TY  - JOUR
AU  - Kovačević, Anđelka
AU  - Mueller, Rainer H.
AU  - Savić, Snežana
AU  - Vuleta, Gordana
AU  - Keck, Cornelia M.
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2189
AB  - Polyhydroxy surfactants are nonionic ethylene oxide free stabilizers known for their complimentary dermatological properties and favorable environmental profile. The aim of this study was to develop solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants varying in the chemical structure and to investigate the influence of the surfactants on the characteristics of the particles. Particles were produced by hot high pressure homogenization and the physico-chemical properties, e.g. contact angle, particle size, size distribution, zeta potential and crystallinity were determined. Results showed that the chemical structure of the surfactants influences the contact angle, particle size and crystallinity. Furthermore, the low surfactants concentration used (1% (w/w)) allowed the formation of the particles with a mean size below 200 nm, polydispersity index lower than 0.1 and sufficient physical stability for at least 6 months. As postulated by the zeta potential analysis stabilization ability of the surfactants was attributed to the superposition of electrostatic and steric effect which complement each other. All SLN formulations consisted of the same lipid matrix, but were found to possess different crystallinity indices. These differences are obviously created by the differences in the chemical structure of the surfactants. Therefore, the polyhydroxy surfactants investigated in this study can be judged to be novel suitable stabilizers for the formulation of well-skin tolerable SLN. The use of specific chemical structures of the surfactants can be used for the production of "tailor-made" SLN in the future.
PB  - Elsevier Science BV, Amsterdam
T2  - Colloids and Surfaces A: Physicochemical and Engineering Aspects
T1  - Solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants: Preparation, characterization and physical stability investigation
VL  - 444
SP  - 15
EP  - 25
DO  - 10.1016/j.colsurfa.2013.12.023
ER  - 

@article{
author = "Kovačević, Anđelka and Mueller, Rainer H. and Savić, Snežana and Vuleta, Gordana and Keck, Cornelia M.",
year = "2014",
abstract = "Polyhydroxy surfactants are nonionic ethylene oxide free stabilizers known for their complimentary dermatological properties and favorable environmental profile. The aim of this study was to develop solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants varying in the chemical structure and to investigate the influence of the surfactants on the characteristics of the particles. Particles were produced by hot high pressure homogenization and the physico-chemical properties, e.g. contact angle, particle size, size distribution, zeta potential and crystallinity were determined. Results showed that the chemical structure of the surfactants influences the contact angle, particle size and crystallinity. Furthermore, the low surfactants concentration used (1% (w/w)) allowed the formation of the particles with a mean size below 200 nm, polydispersity index lower than 0.1 and sufficient physical stability for at least 6 months. As postulated by the zeta potential analysis stabilization ability of the surfactants was attributed to the superposition of electrostatic and steric effect which complement each other. All SLN formulations consisted of the same lipid matrix, but were found to possess different crystallinity indices. These differences are obviously created by the differences in the chemical structure of the surfactants. Therefore, the polyhydroxy surfactants investigated in this study can be judged to be novel suitable stabilizers for the formulation of well-skin tolerable SLN. The use of specific chemical structures of the surfactants can be used for the production of "tailor-made" SLN in the future.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Colloids and Surfaces A: Physicochemical and Engineering Aspects",
title = "Solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants: Preparation, characterization and physical stability investigation",
volume = "444",
pages = "15-25",
doi = "10.1016/j.colsurfa.2013.12.023"
}

Kovačević, A., Mueller, R. H., Savić, S., Vuleta, G.,& Keck, C. M.. (2014). Solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants: Preparation, characterization and physical stability investigation. in Colloids and Surfaces A: Physicochemical and Engineering Aspects
Elsevier Science BV, Amsterdam., 444, 15-25.
https://doi.org/10.1016/j.colsurfa.2013.12.023

Kovačević A, Mueller RH, Savić S, Vuleta G, Keck CM. Solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants: Preparation, characterization and physical stability investigation. in Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2014;444:15-25.
doi:10.1016/j.colsurfa.2013.12.023 .

