Untitled

Schipper, Nicolaas; Olsson, Susanne; Hoogstraate, Janet; deBoer, A.G.; Vårum, Kjell M.; Artursson, Per

doi:10.1023/a:1012160102740

Cited by 525 publications

(99 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, PLA appears to increase the paracellular permeability as reported in monolayers such as Caco-2 and MDCK cells and excised rabbit nasal epithelium. 14,[21][22][23] In addition, PLA induced same degree of factor enhancement for both pyridoxamine and FD-4 regardless of the difference in their molecular size (Tables 1, 2). Since our simulation uniformly increased the Papp of hydrophilic compounds with a broadly distributed molecular weight when the area fraction of the permeation pathway was increased (unpublished data), PLA may increase area fraction of the permeation pathway for pyridoxamine and FD-4.…”

mentioning

confidence: 82%

Effects of Poly-L-arginine on the Permeation of Hydrophilic Compounds through Surface Ocular Tissues

Nemoto¹,

Takahashi²,

Kobayashi³

et al. 2006

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Drugs that are topically applied to the cul-de-sac enter the intraocular area via both corneal and noncorneal pathways which are composed of cornea and conjunctiva-sclera, respectively.1) Although the corneal pathway is thought to be the primary route of intraocular entry for most drugs, penetration via the noncorneal pathway can also be important for the penetration of drugs which are poorly absorbed across the cornea. 2,3) In addition, the noncorneal pathway could be more important than the corneal pathway for the delivery of drugs to the posterior segment of the eye. 2,3)The first barrier to intraocular entry via the corneal and noncorneal pathways is the cornea and conjunctiva, respectively. These epithelial tissues are known to have tight junctions that act as a barrier in the paracellular spaces. 4,5) Because of this barrier structure in the epithelia, insufficient drug may be absorbed after instillation. Thus, subconjunctival and intravitreous injections are generally used in ocular pharmacotherapy.1) These invasive methods may not be acceptable to many patients and could potentially increase the risk of infection.6) In order to obtain a simpler and more acceptable form of application, the development of effective instilled formulations would be a major improvement. A number of ocular penetration enhancers, including calcium chelator (EDTA) and bile salts, have already been investigated, and it was found that those enhancers increased the apparent permeability coefficient (Papp) of FITC-dextran (MW: 4000, FD-4) by 2.9-to 15.5-fold in excised cornea and conjunctiva.7) However, these enhancers might not be acceptable from a safety point of view, because the following were observed: severe epithelial damage, such as a change in cellular morphology produced by EDTA and deoxycholate in the cornea, 8) leakage of cytosolic proteins produced by EDTA in the rectum, 9) and permeabilization caused by dissolution of the plasma membrane produced by bile salts. 10)Recently, a novel type of penetration enhancer has been developed for mucosal drug delivery. Illum et al. 11) showed that the polycationic compound, chitosan, greatly enhanced the absorption of insulin across the nasal mucosa in rats and sheep. Basic amino acid polymers such as poly-L-arginine (PLA) and poly-L-lysine (PLL) are also shown to effectively increase permeability of various compounds in nasal, tracheal, and kidney epithelia. [12][13][14] Although it is reported that PLL induces potential epithelial damages in tracheal epithelium, 13) PLA appears to enhance the absorption of hydrophilic molecules in mucosal tissues without producing any obvious epithelial changes, such as morphological alteration, leakage of cytosolic proteins, and release of phospholipids from the plasma membrane.15,16) Thus, PLA is considered to be an ideal permeation enhancer for epithelial drug delivery including ocular delivery.The purpose of the present study was to examine the enhancing effect of PLA on the permeability of hydrophilic compounds through the ocular epithelia....

show abstract

mentioning

confidence: 82%

Effects of Poly-L-arginine on the Permeation of Hydrophilic Compounds through Surface Ocular Tissues

