rus
Issue #1/2025
E.I.Diskaeva, O.V.Vecher, I.A.Bazikov, E.N.Diskaeva, K.S.Elbekyan, E.S.Lopatina
EVALUATION OF THE TEMPERATURE INFLUENCE EFFECT ON STABILITY AND PARTICLE SIZE OF NIOSOMAL DISPERSIONS BASED ON PEG-12 DIMETHICONE
EVALUATION OF THE TEMPERATURE INFLUENCE EFFECT ON STABILITY AND PARTICLE SIZE OF NIOSOMAL DISPERSIONS BASED ON PEG-12 DIMETHICONE
DOI: https://doi.org/10.22184/1993-8578.2025.18.1.8.15
In this paper, the dynamics of changes in the ζ potential and particle sizes of niosomal dispersions of various concentrations under temperature variation is studied by the method of dynamic light scattering. The average diameter changes of the niosomes and the polydispersity index were revealed. The most significant influence of temperature on the considered parameters was observed in the interval 303–313 K. The experimental data indicated an increase in the zeta potential with increasing temperature. Based on the analysis performed, possibility of increasing the niosomal dispersions stability by means of temperature influence was confirmed.
In this paper, the dynamics of changes in the ζ potential and particle sizes of niosomal dispersions of various concentrations under temperature variation is studied by the method of dynamic light scattering. The average diameter changes of the niosomes and the polydispersity index were revealed. The most significant influence of temperature on the considered parameters was observed in the interval 303–313 K. The experimental data indicated an increase in the zeta potential with increasing temperature. Based on the analysis performed, possibility of increasing the niosomal dispersions stability by means of temperature influence was confirmed.
Теги: organosilicon niosomes polydispersity index stability zeta potential дзета-потенциал индекс полидисперсности кремнийорганические ниосомы стабильность
INTRODUCTION
Targeted delivery of controlled-release rate drugs has received tremendous attention in recent years. Application of nanotechnology in medicine has led to development of multifunctional nanoparticles that can be filled with different drugs. Nanocontainers represent an excellent approach to drug delivery with promising functions such as protection of drugs from degradation and cleavage, and controlled release. The most widely used among them are both liposomes and their various combinations and niosomes [1–4].
Niosomes are vesicles, typically in the nanometre range, consisting of a closed bilayer structure represented by non-ionogenic surfactants in an aqueous system.
Niosomes are very promising carriers to deliver the numerous pharmacological and diagnostic agents. Due to their non-ionic nature, they have excellent biocompatibility and low toxicity. The unique structure of niosomes allows to develop new efficient drug delivery systems with possibility of loading both hydrophilic and lipophilic drugs. Hydrophilic and lipophilic drugs are retained in the aqueous core and membrane bilayer of the niosome respectively.
Many studies have been devoted to finding the appropriate composition of components in the synthesis of niosomes to ensure optimal physicochemical properties [5–8].
Organosilicon niosomes are composed of PEG-12 Dimethicone, which has amphiphilic properties allowing orientation in dispersion with the water-soluble part (polyethylene glycol) to water and the fat-soluble part (dimethicone) to lipids. A thin elastic shell allows them to move through the intercellular spaces that constitute the lipid matrix.
The advantages that can be obtained by using siloxane surfactants for vesicle formation and drug loading are supported by the facts that, firstly, presence of a covalent Si–O bond in the hydrophobic part of the polydimethylsiloxane emulsifier backbone molecule, which has great elasticity and reactivity, allows targeting delivery of a wide range of SAS and their targeted release from the vesicle [9]. Secondly, siloxane surfactants "spontaneously" form vesicles upon contact with water, and therefore they eliminate the use of energy-intensive processes such as ultrasonic treatment that are required for non-siloxane-based surfactants [10].
However, niosomal dispersions, as well as any other colloidal systems, are thermodynamically unstable; therefore, assessment of their stability is of undoubted practical importance at the stages of development, production and storage of niosomal preparations. Determination of physicochemical characteristics of niosomes is also important for clinical application.
One of the main parameters determining stability of disperse systems and being an indicator of the surface charge of particles and a measure of electrostatic interaction between particles is the ζ potential. This parameter also allows predicting interaction of niosomes with cells.
Another important factor in transdermal drug delivery is particle size. Thus, the smaller the diameter of niosomes, the higher their penetration efficiency into deep skin layers and lesions. Size factors have a significant impact on many physicochemical characteristics of nanocontainers, so determining the size and dispersibility of niosomal dispersions at preparation stage will not only optimise the manufacturing modes, but will also make it possible to predict the final characteristics of the resulting drugs.