Kovačević, Anđelka, Mueller, Rainer H., Savić, Snežana, Vuleta, Gordana, Keck, Cornelia M., "Solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants: Preparation, characterization and physical stability investigation" in Colloids and Surfaces A: Physicochemical and Engineering Aspects, 444 (2014):15-25,
https://doi.org/10.1016/j.colsurfa.2013.12.023 . .

TY  - JOUR
AU  - Keck, Cornelia M.
AU  - Kovacević, Anđelka
AU  - Mueller, Rainer H.
AU  - Savić, Snežana
AU  - Vuleta, Gordana
AU  - Milić, Jela
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2078
AB  - Alkyl polyglycosides (APGs) represent a group of nonionic tensides with excellent skin compatibility. Thus they seem to be excellent stabilizers for lipid nanoparticles for dermal application. To investigate this, different APGs were selected to evaluate their influence on the formation and characteristics of solid lipid nanoparticles (SLN). Contact angle analysis of the aqueous solutions/dispersions of the APGs on cetyl palmitate films revealed good wettability for all APG surfactants. Cetyl palmitate based SLN were prepared by hot high pressure homogenization and subjected to particle size, charge and inner structure analysis. 1% of each APG was sufficient to obtain SLN with a mean size between 150 nm and 175 nm and a narrow size distribution. The zeta potential in water was similar to -50 mV; the values in the original medium were distinctly lower, but still sufficient high to provide good physical stability. Physical stability at different temperatures (5 degrees C, 25 degrees C and 40 degrees C) was confirmed by a constant particle size over an observation period of 90 days in all dispersions. In comparison to SLN stabilized with classical surfactants, e.g., Polysorbate, APG stabilized SLN possess a smaller size, improved physical stability and contain less surfactant. Therefore, the use of APGs for the stabilization of lipid nanoparticles is superior in comparison to classical stabilizers. Further, the results indicate that the length of the alkyl chain of the APG influences the diminution efficacy, the final particle size and the crystallinity of the particles. APGs with short alkyl chain led to a faster reduction in size during high pressure homogenization, to a smaller particle size of the SLN and to a lower recrystallization index, i.e., to a lower crystallinity of the SLN. The crystallinity of the SLN increased with an increase in the alkyl chain length of APGs. Therefore, by using the tested APGs differing in the alkyl chain length, not only small sized and physically stable but also SLN with different sizes and crystallinity can be obtained. An optimized selection of these stabilizers might therefore enable the production of lipid nanoparticles with "tailor-made" properties.
PB  - Elsevier Science BV, Amsterdam
T2  - International Journal of Pharmaceutics
T1  - Formulation of solid lipid nanoparticles (SLN): The value of different alkyl polyglucoside surfactants
VL  - 474
IS  - 1-2
SP  - 33
EP  - 41
DO  - 10.1016/j.ijpharm.2014.08.008
ER  - 

