The lipid composition of porcine epidermis and oral epithelium

Squier, Christopher A.; Cox, Patrick; Wertz, Philip W.; Downing, Donald T.

doi:10.1016/0003-9969(86)90006-3

Cited by 51 publications

(19 citation statements)

References 34 publications

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“…In both mucosal epithelia ( 17), and in the epidermis of marine cetaceans ( 18), both ofwhich have less competent barriers than epidermis, the ratio of glucosylceramides to ceramides remains high. Moreover, fl-glucosidase levels are lower in oral mucosa than in the epidermis of the same species ( 19).…”

Section: Introductionmentioning

confidence: 99%

Processing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability barrier function.

Holleran¹,

Takagi²,

Menon³

et al. 1993

J. Clin. Invest.

245

201

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The interstices of the mammalian stratum corneum contain lipids in a system of continuous membrane bilayers critical for the epidermal permeability barrier. During the transition from inner to outer stratum corneum, the content of polar lipids, including glucosylceramides, decreases while ceramide content increases. We investigated whether inhibition of glucosylceramide hydrolysis would alter epidermal permeability barrier function. Daily topical applications of bromoconduritol B epoxide (BrCBE) to intact murine skin selectively inhibited fl-glucocerebrosidase, increased glucosylceramide content of stratum corneum with ceramide content remaining largely unchanged, and caused a progressive, reversible decrease in barrier function. Histochemistry of inhibitor-treated epidermis revealed persistence of periodic acid-Schiff-positive staining in stratum corneum cell membranes, consistent with retention of hexose moieties. Electron microscopy of inhibitor-treated samples revealed no evidence of toxicity or changes in the epidermal lipid delivery system. However, immature membrane structures persisted in the intercellular spaces throughout the stratum corneum, with reappearance of mature membrane structures progressing outward from the lower stratum corneum upon termination of BrCBE. Finally, the induced barrier abnormality was not reversed by coapplications of ceramide. These data demonstrate that glucosylceramide hydrolysis is important in the formation of the epidermal permeability barrier, and suggest that accumulation of glucosylceramides in stratum corneum intercellular membrane domains leads to abnormal barrier function. (J. Clin. Invest. 1993.91:1656-1664

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Section: Introductionmentioning

confidence: 99%

Processing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability barrier function.

Holleran¹,

Takagi²,

Menon³

et al. 1993

J. Clin. Invest.

245

201

View full text Add to dashboard Cite

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“…The parameters governing the release of the dissolved material are thus the rate at which the interface moves, the diffusivity of the dissolved material in the rubbery polymer, and the total length of the diffusional path (57). In this kind of transport, the polymer relaxation is the ratelimiting step to water transport (58).…”

Section: Model-dependent Methodsmentioning

confidence: 99%

“…In this case, the enhancement in drug permeation occurred because cyclodextrin acted as an enhancer of permeation. It is known that this cyclodextrin is more hydrophobic, can permeate the buccal mucosa and form inclusion complexes with hydrophobic molecules, such as lipids from the cellular membrane (58,59). It can also modify the buccal mucosa permeability and act as a penetration enhancer in the buccal route.…”

Section: Permeation Studiesmentioning

confidence: 99%

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A Comprehensive Development Strategy in Buccal Drug Delivery