Nemoto¹,

Takahashi²,

Kobayashi³

et al. 2006

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…This effect of chitosan might be a result of its film forming ability and absorption enhancing properties. [15][16][17] Film formation ensures that the skin is covered, which retains moisture and thus contributes to opening of the pores of the skin for drug entry. In addition, skin hydration causes swelling of keratinocytes, affecting lipid packing in the stratum corneum.…”

Section: Resultsmentioning

confidence: 99%

DA 5505: A Novel Topical Formulation of Terbinafine That Enhances Skin Penetration and Retention

Thapa

Han

Park

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Topical fungal infections can become severe if left untreated. Efficient treatment modalities for topical fungal infections aid the penetration of antifungal agents deep into viable skin layers. Terbinafine is a fungicidal agent that inhibits ergosterol, an essential fungal component. The main objective of this study was to evaluate skin permeation and retention of a terbinafine-loaded solution containing chitosan as a film former. Comparative assessment of skin permeation and retention was performed using a prepared formulation (DA 5505) and marketed formulations of terbinafine in murine and porcine skin. To mimic fungal infection of skin, keratinized skin was induced in NC/Nga mice. In comparison with the marketed formulations, DA 5505 exhibited significantly better skin permeation. The flux, permeation coefficient, and enhancement ratio of terbinafine were remarkably increased by DA 5505 in comparison with the marketed formulations, and lag time was dramatically reduced. DA 5505 significantly increased cumulative terbinafine retention in viable skin layers in comparison with the marketed solution, suggesting enhanced efficacy. Furthermore, DA 5505 exhibited superior skin permeation in normal skin and keratinized skin. Thus, the DA 5505 formulation has the potential to effectively deliver terbinafine to superficial and deep cutaneous fungal infections.

show abstract

“…32,33 Further, CS posses good mucoadhesive properties and have the ability to improve the transport of hydrophilic drugs across intestinal epithelium by opening tight intestinal epithelium. 34 However, CS was selected for the present study mainly due to their ability to form gel upon contact with anionic polymers/low molecular weight counter ions. CS was utilized as a counter ion for the preparation of anionic PMAA microparticles, and intermolecular interactions between MAA-CS was responsible for the generation of microparticles during the process, since little success was obtained with the process tried in the absence of CS.…”

Section: Resultsmentioning

confidence: 99%

Interpolymer complex microparticles based on polymethacrylic acid‐chitosan for oral insulin delivery

Sajeesh

Sharma

2005

J of Applied Polymer Sci

View full text Add to dashboard Cite

ABSTRACT:In the present study, microparticles composed of polymethacrylic acid-chitosan (PMAA-CS) were prepared by a novel interionic gelation method. Free-radical polymerization of methacrylic acid was carried out in the presence of CS, using a water-soluble initiator, and application of these microparticles toward oral insulin delivery was evaluated. Microparticles obtained were characterized by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) studies. From SEM studies, it was observed that microparticles had an aggregated morphology with size ϳ20 m, while FTIR confirmed the presence of ionic interaction between PMAA and CS chains. Protein loading was done by diffusion filling method, and from in vitro release study, it was observed that insulin-loaded microparticles displayed a pH depended release profile at alkaline/acidic pH. Microparticles exhibited sustained release of insulin for 3-4 h at neutral pH, and enzyme linked immunosorbent assay (ELISA) proved that encapsulated protein maintained 100% biological activity at neutral pH. Preliminary study suggests that these microparticles can serve as good candidate for oral protein delivery.

show abstract

Untitled

Cited by 525 publications

References 6 publications

Effects of Poly-L-arginine on the Permeation of Hydrophilic Compounds through Surface Ocular Tissues

Effects of Poly-L-arginine on the Permeation of Hydrophilic Compounds through Surface Ocular Tissues

DA 5505: A Novel Topical Formulation of Terbinafine That Enhances Skin Penetration and Retention

Interpolymer complex microparticles based on polymethacrylic acid‐chitosan for oral insulin delivery

Contact Info

Product

Resources

About