@article{
author = "Keck, Cornelia M. and Kovacević, Anđelka and Mueller, Rainer H. and Savić, Snežana and Vuleta, Gordana and Milić, Jela",
year = "2014",
abstract = "Alkyl polyglycosides (APGs) represent a group of nonionic tensides with excellent skin compatibility. Thus they seem to be excellent stabilizers for lipid nanoparticles for dermal application. To investigate this, different APGs were selected to evaluate their influence on the formation and characteristics of solid lipid nanoparticles (SLN). Contact angle analysis of the aqueous solutions/dispersions of the APGs on cetyl palmitate films revealed good wettability for all APG surfactants. Cetyl palmitate based SLN were prepared by hot high pressure homogenization and subjected to particle size, charge and inner structure analysis. 1% of each APG was sufficient to obtain SLN with a mean size between 150 nm and 175 nm and a narrow size distribution. The zeta potential in water was similar to -50 mV; the values in the original medium were distinctly lower, but still sufficient high to provide good physical stability. Physical stability at different temperatures (5 degrees C, 25 degrees C and 40 degrees C) was confirmed by a constant particle size over an observation period of 90 days in all dispersions. In comparison to SLN stabilized with classical surfactants, e.g., Polysorbate, APG stabilized SLN possess a smaller size, improved physical stability and contain less surfactant. Therefore, the use of APGs for the stabilization of lipid nanoparticles is superior in comparison to classical stabilizers. Further, the results indicate that the length of the alkyl chain of the APG influences the diminution efficacy, the final particle size and the crystallinity of the particles. APGs with short alkyl chain led to a faster reduction in size during high pressure homogenization, to a smaller particle size of the SLN and to a lower recrystallization index, i.e., to a lower crystallinity of the SLN. The crystallinity of the SLN increased with an increase in the alkyl chain length of APGs. Therefore, by using the tested APGs differing in the alkyl chain length, not only small sized and physically stable but also SLN with different sizes and crystallinity can be obtained. An optimized selection of these stabilizers might therefore enable the production of lipid nanoparticles with "tailor-made" properties.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Journal of Pharmaceutics",
title = "Formulation of solid lipid nanoparticles (SLN): The value of different alkyl polyglucoside surfactants",
volume = "474",
number = "1-2",
pages = "33-41",
doi = "10.1016/j.ijpharm.2014.08.008"
}

Keck, C. M., Kovacević, A., Mueller, R. H., Savić, S., Vuleta, G.,& Milić, J.. (2014). Formulation of solid lipid nanoparticles (SLN): The value of different alkyl polyglucoside surfactants. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 474(1-2), 33-41.
https://doi.org/10.1016/j.ijpharm.2014.08.008

Keck CM, Kovacević A, Mueller RH, Savić S, Vuleta G, Milić J. Formulation of solid lipid nanoparticles (SLN): The value of different alkyl polyglucoside surfactants. in International Journal of Pharmaceutics. 2014;474(1-2):33-41.
doi:10.1016/j.ijpharm.2014.08.008 .

Keck, Cornelia M., Kovacević, Anđelka, Mueller, Rainer H., Savić, Snežana, Vuleta, Gordana, Milić, Jela, "Formulation of solid lipid nanoparticles (SLN): The value of different alkyl polyglucoside surfactants" in International Journal of Pharmaceutics, 474, no. 1-2 (2014):33-41,
https://doi.org/10.1016/j.ijpharm.2014.08.008 . .

TY  - JOUR
AU  - Kovacević, Anđelka
AU  - Savić, Snežana
AU  - Vuleta, Gordana
AU  - Mueller, Rainer H.
AU  - Keck, Cornelia M.
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1548
AB  - The two polyhydroxy surfactants polyglycerol 6-distearate (Plurol (R) Stearique WL1009 - (PS)) and caprylyl/capryl glucoside (Plantacare (R) 810 - (PL)) are a class of PEG-free stabilizers, made from renewable resources. They were investigated for stabilization of aqueous solid lipid nanoparticle (SIN) and nanostructured lipid carrier (NLC) dispersions. Production was performed by high pressure homogenization, analysis by photon correlation spectroscopy (PCS), laser diffraction (LD), zeta potential measurements and differential scanning calorimetry (DSC). Particles were made from Cutina CP as solid lipid only (SIN) and its blends with Miglyol 812 (NLC, the blends containing increasing amounts of oil from 20% to 60%). The obtained particle sizes were identical for both surfactants, about 200 nm with polydispersity indices below 0.20 (PCS), and unimodal size distribution (ID). All dispersions with both surfactants were physically stable for 3 months at room temperature, but Plantacare (PL) showing a superior stability. The melting behaviour and crystallinity of bulk lipids/lipid blends were compared to the nanoparticles. Both were lower for the nanoparticles. The crystallinity of dispersions stabilized with PS was higher, the zeta potential decreased with storage time associated with this higher crystallinity, and leading to a few, but negligible larger particles. The lower crystallinity particles stabilized with PL remained unchanged in zeta potential (about -50 mV) and in size. These data show that surfactants have a distinct influence on the particle matrix struture (and related stability and drug loading), to which too little attention was given by now. Despite being from the same surfactant class, the differences on the structure are pronounced. They are attributed to the hydrophobic-lipophilic tail structure with one-point anchoring in the interface (PL), and the loop conformation of PS with two hydrophobic anchor points, i.e. their molecular structure and its interaction with the matrix surface and matrix bulk. Analysis of the effects of the surfactants on the particle matrix structure could potentially be used to further optimization of stability, drug loading and may be drug release.
PB  - Elsevier Science BV, Amsterdam
T2  - International Journal of Pharmaceutics
T1  - Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): Effects on size, physical stability and particle matrix structure
VL  - 406
IS  - 1-2
SP  - 163
EP  - 172
DO  - 10.1016/j.ijpharm.2010.12.036
ER  - 

