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Biomedical subjects

Y W Chien

Publications and source records attributed to Y W Chien.

At least 37 records · Page 2Linked to original sources
PubMed1996

Mutual hairless rat skin permeation-enhancing effect of ethanol/water system and oleic acid.

The mutual hairless rat skin permeation-enhancing effect of ethanol (EtOH)/water systems and oleic acid (OA) was investigated with model lipophilic (estradiol, progesterone, levonorgestrel) and hydrophilic drugs (zalcitabine, didanosine, zidovudine). The aqueous solubility and hairless rat skin permeation rate of each drug, saturated in various compositions of EtOH/water system (with and without OA), was determined at 37 degrees C. The hairless rat skin permeation rates of ethanol from EtOH/water systems (with and without OA) were also measured to investigate the skin permeation-enhancing mechanism of EtOH/water systems and OA. Both saturated solubility and steady-state permeation rates of each drug in EtOH/water systems increased exponentially as the volume fraction of ethanol increased, reached the maximum value, and then decreased with further increases in the ethanol volume fraction. Moreover, the hairless rat skin permeation rate of each drug had a good linear relationship with that of ethanol up to 70% (v/v) of ethanol in the EtOH/water system. The addition of OA in the EtOH/water system (70:30 and 60:40 for lipophilic and hydrophilic drugs, respectively) further enhanced the skin permeation rate of both ethanol and drugs. However, > 2.0% (v/v) OA was required to achieve the plateau level in the skin permeation rate of lipophilic drugs, whereas only 0.3% (v/v) OA was required for hydrophilic drugs. The skin permeation rate of ethanol also increased with the addition of OA in the EtOH/water systems (70:30 and 60:40), reached the plateau level with < 1.0% (v/v) OA, and did not significantly change with higher OA concentration. These results suggest that the addition of OA in the EtOH/water system is a useful method to enhance the hairless rat skin permeation rate of both hydrophilic and lipophilic drugs, with more enhancement for hydrophilic drugs.

Animals↗
PubMed1996

Prolonged immune response evoked by a single subcutaneous injection of microcapsules having a monophasic antigen release.

A model antigen, bovine serum albumin (BSA), was successfully incorporated into microcapsules fabricated from blends of poly(d,l-lactide-co-glycolide) and poly(d,l-lactide). The microcapsules possessed diameters ranging from 10 to 100 microns and exhibited a continuous monophasic release of the protein in-vitro for 3 weeks. They were found to enhance its immunogenicity, thereby potentiating the anti-BSA antibody response following a single subcutaneous injection in mice and rabbits. Enzyme-linked immunosorbent assays demonstrated that the microcapsules provoked high-titre and long-lived immunoglobulin G immune responses over a period of 192 days in mice. When rabbits were immunized by a single subcutaneous injection of BSA-loaded microcapsules, a high level of anti-BSA antibody was still present in the sera obtained at 17 weeks post-injection. The immunization protocol using the BSA-loaded microcapsules was superior to that using BSA dissolved in saline or adsorbed to alum. These microcapsules providing the controlled release of antigens may be valuable in designing better vaccine formulations.

Animals↗
PubMed1996

Day-night differences in the kinetics and dynamics of insulin: diabetic versus normal Yucatan minipigs.

