controlled drug-release [2–7]. Because of their broad usage, self-assembled vesicles have received close attention in recent decades. Israelachvili and his co-workers introduced the concept of the shape parameter, which is very useful for a qualitative understanding of the topology of surfactant aggregates with different surfactant compositions [8]. Helfrich and his co-workers established the liquid crystal theory of biomembranes and educed the general shape equation of vesicles, which made it possible to determine certain physical properties of vesicles [9]. However, the microscopic size of vesicles makes them difficult to study in common experimental ways, which hinders the development of vesicles. It is believed that many important phenomena that occur in vesicles can be elucidated by experiments on the monolayer at an interface. Therefore, many researches focused on establishing monolayer–vesicle correspondence theory [10–13]. Al* Corresponding author. Fax: +86 0595 2268 6969.
E-mail address: [email protected] (M. Li). 0021-9797/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jcis.2006.12.082
though different arguments remain, a common point of view has been met that the surface pressure of monolayers and vesicles is equal under conditions of equal molecular density and temperature [12,13]. This conclusion makes it possible to study selfassembled vesicle by investigating the pressure–area isotherms of corresponding monolayer. One of the most important parameters of vesicle is their membrane permeability, which is mainly influenced by the molecular packing of the building block materials [14]. Due to the microscopic size of vesicles, few experimental technologies enable investigation of the molecular packing behavior of vesicles. In the present work, we attempt to learn the molecular packing behavior of vesicles by using monolayers as a model. A comparative study of N ,N -dialkyl chitosan monolayers and their corresponding vesicles has been carried out. The relationship between monolayers and vesicles is thereafter discussed. 2. Materials and methods 2.1. Preparation of N ,N -dialkyl chitosan N ,N -Dioctyl, -didecyl, and -didodecyl chitosans are synthesized by the method of reductive alkylation shown in Scheme 1, performed as previous report [15].
286
M. Li et al. / Journal of Colloid and Interface Science 311 (2007) 285–288
Scheme 1. The synthetic route of N ,N -dialkyl chitosan.
2.2. Surface pressure–area isotherms of N ,N -dialkyl chitosan monolayers
3. Results and discussion 3.1. Properties of N ,N -dialkyl chitosan monolayers
Surface pressure–area isotherms of N ,N -dialkyl chitosan monolayers are studied on a KSV-5000 system (KSV Instruments Ltd., Finland) installed in a laminar flow hood. The trough and barriers are made of PTFE and the trough area is 510 × 150 mm. Pure water without any additives filtered by Milli-Q (surface tension 72 mN/m, Millipore Ltd., USA) is used as the liquid surface phase in all experiments. The N ,N dialkyl chitosans are dissolved in chloroform to give concentrations of 10−3 mol/L. 30 µl of the solutions are spread onto the air–water interface. The pressure–area isotherms are determined by the Wilhelmy plate method with compression of 10 mm/min over a period of 30 min. Experiments are carried out at constant temperature of 25 ◦ C controlled by water circulation and repeated three times to establish reproducibility. 2.3. Preparation and drug-release behaviors of N ,N -dialkyl chitosan self-assembled vesicles N,N -Dialkyl chitosan self-assembled vesicles are prepared by a reversed-phase evaporation method, performed as follows [15]: 8 ml of vitamin B12 (4 mg/ml, Sino-America Biotechnology) is dispersed in 24 ml of a solution of N ,N dialkyl chitosan in chloroform with a concentration of 0.2 mol/L. The suspensions are thereafter sonicated for 25 min in a bath sonicator (Cole–Parmer) to form a water-in-oil emulsion. The solvent is subsequently removed by rotation evaporator. The vesicles are finally obtained after intensively ultrasonicating the sample for 5 min. Unentrapped vitamin B12 is removed by ultracentrifugation (Kendro). The size distributions of vesicles are measured with a Zetasizer-3000 photon correlation spectrometer (Malvern). Vesicles containing vitamin B12 are placed in 1 ml pure water and poured into dialysis tubing and the latter is placed in 25 ml pure water. At different time intervals, aliquots of the medium are replaced with the same amount of fresh water. B12 concentration is analyzed by UV spectrophotometry (Shimadzu) at λmax = 361 nm. The amount of vitamin B12 released was determined by extrapolation from the corresponding calibration curve (C = 0.05829A − 0.00036).