@article{
author = "Kovacević, Anđelka and Savić, Snežana and Vuleta, Gordana and Mueller, Rainer H. and Keck, Cornelia M.",
year = "2011",
abstract = "The two polyhydroxy surfactants polyglycerol 6-distearate (Plurol (R) Stearique WL1009 - (PS)) and caprylyl/capryl glucoside (Plantacare (R) 810 - (PL)) are a class of PEG-free stabilizers, made from renewable resources. They were investigated for stabilization of aqueous solid lipid nanoparticle (SIN) and nanostructured lipid carrier (NLC) dispersions. Production was performed by high pressure homogenization, analysis by photon correlation spectroscopy (PCS), laser diffraction (LD), zeta potential measurements and differential scanning calorimetry (DSC). Particles were made from Cutina CP as solid lipid only (SIN) and its blends with Miglyol 812 (NLC, the blends containing increasing amounts of oil from 20% to 60%). The obtained particle sizes were identical for both surfactants, about 200 nm with polydispersity indices below 0.20 (PCS), and unimodal size distribution (ID). All dispersions with both surfactants were physically stable for 3 months at room temperature, but Plantacare (PL) showing a superior stability. The melting behaviour and crystallinity of bulk lipids/lipid blends were compared to the nanoparticles. Both were lower for the nanoparticles. The crystallinity of dispersions stabilized with PS was higher, the zeta potential decreased with storage time associated with this higher crystallinity, and leading to a few, but negligible larger particles. The lower crystallinity particles stabilized with PL remained unchanged in zeta potential (about -50 mV) and in size. These data show that surfactants have a distinct influence on the particle matrix struture (and related stability and drug loading), to which too little attention was given by now. Despite being from the same surfactant class, the differences on the structure are pronounced. They are attributed to the hydrophobic-lipophilic tail structure with one-point anchoring in the interface (PL), and the loop conformation of PS with two hydrophobic anchor points, i.e. their molecular structure and its interaction with the matrix surface and matrix bulk. Analysis of the effects of the surfactants on the particle matrix structure could potentially be used to further optimization of stability, drug loading and may be drug release.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Journal of Pharmaceutics",
title = "Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): Effects on size, physical stability and particle matrix structure",
volume = "406",
number = "1-2",
pages = "163-172",
doi = "10.1016/j.ijpharm.2010.12.036"
}

Kovacević, A., Savić, S., Vuleta, G., Mueller, R. H.,& Keck, C. M.. (2011). Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): Effects on size, physical stability and particle matrix structure. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 406(1-2), 163-172.
https://doi.org/10.1016/j.ijpharm.2010.12.036

Kovacević A, Savić S, Vuleta G, Mueller RH, Keck CM. Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): Effects on size, physical stability and particle matrix structure. in International Journal of Pharmaceutics. 2011;406(1-2):163-172.
doi:10.1016/j.ijpharm.2010.12.036 .

Kovacević, Anđelka, Savić, Snežana, Vuleta, Gordana, Mueller, Rainer H., Keck, Cornelia M., "Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): Effects on size, physical stability and particle matrix structure" in International Journal of Pharmaceutics, 406, no. 1-2 (2011):163-172,
https://doi.org/10.1016/j.ijpharm.2010.12.036 . .