Time-dependent variations in the pharmacokinetics and pharmacodynamics of insulin were studied at two times, 10:30 and 20:30 during the same day in normal and streptozotocin (STZ)-induced diabetic minipigs housed in L(06:00):D(18:00) using the intravenous insulin tolerance test. Following intravenous insulin (0.1 IU/kg) administration in normal minipigs, the time for the glucose level to reach nadir (tnadir) was significantly longer in the evening than the morning [(A.M.; 30.4 (+/- 2.4) vs. P.M.: 38.5 (+/- 3.3) min] (p < 0.01), although maximum reduction of glucose level (nadir) in the morning and evening was not significantly different [A.M.: (-70 (+/- 2) vs. P.M.: -65 (+/- 5) %]. The rate of glucose decline (Kin) was significantly decreased in the evening [A.M.: 5.33 (+/- 0.71) vs. P.M.: 4.44 (+/- 0.54) %dBG/min] (p < 0.01), and the integrated glucose-lowering response (ABCB) was significantly higher in the evening than the morning [A.M.: 3.18 (+/- 0.38) vs. P.M.: 4.52 (+/- 0.30) (g/dl)* min] (p < 0.01). The area under the plasma insulin concentration curve was increased significantly in the evening [A.M.: 2.26 (+/- 0.174) vs. P.M.: 2.74 (+/- 0.18) (mU/ml)* min], while the morning plasma insulin half-life did not differ significantly from that in the evening [A.M.: 4.79 (+/- 0.36) vs. P.M.: 5.47 (+/- 0.47) min]. After induction of diabetes by intravenous STZ injections, minipigs became diabetic, baseline blood glucose was observed to increase from the range of 45-55 to 200-250 mg/dl while plasma insulin levels decreased from 7-12 to 3-5 uU/ml. In the STZ-induced diabetic minipigs, a higher dose (0.2 IU/kg) was used in the intravenous insulin tolerance test in an attempt to normalize the high glucose levels. Following intravenous administration of insulin, the evening Kin and ABCB were significantly higher than they were in the morning [Kin = A.M.: 0.99 (+/- 0.25) vs. P.M.: 1.75 (+/- 0.44) %dBG/min (p < 0.01); ABCB = A.M.: 12.63 (+/- 1.91) vs. P.M.: 19.09 (+/- 5.43) (g/dl)* min (p < 0.01)]. However, there was no significant difference between tnadir and nadir values obtained in the morning and evening [tnadir = A.M.: 81.4 (+/- 9.2) vs. P.M.: 92.8 (+/- 13.7) min; nadir = A.M.: 39.6 (+/- 5.2) vs P.M.: 48.0 (+/- 9.0) %]. The pharmacodynamics and pharmacokinetics of IV insulin both were found to be highly dose-dependent (r > 0.90).

Animals↗
PubMed1996

Oramucosal delivery of LHRH: pharmacokinetic studies of controlled and enhanced transmucosal permeation.

Several transmucosal therapeutic systems (TmTs) were developed to study the enhanced/controlled delivery of luteinizing hormone-releasing hormone (LHRH) through oral mucosae for prolonged periods. TmTs is a track field-shaped bilayer mucoadhesive device consisting of fast-release and sustained-release layers. In vivo evaluations were performed in beagle dogs, and pharmacokinetic profiles were monitored to characterize the transmucosal permeation kinetics of LHRH delivered by the various TmTs formulations containing a stabilizer, cetylpyridinium chloride, and a permeation enhancer, such as bile salts, to enhance the stability and permeability of LHRH. The plasma LHRH concentrations were observed to reach the plateau level within 30 min and were maintained for 2 hr following application of TmTs, in contrast to a rapid elimination profile observed after IV administration. Addition of 5% bile salt into the fast-release layer was observed to produce an enhancement in the absorption rate, higher plateau plasma levels, and greater systemic bioavailability. Addition of pH modifiers was noted to affect the bile salt enhanced transmucosal delivery of LHRH. To prolong the plasma LHRH level, several loading doses of LHRH were incorporated into the sustained-release layer. The plasma levels were sustained and the area under the curve (AUC) values were found to be linearly dependent upon the combined loading doses of LHRH in the fast-release and sustained-release layers. Mucosal irritation was also measured, using buccal mucosa, and results were observed to be low and reversible for the single application. The results indicated that TmTs is relatively safe and capable of achieving enhanced and controlled transmucosal delivery of peptide drugs.

Absorption↗
PubMed1996

In vitro permeation study of a mucoadhesive drug delivery system for controlled delivery of nonoxynol-9.

A carbopol 934P-based drug delivery system (AmDDS) was developed to achieve the dual-controlled delivery of Nonoxynol-9 (N-9), a spermicidal agent, and EDTA, a potentiator of spermicidal activity. This gel-type system made intimate contact with vaginal mucosa and maintained an effective drug concentration within the vagina for a prolonged period of time. An existing mathematical model, based on a unilayer diffusion membrane, was applied for describing permeation of N-9 through vaginal mucosa. Vaginal permeation of N-9 from AmDDS was negligible over the initial 5 hr, then increased in a Q versus t pattern, but remained low. A relationship was observed between the permeation rate (Js) of drug through vaginal mucosa and the release flux (Q/t1/2) from AmDDS, which showed that the permeation rate (Js) increased with increased square of the release flux [(Q/t1/2)2] in a hyperbolic manner. This result indicated that release of N-9 from AmDDS is still the rate-limiting step at doses within the tested range. EDTA, at concentration of up to 0.32%, did not change the permeation rate of N-9 through vaginal mucosa. It is thus concluded that the developed AmDDS can control the intravaginal delivery of N-9 as well as its permeation through vaginal mucosa.