π–A isotherms of N ,N -dilauryl chitosan pentamer have been studied in a previous report [16]. π–A isotherms of N ,N dialkyl chitosan monolayers are shown in Fig. 1. For further investigation, we calculate the compressibility modulus of monolayers (defined as Cs−1 = −A(dπ/dA) [17]), which represent the elasticity of the monolayer. This value depends on the state of the film in such a way that the larger the value, the more rigid and less compressible the monolayer. Cs−1 –A curves of N ,N dialkyl chitosan monolayers are shown in Fig. 2. Table 1 shows some characteristics of N ,N -dialkyl chitosan monolayers. 3.1.1. Effect of backbone molecular weight on monolayer As shown in Fig. 1, both the collapse pressure and the collapse area increase with increasing backbone molecular weight, whereas the extrapolated area decreases. These trends indicate that N ,N -dialkyl derivatives with higher backbone molecular weight tend to form more chain-ordered, condensed monolayers. According to the Cs−1 –A curves, the compressibility modulus of lower backbone molecular weight N ,N -dialkyl chitosan
Fig. 1. Surface pressure–area isotherms for N ,N -dialkyl chitosan monolayers. Symbols have the same meaning as shown in Table 1.
M. Li et al. / Journal of Colloid and Interface Science 311 (2007) 285–288
287
Fig. 2. Compressibility modulus–area curves for N ,N -dialkyl chitosan monolayers. Symbols have the same meaning as shown in Table 1.
Fig. 3. Drug release behavior of different N ,N -dialkyl chitosan self-assembled vesicles. Symbols have the same meaning as shown in Table 1.
achieved two peak values that indicate obvious transition from liquid-expanded (LE) to liquid-condensed (LC). With increasing molecular weight of chitosan backbone, the compressibility modulus of the N,N -dialkyl chitosan monolayer is enhanced. The experimental results imply that N ,N -dialkyl chitosan with higher backbone molecular weight tends to form rigid and compact monolayers. This may be due to the entanglement of its macromolecular chain.
following plateau phase. Drug-release rates of vesicles made from longer alkyl chains and/or larger backbone molecular weight of N ,N -dialkyl chitosan are lower than others, and equilibrium drug-release ratios as well. The drug-release behavior of N ,N -dialkyl chitosan vesicles agrees well with the predictions discussed in the monolayer study section.
3.1.2. Effect of side chain on monolayer π–A isotherms of N ,N -dialkyl chitosan monolayers with the same backbone molecular weight are similar. Both collapse pressure and extrapolated areas increase in the order of increasing length of alkyl chains. The compressibility modulus implies that rigidity of monolayer increases slightly with lengthened alkyl side-chain. These could be caused by the hydrophobic interaction of the long alkyl side-chain. According to the properties of N ,N -dialkyl chitosan monolayers, it is predicted that N ,N -dialkyl chitosan with higher backbone molecular weight and/or longer side-chains may form vesicles with more compact membrane structure. 3.2. Drug release behaviors of N ,N -dialkyl chitosan vesicles PCS measurements show that the diameters of N ,N -dialkyl chitosan self-assembled vesicles are mainly between 100 and 200 nm. The drug release behaviors of N ,N -dialkyl chitosan vesicles are shown in Fig. 3. They are characterized by diphasic drug release kinetics, including the initial burst phase and the
3.3. Correspondence of monolayer and vesicle membrane N ,N -dialkyl chitosans are stable in neutral water. The drug release mechanism of N ,N -dialkyl chitosan vesicles may be attributed to the influence of membrane permeability. Fig. 4 illustrates the relationships between monolayer compressibility and drug-release equilibrium ratio of the corresponding vesicles. Results indicates that the drug-release equilibrium ratio of self-assembled vesicles is decreased with increasing compressibility of the corresponding material monolayer, which has a linear relationship. This finding indicates that the tightness of the vesicle membrane can be predicted through the properties of the corresponding monolayer. Besides, this is useful in preparing N ,N -dialkyl chitosan vesicles with controlled drug-release behavior. Furthermore, it may be helpful in building up a theoretical relationship between monolayers and vesicles. 4. Conclusion In this work, the properties of N ,N -dialkyl chitosan monolayers and the corresponding vesicles have been investigated.