The aim of the presented work was to study the effect of temperature change on stability and particle sizes of niosomal dispersions of different concentrations, as well as to analyse possible ways to improve their stability.
RESEARCH METHODS
Organosilicon niosomes consisting of a double layer of non-ionogenic emulsifier dimethicone copolyols, which are esters of polyethylene glycol and polydimethylsiloxane backbone, were chosen as the object of study [11].
Niosomes were prepared at room temperature by vigorous mechanical shaking on a shaker for 5 minutes of PEG-12 Dimethicone emulsion followed by ultrasonic treatment. Sounding mode: frequency 20 kHz, power 200 W, exposure: 10–15 minutes. Then, emulsification was carried out on an APV homogeniser (APV Lab Series Homogenizers-1000) to stabilise hydrogen ion concentration (pH) to 6.6–7.0 and to form a homogeneous structure. Bidistilled water was used to dilute niosomal dispersions to specified concentrations.
Zeta potential measurements were performed using a Photocor Compact-Z system (Russia) at an angle of 20°, laser wavelength 636.6 nm, power 25 mW. The data of zeta potential measurements were presented as the mean value ±SD (mV).
To study the effect of temperature on the zeta potential value of niosomal dispersions, the studied samples were heated on a water bath (UT – 4304E) in the temperature range of 303–333 K.
The dynamic light scattering (DLS) method was used to determine the size of niosomes. This method involves calculation of the hydrodynamic diameter dh of spheres that would move in the liquid with the same velocity as the particles under study. The dh measurements were carried out using the Photocor Compact-Z system (Russia) to estimate correlation function of fluctuations in intensity fluctuations of laser radiation with a wavelength of 636.6 nm scattered on niosomes at an angle of 20°. The width of particle size distribution was characterised by the polydispersity index (PDI).
The polydispersity index was calculated according to the formula:
(1)
where dh is the hydrodynamic diameter of niosomes, nm; σ is the mean square deviation of the hydrodynamic diameter, nm.
Low values of the polydispersity index indicate a narrow particle size distribution, i.e., reflecting homogeneity of dispersion, while a high PDI suggests a broad size distribution, i.e., a greater degree of heterogeneity [12].
RESULTS AND DISCUSSION
It is known that surface charge of niosomes plays an important role in their behaviour. In general, charged niosomes are more resistant to aggregation than uncharged vesicles [13]. High surface charges enable niosomes to suspend well in water, which may be useful for their storage and administration. The effect of concentration on zeta potential can provide additional information for product formulation to maximise stability [14].
The zeta potential value of PEG-12 Dimethicone based niosomal dispersions was determined five times and then the mean value was calculated. The values of ζ potential of niosomal dispersions of studied concentrations measured directly after dilution at room temperature are given in Table 1.
Since the niosomal dispersions with concentrations of 0.005% and 1.0% inherently have a low zeta potential, i.e., they are unstable, they were eliminated from the experiment.
In order to evaluate the effect of temperature on stability of niosomal dispersions, the remaining samples were subjected to heating in the temperature range of 303–333 K. The obtained results are presented in Table 2.
Graphical dependences of the zeta potential value of niosomal dispersions of different concentrations on temperature are presented in Fig.1.
The analysis of graphical dependences shows an increase in the absolute value of zeta-potential for all studied samples of niosomal dispersions, which is probably related to increase intensity of thermal motion of counterions and growing the electric double layer thickness. The greatest growth is observed for more dilute niosomal dispersion.
When the temperature increases in the range 303–313 K, a significant increase in zeta potential is observed, which may be associated with a sharp transition of part of counterions from adsorption layer to the diffuse layer. Further increase of temperature favours increasing of competition of diffusion of counterions with desorption of potential-determining ions, which leads already to insignificant growth of zeta-potential value.
The results also indicate that the zeta potential at low concentrations exhibits a more pronounced temperature dependence. In addition, the results demonstrate that the zeta potential value decreases with increasing solution concentration. This is in agreement with the results of other studies [15, 16]. It can be noted that the zeta potentials of systems with lower concentration are less affected by temperature change than their counterparts with higher concentration.
The results of determining the mean particle size value of niosomal dispersions and the values of polydispersity indices are presented in Table 3.
Changes in the values of the mean hydrodynamic diameter of niosomes with increasing temperature are nonmonotonic. The largest changes are observed in the temperature range 303–313 K. The values of the polydispersity index tend to decrease with increasing temperature, which may indicate some growth of system homogeneity.