Adhesives↗
PubMed1996

Dual-controlled drug delivery across biodegradable copolymer. I. Delivery kinetics of levonorgestrel and estradiol through (caprolactone/lactide) block copolymer.

Four block copolymers of caprolactone (CL) and dl-lactide (LA) with varying weight fractions were synthesized by living polymerization in the presence of Al/Zn bimetallic alkoxide complex. The solubility of levonorgestrel (LNG) and estradiol (E2) in the copolymers was evaluated and found to increase exponentially with CL mole fraction. Their aqueous solubilities were also studied and observed to increase linearly with the concentration of benzalkonium chloride (BAC), a solubilizer. The kinetics of LNG and E2 permeation through the copolymer membranes were studied and observed to follow a zero-order kinetics, and the permeation rates obtained were noted to be a function of copolymer composition. The release kinetics through the copolymer matrix were also studied and noted to follow a matrix-diffusion process, and the release flux was found to be dependent on copolymer composition. Permeation rates and release fluxes at steady state as well as the permeability and solubility of LNG and E2 in the copolymers suggest that these permeation parameters are affected by copolymer composition, which increase as the CL/LA ratio in the copolymer was increased.

Biotransformation↗
PubMed1996

Systemic delivery of peptides and proteins across absorptive mucosae.

As therapeutic peptides and proteins become readily available through rapid advances in recombinant technology, and because rapid presystemic elimination renders them ineffective when administered orally, pharmaceutical scientists are faced with the challenge of delivering these macromolecules systemically; therefore, alternative routes of delivery need to be investigated. Transmucosal delivery through absorptive mucosae represents one of these alternatives. This route has the advantage of being noninvasive and of bypassing hepatogastrointestinal clearance. The absorptive mucosae that have been investigated for delivery of peptides and proteins include buccal, nasal, pulmonary, rectal, and vaginal. Nasal delivery has been studied extensively and has been the most successful--nasal sprays for buserelin, desmopressin, oxytocin, and calcitonin are already available commercially. In general, enzyme inhibitors and permeation enhancers need to be coadministered for successful delivery of these biopharmaceuticals. Classes of enhancers used for transmucosal delivery include bile salts, dihydrofusidates, cyclodextrins, surfactants, and chelating agents. Each of these agents exerts its enhancing effects by a different mechanism, and each has been associated with adverse effects. This article discusses the physiology of each of the mucosae used, the fundamentals of transmucosal delivery, and recent progress in systemic delivery of therapeutic peptides and proteins across each of the mucosae; in an effort to highlight principles of transmucosal delivery, it also discusses the transmucosal delivery of enkephalin, calcitonin, and insulin as case studies.

Absorption↗
PubMed1995

Intestinal absorption of dideoxynucleosides: characterization using a multiloop in situ technique.

The intestinal absorption of dideoxynucleosides was studied in rabbits, using a closed-loop mesenteric-sampling in situ technique developed in this laboratory, and the kinetic profiles were characterized. Each of the dideoxynucleosides exhibited different dependence on the intestinal regions studied: 3'-azido-2',3'-dideoxythymidine was best absorbed from the ileum, while 2',3'-dideoxyinosine and 2',3'-dideoxycytidine were preferentially absorbed from the jejunum. The results were validated by the mass-balance approach; the percent of drug retained in the intestinal lumen and that degraded at the intestinal pH, by colonic flora, in the intestinal tissue, and in plasma were assessed.

Animals↗
PubMed1995

A new bioassay for insulin in conscious rabbits by continuous measurement of glycemic responses.

