INVESTIGADORES
PALMA Santiago Daniel
artículos
Título:
Potential use of Ascorbic Acid Based Surfactant as Skin Penetration Enhancers
Autor/es:
SANTIAGO DANIEL PALMA; MALETTO, B.; LO NOSTRO, PIERANDREA; HILARIO MANZO, RUBEN; PISTORESI, M. C.; ALBERTO ALLEMANDI, DANIEL
Revista:
Drug Development and Industrial Pharmacy
Referencias:
Año: 2006 vol. 32 p. 821 - 827
ISSN:
0363-9045
Resumen:
ABSTRACT 6-O-Ascorbic acid alkanoates (ASCn) are amphiphilic molecules
having physical-chemical properties that depend on the alkyl chain
length. The derivatives of low molecular weight (n < 11) have enough aqueous
solubility to produce self-assemblies at room temperature (¡Ö25¡ãC), while those
with longer alkyl chains possess a critical micellar temperature (CMT) higher
than 30¡ãC. At higher temperatures (T¡ã > CMT), ASCn aqueous suspensions
turn into either micellar solutions or gel phases, depending on the length of
the hydrophobic chain. On cooling, coagels are produced, which possess a
lamellar structure that exhibit sharp X-ray diffraction patterns and optical birefringence.
The semisolid consistency of such coagels is an interesting property
to formulate dermatological pharmaceutical dosage forms able to solubilize
and stabilize different drugs. The objective of the present study was the evaluation
of the enhancing permeation effect of ASCn with different chain lengths
and to correlate permeability changes with histological effects. With this purpose,
ASCn coagels containing anthralin (antipsoriasic drug) or fluorescein
isothiocyanate (FITC, hydrophobic fluorescent marker) were assayed on rat
skin (ex vivo) and mice skin (in vivo), respectively. Also, histological studies
were performed aimed at detecting some possible side effects of ASCn. No
inflammatory cellular response was observed in the skin when ASCn coagels
were applied, suggesting non-irritating properties. Light microscopy indicated
slight disruption and fragmentation of stratum corneum. The penetration of
ASCn through rat skin epidermis was very fast and quantitatively significant.
The permeation of anthralin was significantly increased when the drug was
vehiculized in ASCn coagels, compared to other pharmaceutical systems. The
results indicated that ASC12 seems to have the highest enhancing effect on
FITC permeation. ASC12 appears to be the compound that possesses the
highest capacity to enhance the penetration of the drugs. Furthermore, it has
the highest permeation of the serie.6-O-Ascorbic acid alkanoates (ASCn) are amphiphilic molecules
having physical-chemical properties that depend on the alkyl chain
length. The derivatives of low molecular weight (n < 11) have enough aqueous
solubility to produce self-assemblies at room temperature (¡Ö25¡ãC), while those
with longer alkyl chains possess a critical micellar temperature (CMT) higher
than 30¡ãC. At higher temperatures (T¡ã > CMT), ASCn aqueous suspensions
turn into either micellar solutions or gel phases, depending on the length of
the hydrophobic chain. On cooling, coagels are produced, which possess a
lamellar structure that exhibit sharp X-ray diffraction patterns and optical birefringence.
The semisolid consistency of such coagels is an interesting property
to formulate dermatological pharmaceutical dosage forms able to solubilize
and stabilize different drugs. The objective of the present study was the evaluation
of the enhancing permeation effect of ASCn with different chain lengths
and to correlate permeability changes with histological effects. With this purpose,
ASCn coagels containing anthralin (antipsoriasic drug) or fluorescein
isothiocyanate (FITC, hydrophobic fluorescent marker) were assayed on rat
skin (ex vivo) and mice skin (in vivo), respectively. Also, histological studies
were performed aimed at detecting some possible side effects of ASCn. No
inflammatory cellular response was observed in the skin when ASCn coagels
were applied, suggesting non-irritating properties. Light microscopy indicated
slight disruption and fragmentation of stratum corneum. The penetration of
ASCn through rat skin epidermis was very fast and quantitatively significant.
The permeation of anthralin was significantly increased when the drug was
vehiculized in ASCn coagels, compared to other pharmaceutical systems. The
results indicated that ASC12 seems to have the highest enhancing effect on
FITC permeation. ASC12 appears to be the compound that possesses the
highest capacity to enhance the penetration of the drugs. Furthermore, it has
the highest permeation of the serie.¡Ö25¡ãC), while those
with longer alkyl chains possess a critical micellar temperature (CMT) higher
than 30¡ãC. At higher temperatures (T¡ã > CMT), ASCn aqueous suspensions
turn into either micellar solutions or gel phases, depending on the length of
the hydrophobic chain. On cooling, coagels are produced, which possess a
lamellar structure that exhibit sharp X-ray diffraction patterns and optical birefringence.
The semisolid consistency of such coagels is an interesting property
to formulate dermatological pharmaceutical dosage forms able to solubilize
and stabilize different drugs. The objective of the present study was the evaluation
of the enhancing permeation effect of ASCn with different chain lengths
and to correlate permeability changes with histological effects. With this purpose,
ASCn coagels containing anthralin (antipsoriasic drug) or fluorescein
isothiocyanate (FITC, hydrophobic fluorescent marker) were assayed on rat
skin (ex vivo) and mice skin (in vivo), respectively. Also, histological studies
were performed aimed at detecting some possible side effects of ASCn. No
inflammatory cellular response was observed in the skin when ASCn coagels
were applied, suggesting non-irritating properties. Light microscopy indicated
slight disruption and fragmentation of stratum corneum. The penetration of
ASCn through rat skin epidermis was very fast and quantitatively significant.
The permeation of anthralin was significantly increased when the drug was
vehiculized in ASCn coagels, compared to other pharmaceutical systems. The
results indicated that ASC12 seems to have the highest enhancing effect on
FITC permeation. ASC12 appears to be the compound that possesses the
highest capacity to enhance the penetration of the drugs. Furthermore, it has
the highest permeation of the serie.¡ãC. At higher temperatures (T¡ã > CMT), ASCn aqueous suspensions
turn into either micellar solutions or gel phases, depending on the length of
the hydrophobic chain. On cooling, coagels are produced, which possess a
lamellar structure that exhibit sharp X-ray diffraction patterns and optical birefringence.
The semisolid consistency of such coagels is an interesting property
to formulate dermatological pharmaceutical dosage forms able to solubilize
and stabilize different drugs. The objective of the present study was the evaluation
of the enhancing permeation effect of ASCn with different chain lengths
and to correlate permeability changes with histological effects. With this purpose,
ASCn coagels containing anthralin (antipsoriasic drug) or fluorescein
isothiocyanate (FITC, hydrophobic fluorescent marker) were assayed on rat
skin (ex vivo) and mice skin (in vivo), respectively. Also, histological studies
were performed aimed at detecting some possible side effects of ASCn. No
inflammatory cellular response was observed in the skin when ASCn coagels
were applied, suggesting non-irritating properties. Light microscopy indicated
slight disruption and fragmentation of stratum corneum. The penetration of
ASCn through rat skin epidermis was very fast and quantitatively significant.
The permeation of anthralin was significantly increased when the drug was
vehiculized in ASCn coagels, compared to other pharmaceutical systems. The
results indicated that ASC12 seems to have the highest enhancing effect on
FITC permeation. ASC12 appears to be the compound that possesses the
highest capacity to enhance the penetration of the drugs. Furthermore, it has
the highest permeation of the serie.