Capsaicin and Piperine as Functional Excipients for Improved Drug Delivery across Nasal Epithelial Models

Gerber, Werner; Steyn, Dewald; Kotzé, A.F; Svitina, Hanna; Weldon, Ché; Hamman, Josias H.

doi:10.1055/a-0978-5172

Cited by 13 publications

(9 citation statements)

References 37 publications

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“…Sheep nasal mucosa represents similar histological and morphological structures to human nasal mucosa and can thus be used for permeation studies [ 31 , 32 , 33 , 34 ]. Ex vivo permeation studies were conducted across excised sheep nasal tissues mounted onto vertical Franz diffusion cells to determine the transmucosal delivery of F3 and F4, and compared to a simple solution of clozapine.…”

Section: Resultsmentioning

confidence: 99%

Clozapine-Encapsulated Binary Mixed Micelles in Thermosensitive Sol–Gels for Intranasal Administration

Tan

Pandey

Falconer

et al. 2022

Gels

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(1) Background: Clozapine is the most effective antipsychotic. It is, however, associated with many adverse drug reactions. Nose-to-brain (N2B) delivery offers a promising approach. This study aims to develop clozapine-encapsulated thermosensitive sol–gels for N2B delivery. (2) Methods: Poloxamer 407 and hydroxypropyl methylcellulose were mixed and hydrated with water. Glycerin and carbopol solutions were added to the mixture and stirred overnight at 2–8 °C. Clozapine 0.1% w/w was stirred with polysorbate 20 (PS20) or polysorbate 80 (PS80) at RT (25 °C) before being added to the polymer solution. The final formulation was made to 10 g with water, stirred overnight at 2–8 °C and then adjusted to pH 5.5. (3) Results: Formulations F3 (3% PS20) and F4 (3% PS80) were selected for further evaluation, as their gelation temperatures were near 28 °C. The hydrodynamic particle diameter of clozapine was 18.7 ± 0.2 nm in F3 and 20.0 ± 0.4 nm in F4. The results show a crystallinity change in clozapine to amorphous. Drug release studies showed a 59.1 ± 3.0% (F3) and 53.1 ± 2.7% (F4) clozapine release after 72 h. Clozapine permeated after 8 h was 20.8 ± 3.0% (F3) and 17.8 ± 3.1% (F4). The drug deposition was higher with F4 (144.8 ± 1.4 µg/g) than F3 (110.7 ± 2.7 µg/g). Both sol–gels showed no phase separation after 3 months. (4) Conclusions: Binary PS80-P407 mixed micelles were more thermodynamically stable and rigid due to the higher synergism of both surfactants. However, binary mixed PS20-P407 micelles showed better drug permeation across the nasal mucosa tissue and may be a preferable carrier system for the intranasal administration of clozapine.

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Section: Resultsmentioning

confidence: 99%

Clozapine-Encapsulated Binary Mixed Micelles in Thermosensitive Sol–Gels for Intranasal Administration

Tan

Pandey

Falconer

et al. 2022

Gels

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“…The lowest and highest percentage difference in apparent permeability between microparticulate formulations were 10.12% (without piperine) and 29.57% (with piperine), respectively. Previously published studies indicated that piperine enhances polarized paracellular transport by opening tight junctions [ 52 , 53 , 54 ].…”

Section: Resultsmentioning

confidence: 99%

Formulation of Chitosan Microparticles for Enhanced Intranasal Macromolecular Compound Delivery: Factors That Influence Particle Size during Ionic Gelation

Weyers

Peterson

Hamman

et al. 2022

Gels

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Therapeutic macromolecules (e.g., protein and peptide drugs) present bioavailability challenges via extravascular administration. The nasal route presents an alternative non-invasive route for these drugs, although low bioavailability remains challenging. Co-administration of permeation enhancers is a promising formulation approach to improve the delivery of poorly bioavailable drugs. The aim of this study was to prepare and characterize chitosan microparticulate formulations containing a macromolecular model compound (fluorescein isothiocyanate dextran 4400, FD-4) and a bioenhancer (piperine). Ionic gelation was used to produce chitosan microparticle delivery systems with two distinct microparticle sizes, differing one order of magnitude in size (±20 µm and ±200 µm). These two microparticle delivery systems were formulated into thermosensitive gels and their drug delivery performance was evaluated across ovine nasal epithelial tissues. Dissolution studies revealed a biphasic release pattern. Rheometry results demonstrated a sol-to-gel transition of the thermosensitive gel formulation at a temperature of 34 °C. The microparticles incorporating piperine showed a 1.2-fold increase in FD-4 delivery across the excised ovine nasal epithelial tissues as compared to microparticles without piperine. This study therefore contributed to advancements in ionic gelation methods for the formulation of particulate systems to enhance macromolecular nasal drug delivery.

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“…This nasal mucosa model was previously proven to mimic the properties of human excised nasal tissue [ 47 ]. Indeed, TEER values, which measure tissue integrity and tightness, were demonstrated to be similar to that of the human nasal mucosa ex vivo (75–180 Ω.cm²) [ 48 – 51 ].…”

Section: Discussionmentioning

confidence: 99%

Pre-referral intranasal artesunate powder for cerebral malaria: a proof-of-concept study

Kouakou

Millet

Fromentin

et al. 2022

Malar J

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Background Malaria still kills young children in rural endemic areas because early treatment is not available. Thus, the World Health Organization recommends the administration of artesunate suppositories as pre-referral treatment before transportation to the hospital in case of severe symptoms with an unavailable parenteral and oral treatment. However, negative cultural perception of the rectal route, and limited access to artesunate suppositories, could limit the use of artesunate suppositories. There is, therefore, a need for an alternative route for malaria pre-referral treatment. The aim of this study was to assess the potential of intranasal route for malaria pre-referral treatment. Methods The permeability of artesunate through human nasal mucosa was tested in vitro. The Transepithelial Electrical Resistance (TEER) of the nasal mucosa was followed during the permeation tests. Beside, regional deposition of artesunate powder was assessed with an unidose drug delivery device in each nostril of a nasal cast. Artesunate quantification was performed using Liquid Chromatography coupled to tandem Mass Spectrometry. Results The experimental model of human nasal mucosa was successfully implemented. Using this model, artesunate powder showed a much better passage rate through human nasal mucosa than solution (26.8 ± 6.6% versus 2.1 ± 0.3%). More than half (62.3%) of the artesunate dose sprayed in the nostrils of the nasal cast was recovered in the olfactory areas (44.7 ± 8.6%) and turbinates (17.6 ± 3.3%) allowing nose-to-brain and systemic drug diffusion, respectively. Conclusion Artesunate powder showed a good permeation efficiency on human nasal mucosa. Moreover it can be efficiently sprayed in the nostrils using unidose device to reach the olfactory area leading to a fast nose-to-brain delivery as well as a systemic effect. Taken together, those results are part of the proof-of-concept for the use of intranasal artesunate as a malaria pre-referral treatment.

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Capsaicin and Piperine as Functional Excipients for Improved Drug Delivery across Nasal Epithelial Models

Cited by 13 publications

References 37 publications

Clozapine-Encapsulated Binary Mixed Micelles in Thermosensitive Sol–Gels for Intranasal Administration

Clozapine-Encapsulated Binary Mixed Micelles in Thermosensitive Sol–Gels for Intranasal Administration

Formulation of Chitosan Microparticles for Enhanced Intranasal Macromolecular Compound Delivery: Factors That Influence Particle Size during Ionic Gelation

Pre-referral intranasal artesunate powder for cerebral malaria: a proof-of-concept study

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