Because of the substantial variability often observed in the determination of insulin potency by the United States Pharmacopeia (USP) bioassay method, a large number of rabbits are required in order to attain an accuracy of +/- 6% and each bioassay needs 2-3 weeks to be completed. In this report, an improved bioassay method has been developed. This bioassay was conducted in conscious healthy rabbits. The decline in blood glucose levels, following intravenous injection of an insulin preparation, was monitored (in uninterrupted manner) by the continuous glucose monitoring system developed. A glucose response curve was generated, and from this response curve, various pharmacodynamic parameters were easily determined. The whole procedure could be completed in 1 day and also achieved an accuracy where upon only one rabbit is needed to determine accurately the insulin potency. To validate the method, a total of nine healthy rabbits were studied to determine the inter- and intra-animal reproducibility. The values of insulin potency determined from four pharmacodynamic parameters were compared, and the potency calculated from the ABGC (area of the blood glucose response curve under baseline) was found to be the most accurate: a mean (+/- SEM) value of 102.3(+/- 1.2)% was determined by inter-animal study (n = 9) and a value of 100.6(+/- 1.3)% by intra-animal study (n = 4). The inter-bioassay variability among the random-dose bioassays was 1.2% for inter-animal and 1.3% for intra-animal studies. The insulin potency in an insulin sample determined by this bioassay had attained an overall mean (+/- SEM) value of 101.6(+/- 0.8)% (n = 17).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Transdermal delivery of dideoxynucleoside-type anti-HIV drugs. 1. Stability studies for hairless rat skin permeation.

The stability of dideoxynucleoside-type anti-HIV drugs in solution when in contact with hairless rat skin was investigated in order to study the feasibility of their transdermal delivery. The freshly excised dorsal region of hairless rat skin was mounted on Valia-Chien skin permeation cells, and both epidermis (donor) and dermis (receptor) were extracted with isotonic phosphate buffer (pH 7.4) at 37 degrees C for 24 h. Zalcitabine (DDC), didanosine (DDI), and zidovudine (AZT) were found to be stable in the extract of the epidermis at 37 degrees C for at least 30 h. However, DDC and DDI degraded in the extract of the dermis following first-order kinetics at both 25 and 37 degrees C, while AZT was stable at 37 degrees C for at least 30 h. The degradation mechanism(s) of DDC and DDI was (were) studied by analyzing HPLC chromatograms and by evaluating the drug stability in the extract which was filtered to remove any microbes. An unidentified peak produced by DDC in the dermis extract did not appear when the drug was added to the filtered extract, which suggested a bacterial degradation of DDC. On the other hand, DDI was unstable even in the filtered extract and produced a degradation product which corresponded to hypoxanthine, which suggested that a cutaneous enzyme is also involved in the degradation of DDI. DDC was stabilized by the addition of 0.01% (w/v) of an antibacterial agent, such as thimerosal or gentamicin, in the receptor solution, while DDI was stabilized by 0.01% (w/v) purine nucleoside phosphorylase inhibitor, i.e., p-chloromercuribenzoic acid. These results show the importance of stability studies when designing skin permeation experiments using hairless rat since compounds with similar chemical structures can have different stability profiles when in contact with hairless rat skin.

Administration, Cutaneous↗
PubMed1995

Effects of H+ liberated from hydrolytic cleavage of polyester microcapsules on their permeability and degradability.

Microcapsules prepared from blends of poly(d,l-lactide-coglycolide) with a lactide:glycolide ratio of 75:25 (PLGA75:25) and poly-(d,l-lactide) (PLA5000) or poly(d,l-lactic acid-co-glycolic acid) (PLGA5000) were dispersed in phosphate-buffered saline, and their hydrolytic rates were investigated. Using the Henderson-Hasselbalch equation and an L-lactic acid experiment, the concentration of hydrogen ions released into the bulk medium was calculated from the change in buffer pH. The rate of H+ formation was found to be dependent upon the polymer composition of the microcapsules. The incorporation of PLGA5000 or PLA5000 into PLGA75:25 microcapsules drastically enhanced hydrolytic rates of microcapsules and resulted in controlled release of hydrogen ions generated from carboxyl end groups of both intact and degrading polymers. In contrast to microcapsules prepared with PLGA75:25 only, which liberated a negligible amount of H+ ions after a 21-day incubation, the microcapsules prepared from polymer blends released approximately (19.2-42.0) (x10(-3)) mmol of H+ ions. It has been found that the amount of hydrogen ions liberated into the bulk can be used as a qualitative indicator to monitor the change in microcapsule permeability to protein as well as polymer degradation.

Capsules↗
PubMed1995

Transdermal delivery of zalcitabine: in vitro skin permeation study.

