Prolongation of Antidiuretic Response to Desmopressin Acetate by Iontophoretic Transdermal Delivery in Rats.

Nakakura, Masashi; Kato, Yasuki; Ito, Kunio

doi:10.1248/bpb.20.537

Cited by 4 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[30][31][32] In this respect, transdermal administration of desmopressin can therefore be a valuable alternative. Several studies evaluating transdermal delivery of desmopressin were recently conducted including microemulsion utilization, 16 iontophoresis, 33,34 and microneedle array technology 35 to overcome the skin barrier. Nevertheless, only the pharmacokinetic aspects of the desmopressin delivery were addressed in these experiments.…”

Section: Introductionmentioning

confidence: 99%

“…Desmopressin is usually administered in doses of 1−20 μg, perorally and intranasally, and by both routes it shows relatively low bioavailability of only 1% and 2−10%, respectively. − The very high hydrophilicity of desmopressin and its enzymatic degradation in the gastrointestinal tract seem to be the major reasons for the poor bioavailability of the drug. − In this respect, transdermal administration of desmopressin can therefore be a valuable alternative. Several studies evaluating transdermal delivery of desmopressin were recently conducted including microemulsion utilization, iontophoresis, , and microneedle array technology to overcome the skin barrier. Nevertheless, only the pharmacokinetic aspects of the desmopressin delivery were addressed in these experiments.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Concentration- and Temperature-Induced Effects of Incorporated Desmopressin on the Properties of Reverse Hexagonal Mesophase

et al. 2009

View full text Add to dashboard Cite

In this paper we report on the solubilization of desmopressin, as a model for peptide drugs, into reverse hexagonal (H(II)) liquid crystals. Concentration- and temperature-induced interactions of desmopressin, as well as the conformation of the peptide, were studied using small-angle X-ray scattering, ATR-FTIR spectroscopy, SD-NMR, and rheological measurements. A considerable increase (up to 6 A) in the lattice parameter of the mesophases was obtained upon incorporation of the peptide. According to the ATR-FTIR analysis, the chaotropic effect of peptide embedment was assigned to its interactions with hydroxyls of monoglyceride in the outer interface region. These interactions had only a minor influence on the conformation of the peptide; weakening or opening the gamma-turns resulted in partial binding of the peptide's free carbonyls to monoolein. Temperature-dependent SAXS measurements displayed a chaotropic destabilizing effect of desmopressin on the structure, shifting toward the lower temperature H(II)-L(2) structural transition. Temperature increase resulted in an increase of the domain size in the presence of the peptide, in contrast to the trend observed in the empty mesophase. SD-NMR analysis enabled distinguishing between two factors impeding the diffusion of the peptide: the restriction of motion due to the geometrical constrain of diffusion within the water tubes, and the interactions of the guest molecule with monoglyceride. The onset of the critical behavior at 45 degrees C was found to be significant, indicating considerable weakening of the monoglyceride and desmopressin interactions and the destabilizing effect of the peptide on the mesophase above this temperature. Similar temperature-dependent behavior was revealed by rheological measurements displaying the same onset of the critical behavior. It was demonstrated by Franz diffusion cell measurements that hexagonal mesophases can potentially be used as delivery vehicles for sustained delivery of desmopressin.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Concentration- and Temperature-Induced Effects of Incorporated Desmopressin on the Properties of Reverse Hexagonal Mesophase

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Permeation of the drug across the skin remained a challenging task for several drug candidates due to the crystalline physiological nature of stratum corneum (SC) as a critical barrier. Therefore, desmopressin acetate was well explored and reported for transdermal delivery using physical methods, such as iontophoresis in a rat model [ 11 , 12 , 44 , 45 ]. However, no reports have been published using vesicular-based transdermal delivery of desmopressin acetate for safe and efficient delivery.…”

Section: Resultsmentioning

confidence: 99%

“…Our formulation (ODEL1) extended release of 19.92 µg of desmopressin acetate over a period of 240 min (16 times higher prolongation). Thus, transdermal elastic liposome formulation controlled and sustained the release profile of the drug for minimum plasma fluctuation (inter-subject variability) and prolonged therapeutic effect [ 44 ]. This controlled release may be attributed to the lipid bilayer as the first-rate controlling factor, and SC layer as the main-rate controlling physiological factor.…”

Section: Resultsmentioning

confidence: 99%

Experimental Design Based Optimization and Ex Vivo Permeation of Desmopressin Acetate Loaded Elastic Liposomes Using Rat Skin

et al. 2021

View full text Add to dashboard Cite

The study aimed to develop elastic-liposome-based transdermal delivery of desmopressin acetate for enhanced permeation to control enuresis, central diabetes insipidus, and traumatic injury. Elastic liposomes (ELs)-loaded desmopressin acetate was prepared, optimized, and evaluated for improved transdermal permeation profiles using rat skin. Full factorial design with independent factors (X1 for lipid and X2 for surfactant) at three levels was used against four responses (Y1, Y2, Y3, and Y4) (dependent variables). Formulations were characterized for vesicle size, polydispersity index (PDI), zeta potential, % entrapment efficiency (% EE), in vitro drug release, in vitro hemolysis potential, ex vivo drug permeation and drug deposition (DD), and ex vivo vesicle–skin interaction using scanning electron microscopy studies. The optimized formulation ODEL1 based on desirability function was found to have vesicle size, % EE, % DR, and permeation flux values of 118.7 nm, 78.9%, 75.1%, and 5.3 µg/h·cm2, respectively, which were close to predicted values. In vitro release profiles indicated slow and sustained delivery. Permeation flux values of ODEL1 and ODEL2 were 5.3 and 3.1 µg/h·cm2, respectively, which are 7.5- and 4.4-fold higher as compared to DS (0.71 µg/h·cm2). The obtained flux was relatively higher than the clinical target value of the drug for therapeutic efficacy. Moreover, the DD value of ODEL1 was significantly higher than ODEL2 and DS. Hemocompatibility study confirmed safety concerns. Finally, vesicle–skin interaction corroborated mechanistic views of permeation through rat skin. Conclusively, the transdermal delivery may be a suitable alternative to oral and nasal delivery to treat nocturnal enuresis, central diabetes insipidus, hemophilia A and von Willebrand’s disease, and any traumatic injuries.

show abstract

Transdermal delivery of desmopressin using a coated microneedle array patch system

Cormier¹,

Johnson²,

Ameri³

et al. 2004

Journal of Controlled Release

150

132

View full text Add to dashboard Cite

Prolongation of Antidiuretic Response to Desmopressin Acetate by Iontophoretic Transdermal Delivery in Rats.

Cited by 4 publications

References 0 publications

Concentration- and Temperature-Induced Effects of Incorporated Desmopressin on the Properties of Reverse Hexagonal Mesophase

Concentration- and Temperature-Induced Effects of Incorporated Desmopressin on the Properties of Reverse Hexagonal Mesophase

Experimental Design Based Optimization and Ex Vivo Permeation of Desmopressin Acetate Loaded Elastic Liposomes Using Rat Skin

Transdermal delivery of desmopressin using a coated microneedle array patch system

Contact Info

Product

Resources

About