Thus, varying temperature allows to obtain more stable forms of niosomes of given concentrations having a more homogeneous structure.
CONCLUSIONS
The sizes of niosomal dispersion particles and the values of ζ potentials were determined by the dynamic light scattering method. In all cases the zeta-potential is a negative value. The dependence of zeta-potential on temperature and concentration of dispersed phase particles of niosomal dispersions has been studied. It is proved that the structural properties and characteristics of niosomes can be improved by varying temperature. The obtained results can be useful both at the stage of preparing of niosomal forms of drugs and in the process of their storage and administration.
PEER REVIEW INFO
Editorial board thanks the anonymous reviewer(s) for their contribution to the peer review of this work. It is also grateful for their consent to publish papers on the journal’s website and SEL eLibrary eLIBRARY.RU.
Declaration of Competing Interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Targeted delivery of controlled-release rate drugs has received tremendous attention in recent years. Application of nanotechnology in medicine has led to development of multifunctional nanoparticles that can be filled with different drugs. Nanocontainers represent an excellent approach to drug delivery with promising functions such as protection of drugs from degradation and cleavage, and controlled release. The most widely used among them are both liposomes and their various combinations and niosomes [1–4].
Niosomes are vesicles, typically in the nanometre range, consisting of a closed bilayer structure represented by non-ionogenic surfactants in an aqueous system.
Niosomes are very promising carriers to deliver the numerous pharmacological and diagnostic agents. Due to their non-ionic nature, they have excellent biocompatibility and low toxicity. The unique structure of niosomes allows to develop new efficient drug delivery systems with possibility of loading both hydrophilic and lipophilic drugs. Hydrophilic and lipophilic drugs are retained in the aqueous core and membrane bilayer of the niosome respectively.
Many studies have been devoted to finding the appropriate composition of components in the synthesis of niosomes to ensure optimal physicochemical properties [5–8].
Organosilicon niosomes are composed of PEG-12 Dimethicone, which has amphiphilic properties allowing orientation in dispersion with the water-soluble part (polyethylene glycol) to water and the fat-soluble part (dimethicone) to lipids. A thin elastic shell allows them to move through the intercellular spaces that constitute the lipid matrix.
The advantages that can be obtained by using siloxane surfactants for vesicle formation and drug loading are supported by the facts that, firstly, presence of a covalent Si–O bond in the hydrophobic part of the polydimethylsiloxane emulsifier backbone molecule, which has great elasticity and reactivity, allows targeting delivery of a wide range of SAS and their targeted release from the vesicle [9]. Secondly, siloxane surfactants "spontaneously" form vesicles upon contact with water, and therefore they eliminate the use of energy-intensive processes such as ultrasonic treatment that are required for non-siloxane-based surfactants [10].
However, niosomal dispersions, as well as any other colloidal systems, are thermodynamically unstable; therefore, assessment of their stability is of undoubted practical importance at the stages of development, production and storage of niosomal preparations. Determination of physicochemical characteristics of niosomes is also important for clinical application.
One of the main parameters determining stability of disperse systems and being an indicator of the surface charge of particles and a measure of electrostatic interaction between particles is the ζ potential. This parameter also allows predicting interaction of niosomes with cells.
Another important factor in transdermal drug delivery is particle size. Thus, the smaller the diameter of niosomes, the higher their penetration efficiency into deep skin layers and lesions. Size factors have a significant impact on many physicochemical characteristics of nanocontainers, so determining the size and dispersibility of niosomal dispersions at preparation stage will not only optimise the manufacturing modes, but will also make it possible to predict the final characteristics of the resulting drugs.
The aim of the presented work was to study the effect of temperature change on stability and particle sizes of niosomal dispersions of different concentrations, as well as to analyse possible ways to improve their stability.
RESEARCH METHODS
Organosilicon niosomes consisting of a double layer of non-ionogenic emulsifier dimethicone copolyols, which are esters of polyethylene glycol and polydimethylsiloxane backbone, were chosen as the object of study [11].
Niosomes were prepared at room temperature by vigorous mechanical shaking on a shaker for 5 minutes of PEG-12 Dimethicone emulsion followed by ultrasonic treatment. Sounding mode: frequency 20 kHz, power 200 W, exposure: 10–15 minutes. Then, emulsification was carried out on an APV homogeniser (APV Lab Series Homogenizers-1000) to stabilise hydrogen ion concentration (pH) to 6.6–7.0 and to form a homogeneous structure. Bidistilled water was used to dilute niosomal dispersions to specified concentrations.