OBJECTIVE: To study the feasibility of transdermal delivery of anti-HIV drugs in order to maintain blood concentration within the therapeutic range for longer duration and to reduce the side-effects associated with high dose administration. DESIGN AND METHODS: The effects of vehicles and enhancers on the skin permeation rate of zalcitabine (ddC) were investigated to determine the maximum permeation rate attainable. In vitro skin permeation of ddC, saturated in various compositions of ethanol/tricaprylin or ethanol/water cosolvent system, with and without enhancer, was studied at 37 degrees C using freshly excised hairless rat skin and human cadaver skin as model skins. RESULTS: The skin permeation rate of ddC from both ethanol/tricaprylin and ethanol/water cosolvent system increased when increasing the volume fraction of ethanol and reached maximum values at 50-60% (vol/vol) of ethanol. Addition of 1.0% (vol/vol) of permeation enhancer, such as oleic acid or N-methyl-2-pyrrolidone, to the ethanol/tricaprylin (50:50) cosolvent system could not significantly increase the permeation rate of ddC. However, addition of 1.0% (vol/vol) of oleic acid in ethanol/water (60:40) cosolvent system dramatically enhanced the skin permeation rate of ddC with reduced lag time. Permeation rate of ddC increased with increasing oleic acid concentration up to 0.7% (vol/vol) in the ethanol/water (60: 40) cosolvent system, and reached a plateau with further addition of oleic acid. Although permeation rate of ddC across human cadaver skin (0.61 mg/cm2/h) was three times lower than that across hairless rat skin (1.88 mg/cm2/h), the maximum permeation rate of ddC attainable, using ddC saturated solution in ethanol/water (60: 40) cosolvent system containing 1.0% (vol/vol) oleic acid, was 4-5 times higher than the target rate (0.14 mg/cm2/h) to maintain the therapeutic blood level. CONCLUSION: The synergistic enhancement effect of ethanol and oleic acid can make transdermal delivery of ddC feasible.

Administration, Cutaneous↗
PubMed1993

Transmucosal delivery of methionine enkephalin. I: Solution stability and kinetics of degradation in various rabbit mucosa extracts.

To evaluate the feasibility of transmucosal delivery of methionine enkephalin (Tyr-Gly-Gly-Phe-Met; Met-Enk), it is important to first investigate its physicochemical and enzymatic stability. The kinetics of degradation of Met-Enk in aqueous solution was determined at pH 2.01-9.84 and 37-45 degrees C by high-performance liquid chromatography. The first-order rate constant (k) was calculated, and the log k-pH profile showed that Met-Enk is most stable at pH approximately 5.0. Various mucosae excised from rabbit were mounted on Valia-Chien permeation cells and exposed to isotonic phosphate buffer at physiologic pHs. Mucosal and serosal extracts were collected from the donor and receptor solutions, respectively. The degradation of Met-Enk in the extracts followed first-order kinetics, but no significant difference in the degradation rates was observed between mucosal and serosal extracts, regardless of the type of mucosa used. Degradation was most rapid in the extracts of rectal mucosa, followed by vaginal and nasal mucosae. The major metabolites were Des-Tyr-Met-Enk and Tyrosine (Tyr), indicating the enzymatic hydrolysis by aminopeptidases. However, the data also suggested that dipeptidyl peptidase and dipeptidyl carboxypeptidase could play some roles in the degradation of Met-Enk. The degradation pathways of Met-Enk were further explored by concomitantly determining the formation of smaller metabolites of primary hydrolytic fragments of Met-Enk in the mucosal extracts.

Amino Acid Sequence↗
PubMed1993

Transmucosal delivery of leucine enkephalin: stabilization in rabbit enzyme extracts and enhancement of permeation through mucosae.