2010

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Abstract. This work combines several methods in an integrated strategy to develop a matrix for buccal administration. For this purpose, tablets containing selected mucoadhesive polymers loaded with a model drug (omeprazole), free or in a complexed form with cyclodextrins, and in the absence and presence of alkali agents were subjected to a battery of tests. Mucoadhesion studies, including simple factorial analysis, in vitro release studies with both model-dependent and model-independent analysis, and permeation studies were performed. Mucoadhesive profiles indicated that the presence of the drug decreases the mucoadhesion profile, probably due its hydrophobic character. In tablets loaded with the drug complexed with β-cyclodextrin or methyl-β-cyclodextrin, better results were obtained with the methylated derivative. This effect was attributed to the fact that in the case of β-cyclodextrin, more hydroxyl groups are available to interact with the mucoadhesive polymers, thus decreasing the mucoadhesion performance. The same result was observed in presence of the alkali agent (L-arginine), in this case due to the excessive hydrophilic character of L-arginine. Drug release from tablets was also evaluated, and results suggested that the dissolution profile with best characteristics was observed in the matrix loaded with omeprazole complexed with methyl-β-cyclodextrin in the presence of L-arginine. Several mathematical models were applied to the dissolution curves, indicating that the release of the drug, in free or in complexed state, from the mucoadhesive matrices followed a super case II transport, as established on the basis of the Korsmeyer-Peppas function. The feasibility of drug buccal administration was assessed by permeation experiments on porcine buccal mucosa. The amount of drug permeated from mucoadhesive tablets presented a maximum value for the system containing drug complexed with the methylated cyclodextrin derivative in presence of L-arginine. According to these results, the system containing the selected polymer mixture and the drug complexed with methyl-β-cyclodextrin in presence of L-arginine showed a great potential as a buccal drug delivery formulation, in which a good compromise among mucoadhesion, dissolution, and permeation properties was achieved.

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“…These hydrophobic cyclodextrins act as absorption enhancers, probably, by transiently changing membrane perme-ability, overcoming the aqueous diffusion barrier and opening tight junctions [12]. During cell differentiation process in buccal mucosa, small organelles called membrane coating granules (MCGs) composed of non-lamellar lipid sacks are formed in intercellular spaces of the non-keratinized regions [13,14]. These MCGs, first observed in epidermis, are not different from those observed in the skin and are believed to provide an intercellular permeability barrier to buccal mucosa [15].…”

Section: Introductionmentioning

confidence: 99%

In vitro evaluation of natural and methylated cyclodextrins as buccal permeation enhancing system for omeprazole delivery

Figueiras

Hombach

Veiga

et al. 2009

European Journal of Pharmaceutics and Biopharmaceutics

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Omeprazole Permeation Stability a b s t r a c tIn this work the enhancing effect of cyclodextrins on the buccal permeation of a hydrophobic model drug, omeprazole was studied. First, the influence of the complexation with cyclodextrins in the absence and in the presence of an alkali agent, L-arginine, on the drug stability was checked at neutral conditions since omeprazole alone is only stable in basic conditions. In vitro transbuccal permeation of omeprazole non-complexed and complexed with b-and methyl-b-cyclodextrin and in presence of L-arginine was examined using freshly obtained porcine buccal mucosa. Tissue viability after incubation with sample solutions was assessed using a MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) biochemical assay and histological evaluation. The toxicity of the sample solutions on buccal mucosa was evaluated by measuring lactate dehydrogenase activity. The present results show that complexation with cyclodextrins increases drug stability at neutral conditions; furthermore, L-arginine contributed to higher drug stability. Permeation studies indicate an increase on drug permeation in complexed form of 1.1-and 1.7-fold for b-cyclodextrin and methyl-b-cyclodextrin, respectively. The presence of L-arginine increases drug permeation 1.4-fold in omeprazole complexed with b-cyclodextrin and 2.4-fold in the inclusion complex formed with methyl-b-cyclodextrin. The cell viability of the buccal mucosa after a 3 h incubation period, with all sample solutions, remained around 70% and lactate dehydrogenase assay showed that studied cyclodextrins, even in the presence of an alkali agent are not cytotoxic for porcine buccal mucosa. Histological evaluation of the tissue demonstrated that the buccal epithelium remains viable after 3 h of incubation with sample solutions.

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The lipid composition of porcine epidermis and oral epithelium

Cited by 51 publications

References 34 publications

Processing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability barrier function.

Processing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability barrier function.

A Comprehensive Development Strategy in Buccal Drug Delivery

In vitro evaluation of natural and methylated cyclodextrins as buccal permeation enhancing system for omeprazole delivery

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