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Asada, Hiroyuki; Douen, Takayuki; Mizokoshi, Yoshiko; Fujita, Takuya; Murakami, Masahirô; Yamamoto, Akira; Muranishi, Shozo

doi:10.1023/a:1018928613837

Cited by 70 publications

(6 citation statements)

References 23 publications

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“…The lumen of the small intestine was washed with 20 mL of PBS. The collected solution was treated with two volumes of methylene chloride to eliminate any lipids that might interfere with HPLC analysis of INS 34. The lipid extraction procedure was repeated 5 times.…”

Section: Methodsmentioning

confidence: 99%

<p>Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles</p>

Alsulays

Anwer

Soliman

et al. 2019

IJN

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PurposeThis study evaluated the stereoisomeric effect of L- and D-penetratin—cell-penetrating peptides (CPPs)—incorporated insulin-loaded solid lipid nanoparticles (INS-SLNs) on the bioavailability (BA) of oral insulin (INS).MethodsInsulin-loaded solid nanoparticles, L-penetratin-INS-SLNs (LP-INS-SLNs), and D-penetratin-INS-SLNs (DP-INS-SLNs) were formulated by double emulsification. The developed SLNs were evaluated for particle size, zeta potential (ZP), and drug encapsulation and subjected to differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and evaluated for stability against enzymatic degradation in rat intestinal fluid. Finally, the SLNs were administered to rats to evaluate the BA of INS-SLNs that contained L- and D-penetratin.ResultsThe mean particle size, PDI, and ZP values of INS-SLNs, LP-INS-SLNs, and DP-INS-SLNs ranged from 618.5 to 973.0 nm, 0.227 to 0.734, and −17.0 to −23.7 mV, respectively. The encapsulation efficiency (%EE) and drug loading (%DL) of INS-SLNs, LP-INS-SLNs, and DP-INS-SLNs ranged from 59.03% to 67.42% and from 1.62% to 1.82%, respectively. Differential scanning calorimetry and FTIR analyses indicated that INS was successfully encapsulated in SLNs. Enzymatic degradation of DP-INS-SLNs was slower in intestinal fluid, and the half-life (t1/2) was significantly prolonged, compared to all other SLNs. The pharmacological availability (PA) and BA of orally administered LP-INS-SLNs, which were the most effective SLNs, were 13.1% and 15.7% relative to s.c. administration, respectively.ConclusionPenetratin stereochemistry significantly impacted oral BA of INS-SLNs, which are promising carriers for oral INS administration.

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Section: Methodsmentioning

confidence: 99%

<p>Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles</p>

Alsulays

Anwer

Soliman

et al. 2019

IJN

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“…The samples collected were analyzed using a computer-controlled gradient HPLC system (Hitachi 7000, Japan) as reported previously. 25) In Vivo Studies Diabetes was induced in Wistar rats by intraperitoneal injection of streptozotocin (50 mg/kg body weight). The plasma glucose level (PGL) was determined at 2 and 3 weeks to ensure that diabetes had been induced.…”