Zeta potential measurements were performed using a Photocor Compact-Z system (Russia) at an angle of 20°, laser wavelength 636.6 nm, power 25 mW. The data of zeta potential measurements were presented as the mean value ±SD (mV).
To study the effect of temperature on the zeta potential value of niosomal dispersions, the studied samples were heated on a water bath (UT – 4304E) in the temperature range of 303–333 K.
The dynamic light scattering (DLS) method was used to determine the size of niosomes. This method involves calculation of the hydrodynamic diameter dh of spheres that would move in the liquid with the same velocity as the particles under study. The dh measurements were carried out using the Photocor Compact-Z system (Russia) to estimate correlation function of fluctuations in intensity fluctuations of laser radiation with a wavelength of 636.6 nm scattered on niosomes at an angle of 20°. The width of particle size distribution was characterised by the polydispersity index (PDI).
The polydispersity index was calculated according to the formula:
(1)
where dh is the hydrodynamic diameter of niosomes, nm; σ is the mean square deviation of the hydrodynamic diameter, nm.
Low values of the polydispersity index indicate a narrow particle size distribution, i.e., reflecting homogeneity of dispersion, while a high PDI suggests a broad size distribution, i.e., a greater degree of heterogeneity [12].
RESULTS AND DISCUSSION
It is known that surface charge of niosomes plays an important role in their behaviour. In general, charged niosomes are more resistant to aggregation than uncharged vesicles [13]. High surface charges enable niosomes to suspend well in water, which may be useful for their storage and administration. The effect of concentration on zeta potential can provide additional information for product formulation to maximise stability [14].
The zeta potential value of PEG-12 Dimethicone based niosomal dispersions was determined five times and then the mean value was calculated. The values of ζ potential of niosomal dispersions of studied concentrations measured directly after dilution at room temperature are given in Table 1.
Since the niosomal dispersions with concentrations of 0.005% and 1.0% inherently have a low zeta potential, i.e., they are unstable, they were eliminated from the experiment.
In order to evaluate the effect of temperature on stability of niosomal dispersions, the remaining samples were subjected to heating in the temperature range of 303–333 K. The obtained results are presented in Table 2.
Graphical dependences of the zeta potential value of niosomal dispersions of different concentrations on temperature are presented in Fig.1.
The analysis of graphical dependences shows an increase in the absolute value of zeta-potential for all studied samples of niosomal dispersions, which is probably related to increase intensity of thermal motion of counterions and growing the electric double layer thickness. The greatest growth is observed for more dilute niosomal dispersion.
When the temperature increases in the range 303–313 K, a significant increase in zeta potential is observed, which may be associated with a sharp transition of part of counterions from adsorption layer to the diffuse layer. Further increase of temperature favours increasing of competition of diffusion of counterions with desorption of potential-determining ions, which leads already to insignificant growth of zeta-potential value.
The results also indicate that the zeta potential at low concentrations exhibits a more pronounced temperature dependence. In addition, the results demonstrate that the zeta potential value decreases with increasing solution concentration. This is in agreement with the results of other studies [15, 16]. It can be noted that the zeta potentials of systems with lower concentration are less affected by temperature change than their counterparts with higher concentration.
The results of determining the mean particle size value of niosomal dispersions and the values of polydispersity indices are presented in Table 3.
Changes in the values of the mean hydrodynamic diameter of niosomes with increasing temperature are nonmonotonic. The largest changes are observed in the temperature range 303–313 K. The values of the polydispersity index tend to decrease with increasing temperature, which may indicate some growth of system homogeneity.
Thus, varying temperature allows to obtain more stable forms of niosomes of given concentrations having a more homogeneous structure.
CONCLUSIONS
The sizes of niosomal dispersion particles and the values of ζ potentials were determined by the dynamic light scattering method. In all cases the zeta-potential is a negative value. The dependence of zeta-potential on temperature and concentration of dispersed phase particles of niosomal dispersions has been studied. It is proved that the structural properties and characteristics of niosomes can be improved by varying temperature. The obtained results can be useful both at the stage of preparing of niosomal forms of drugs and in the process of their storage and administration.
PEER REVIEW INFO
Editorial board thanks the anonymous reviewer(s) for their contribution to the peer review of this work. It is also grateful for their consent to publish papers on the journal’s website and SEL eLibrary eLIBRARY.RU.
Declaration of Competing Interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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