Leucine enkephalin (Tyr-Gly-Gly-Phe-Leu; Leu-Enk) is a naturally occurring peptide that has been shown to have pain modulating properties. To evaluate the feasibility of using various absorptive mucosae as a route of systemic delivery, the stability of Leu-Enk and the effect of enzyme inhibitors (e.g., amastatin, EDTA, and thimerosal) on stabilization and permeation of Leu-Enk through rabbit mucosae in the presence of dihydrofusidates were investigated. Enzymes in the nasal, rectal, and vaginal mucosae were extracted and Leu-Enk (50 micrograms/mL) was added to each of the enzyme extracts and incubated to determine the kinetics and mechanism of degradation. The rate of degradation in the extracts in the absence of inhibitors followed the order: rectal > vaginal > nasal. Whereas EDTA had the best stabilizing effect on Leu-Enk, thimerosal was the best stabilizer for the degradation intermediates. A combination of amastatin (50 microM), EDTA (5 mM), and thimerosal (50 microM) had the greatest stabilizing effect on Leu-Enk and its degradation intermediates. For permeation studies, each mucosa was mounted onto a Valia-Chien permeation cell with Leu-Enk (200 micrograms/mL) in isotonic phosphate buffer (as donor solution). The enhancers used for the study were sodium tauro-dihydrofusidate (STDHF), sodium glycodihydrofusidate (SGDHF), and phosphato-dihydrofusidate (PHDHF). The greatest effect was achieved by PHDHF for all the mucosae. STDHF had a significant effect only on the rectal permeation, whereas SGDHF had significant effects on rectal and vaginal mucosae. Mechanisms by which the dihydrofusidates enhance permeating may involve micelle formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Hydrogel-based iontotherapeutic delivery devices for transdermal delivery of peptide/protein drugs.

Hydrogels were synthesized as the drug reservoir matrix for peptide-based pharmaceuticals, and the iontophoretic release and transdermal delivery of three model peptides, insulin, calcitonin, and vasopressin, from these hydrogel-based iontotherapeutic devices were investigated. The swelling behavior of polyacrylamide-type hydrogel as a function of its monomer and cross-linker concentration was studied, and a hydrogel with minimal swelling was synthesized. The release of peptides from the hydrogel matrix was found to follow a Q vs t1/2 relationship under passive diffusion conditions, which shifted to a Q vs t relationship under iontophoresis-facilitated transport. The release flux (dQ/dt) of peptides was observed to decline when the electric current was turned off and was resumed when the current was turned on, thus allowing for modulation of drug release by varying the application parameters of iontophoresis-facilitated transport. The permeability coefficients for these peptides across the hairless rat skin were evaluated using the hydrogel formulations prepared from polyacrylamide, p-HEMA, and carbopol. A rank order of vasopressin > calcitonin > insulin was obtained in accordance with the order of molecular size.

Acrylic Resins↗
PubMed1991

Enhanced skin permeability for transdermal drug delivery: physiopathological and physicochemical considerations.

To deliver drugs through the skin for systemic medication, the skin permeability needs enhancing by either modifying the drug molecules, or applying skin permeation enhancers to reduce the barrier property of the skin. Traditionally, the enhancement of skin permeability is considered as the result from the improvement of the lipophilicity of drugs and the partition of drugs into the skin, or from the direct actions of skin permeation enhancers on the chemical structure and/or composition of lipids and proteins in the stratum corneum. However, on the other hand, the skin also responds to drugs and/or skin permeation enhancers physiopathologically via its inflammatory and immune reaction. The physiopathological responses of the skin can also induce the changes in the chemical structure and composition of lipids and proteins in the skin. Therefore, the possible role of physiopathological responses of the skin in the enhanced skin permeability should be concerned.

Administration, Cutaneous↗
PubMed1990

Characterization of the barrier properties of mucosal membranes.

The barrier properties of the nasal, rectal, and vaginal membranes were investigated in the rabbit by comparing physical characteristics and permeability to model hydrophilic and lipophilic compounds. It was found that the nasal, rectal, and vaginal mucosae differ in their physical characteristics and interactions. The nasal mucosa had the highest in vitro transport of both the model hydrophilic compound, mannitol, and the model lipophilic compound, progesterone. Although the nasal mucosa was found to have some hydrophilic character, it appears that these mucosae are primarily lipophilic in nature. The role of the lipid domain in the barrier properties of these mucosal membranes was investigated using progesterone and a series of its hydroxyprogesterone analogues. Membrane permeability was found to decrease as the order of hydrophilicity of the progestins increased, indicating that the lipid domain plays an important role in the barrier function of these membranes. The changes observed in the physical properties and permeability of the mucosal membranes after extraction of the lipids also demonstrated the importance of the lipid domain in the maintenance of the mucosal barrier.

Animals↗