Section: Methodsmentioning

confidence: 99%

Transdermal Delivery of Insulin Using Trypsin as a Biochemical Enhancer

Quan

Zang

et al. 2008

Biological & Pharmaceutical Bulletin

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There are 30 million patients with diabetes mellitus worldwide, and 1.2 million new patients are diagnosed each year, including a growing number of children and young adults. 1)However, insulin has been administered only by parenteral routes for the therapeutic control of type 1 diabetes; many patients typically require injections of insulin a minimum of two to three times per day. To improve patient convenience and compliance, alternative routes have been investigated including nasal, oral, transdermal, buccal, ocular, rectal, and vaginal pathways. 2) Transdermal delivery of insulin can prevent its metabolization and the first-pass effect and may thus be an optimal route of administration. However, delivery of large molecules by the transdermal route is also limited by the unique bioarchitecture of skin, which has primarily evolved as a protective barrier against the entry of microorganisms and water.3)The stratum corneum (SC) barrier can be partially overcome by disruption of the lipid structure using fatty acids and surfactants as chemical penetration enhancers. [4][5][6] However, these enhancers are only useful for small molecules, 6,7) and it is difficult to achieve meaningful permeation of large peptides. Most recent research has focused on the use of electrical energy to increase drug flux across the skin, including techniques such as iontophoresis, sonophoresis, electroporation, etc. [8][9][10] Unfortunately, the large, complex, and relatively uncharged insulin molecule still cannot across the intercellular lipid layer of the SC. The transport rate of hexameric insulin by iontophoresis across mouse skin has been low and variable.11) Monomeric insulin analogues carrying two additional negative charges have demonstrated transport rates 50-100-fold higher than those of hexameric insulin. However, the quantity of delivery is still not sufficiently high to provide an effective basal insulin level (1 IU/h). 11)To overcome the barrier presented by the SC, proteolytic enzymes maybe used as skin penetration enhancers because their action is highly specific toward proteins and their molecular size is too large to permeate the viable epidermis. Such enzymes perhaps alter skin permeability by provoking biochemical and metabolic events within skin. For more than 50 years, proteolytic enzymes such as trypsin have been extensively used in laboratory settings for in vitro epidermal separation and keratinocyte isolation.12-15) The unique ability of proteases to cause selective epidermal separation has been in part explained by the proteolytic degradation of desmosomal proteins in the SC, which leads to cell dissociation. 16,17) Recently, several endogenous proteases occurring in the epidermis have been found to play important roles in regulating epidermal cell desquamation.18-21) Based on these findings, several therapeutic applications have been attempted for wound debridement and epidermal ablation. [22][23][24] However, no studies have examined the use of such proteolytic enzymes as a penetration enhancers for t...

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“…The luminal contents of the GI were prepared according to the method of Asada et al 23 Rats were euthanized with an overdose intraperitoneal injection of urethane, and the GI was excised. The luminal contents of the stomach were collected by flushing with 5 ml of artificial gastric juice (pH 1.2), and the contents of the duodenum, jejunum, ileum and colon were collected by flushing with 5 ml physiological saline.…”

Section: Preparation Of Luminal Contents and Mucosal Subcellular Fracmentioning

confidence: 99%

Synthesis and Cathodoluminescence of β-Ga₂O₃ Nanowires with Holes

Wang

Dai²,

Zhang³

et al. 2008

j nanosci nanotechnol

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CyA was prepared into CyA Eudragit S100 nanoparticles (CyA-S100 NP) and the mechanisms of CyA-S100 NP improving the CyA absorption in gastrointestinal tract (GI) were studied systematically in rats. In the GI distribution study, the emptying rates of CyA-S100 NP in duodenum, jejunum, ileum and colon were all lower than these of Neoral, while in stomach, it was larger than that of Neoral. In in situ recirculating intestine perfusion experiment, the largest absorption in CyA-S100 NP group occurred in ileum while that in Neoral group arised in duodenum. The sequence of (AUC0-240 min)/A for CyA-S100 NP and Neoral group was ileum > duodenum > jejunum > colon and duodenum > jejunum > ileum > colon, respectively. CyA in nanoparticles degradated by luminal contents and subcellular fractions were more slowly than these in Neoral, suggesting the significant protect effect of nanoparticles. Mucoadhesion study in small intestine showed that among all the parts of intestine, CyA-S100 NP exhibited larger mucoadhesive characteristics than Neoral microemulsion. The sequence of mucoadhesion for CyA-S100 NP group was duodenum > ileum > jejunum and colon, while that for Neoral group was duodenum > ileum, jejunum and colon, suggesting different site-specific behaves. These results illustrated that nanoparticles increased the absorption of CyA could be attributed to fast stomach empting rate, absorption site specific, small degradation rate by luminal contents, high bioadhension of nanoparticles to intestine mucosa and the use of P-Glycoprotein inhibitor if there is any. This investigation is helpful for the dosage form design for other peptide or protein drugs.

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Untitled

Cited by 70 publications

References 23 publications

<p>Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles</p>

<p>Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles</p>

Transdermal Delivery of Insulin Using Trypsin as a Biochemical Enhancer

Synthesis and Cathodoluminescence of β-Ga₂O₃ Nanowires with Holes

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Untitled

Cited by 70 publications

References 23 publications

<p>Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles</p>

<p>Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles</p>

Transdermal Delivery of Insulin Using Trypsin as a Biochemical Enhancer

Synthesis and Cathodoluminescence of β-Ga2O3 Nanowires with Holes

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Synthesis and Cathodoluminescence of β-Ga₂O₃ Nanowires with Holes