Table 1 Collapse pressure (πc ), extrapolated area (Aex ), and compressibility modulus (Cs−1 ) for N ,N -dialkyl chitosan monolayers Cs−1 (mN/m)
Aldehyde used
Symbol
πc (mN/m)
Aex (Å2 )
3000
Octylaldehyde Decylaldehyde Dodecylaldehyde
a1 b1 c1
37.3 39.2 41.6
74.9 81.3 90.0
88.5 94.2 96.4
10,000
Octylaldehyde Decylaldehyde Dodecylaldehyde
a2 b2 c2
38.9 41.7 43.5
73.7 80.0 83.4
112.4 143.3 165.1
Molecular weight of chitosan (Da)
288
M. Li et al. / Journal of Colloid and Interface Science 311 (2007) 285–288
in building monolayer–bilayer vesicle correspondence theory and developing drug-release behavior controlled vesicles. Acknowledgments This research has been supported by the National Natural Science Foundation of China (No. 20274013), a Key Project of the Fujian Provincial Science and Technology (20021004), and the Fujian Provincial Science Foundation of China (C0310009 and E0540001). References
Fig. 4. Relationships between monolayers and corresponding vesicles. Symbols have the same meaning as shown in Table 1.
With increasing backbone molecular weight and/or length of alkyl chain, the rigidities of N ,N -dialkyl chitosan monolayers are enhanced. The longer the alkyl chain and/or the larger the backbone molecular weight of chitosan, the slower the drugrelease rate of chitosan-based vesicles is, as well as the equilibrium drug-release ratio. Experimental results indicate that the equilibrium drug-release ratios of N ,N -dialkyl chitosan vesicles have a linear relationship with the compressibility of the corresponding monolayer. This finding indicates that the tightness of the vesicle membrane can be predicted through the properties of the corresponding monolayer. This may be useful
[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]
D.D. Lasic, Trends Biotechnol. 16 (1998) 307. H. Li, J.H. Song, J.S. Park, K. Han, Int. J. Pharm. 258 (1–2) (2003) 11. P. Sapra, T.M. Allen, Prog. Lipid Res. 42 (5) (2003) 439. A. Gürsoy, E. Kut, C. Sumru, Int. J. Pharm. 271 (1–2) (2004) 115. Y. Hattori, S. Kawakami, S. Suzuki, F. Yamashita, et al., Biochem. Biophys. Res. Commun. 317 (4) (2004) 992. B. Silva, M. Neila, S. Caligiorne, et al., J. Controll. Rel. 95 (2) (2004) 301. A. Manosroi, K. Podjanasoonthon, J. Manosroi, Int. J. Pharm. 235 (1–2) (2002) 61. J.N. Israelachvili, Colloids Surf. A 91 (1994) 1. Z.C. Ou Yang, W. Helfrich, Phys. Rev. Lett. 59 (1987) 2486. F. Jähnig, Biophys. J. 46 (1984) 687. S.S. Feng, Langmuir 15 (1999) 998. S.S. Feng, Langmuir 22 (2006) 2920. D. Mash, Langmuir 22 (2006) 2916. D.E. Discher, A. Eisenberg, Science 297 (2002) 967. M. Li, M. Xin, Des. Monomers Polym. 9 (2006) 89. M. Li, M. Xin, T. Miyashita, Polym. Int. 51 (2002) 889. S.L. Murov, I. Carmichel, G.L. Hug, Handbook of Photochemistry, Dekker, New York, 1993, p. 89.