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Tenma, Takehiro; Yodoya, Etsuo; Tashima, Shigeru; Fujita, Takuya; Murakami, Masahirô; Yamamoto, Akira; Muranishi, Shozo

doi:10.1023/a:1018983511247

Cited by 38 publications

(4 citation statements)

References 8 publications

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“…Compared to tetragastrin (TG), acyl, caproyl and lauroyl derivatives of TG have shown marked increase in gastric acid secretion following administration into the large intestinal loop. This increased activity is due to improved permeation of TG from the large intestine (Tenma et al, 1993). In another study, Wang et al synthesized lipidized salmon calcitonin (REAL–sCT) conjugate by ‘reversible aqueous lipidization’ (REAL) technology using N -palmitoyl cysteinyl 2-pyridyl disulfide as a lipidizing reagent (Wang et al, 2003).…”

Section: Other Approaches To Enhance the Oral Delivery Of Peptide mentioning

confidence: 99%

Approaches for enhancing oral bioavailability of peptides and proteins

Renukuntla

Vadlapudi

Patel

et al. 2013

International Journal of Pharmaceutics

563

331

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Oral delivery of peptide and protein drugs faces immense challenge partially due to the gastrointestinal (GI) environment. In spite of considerable efforts by industrial and academic laboratories, no major breakthrough in the effective oral delivery of polypeptides and proteins has been accomplished. Upon oral administration, gastrointestinal epithelium acts as a physical and biochemical barrier for absorption of proteins resulting in low bioavailability (typically less than 1–2%). An ideal oral drug delivery system should be capable of a) maintaining the integrity of protein molecules until it reaches the site of absorption, b) releasing the drug at the target absorption site, where the delivery system appends to that site by virtue of specific interaction, and c) retaining inside the gastrointestinal tract irrespective of its transitory constraints. Various technologies have been explored to overcome the problems associated with the oral delivery of macromolecules such as insulin, gonadotropin-releasing hormones, calcitonin, human growth factor, vaccines, enkephalins, and interferons, all of which met with limited success. This review article intends to summarize the physiological barriers to oral delivery of peptides and proteins and novel pharmaceutical approaches to circumvent these barriers and enhance oral bioavailability of these macromolecules.

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Section: Other Approaches To Enhance the Oral Delivery Of Peptide mentioning

confidence: 99%

Approaches for enhancing oral bioavailability of peptides and proteins

Renukuntla

Vadlapudi

Patel

et al. 2013

International Journal of Pharmaceutics

563

331

View full text Add to dashboard Cite

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“…DHT-Gln-Leu-Pro-Gly, lipid cholesterol [17,35]. ‡,* Dimyristoylphosphatidylethanolamine (DMPE) showed a significantly greater amount of acid secretion than TG, which was explained by the improved absorption of Cap-TG [8].…”

Section: Cholesteryl Groupmentioning

confidence: 99%

“…Hence, polymers containing attached sugars and drug molecules can be targeted to the liver. Polymers that were used as carriers R (CH 3 ) 8 CO NH Cys Tyr Phe Gln Asn Cys Pro Arg Gly NH2 R= Glucose, Mannose, 2-deoxy-glucose Fig. (3).…”

Section: Hepatic Targetingmentioning

confidence: 99%

Lipid, Sugar and Liposaccharide Based Delivery Systems

Wong

Tóth

2001

CMC

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Although there are formidable barriers to the oral delivery of biologically active drugs, considerable progress in the field has been made, using both physical and chemical strategies of absorption enhancement. A possible method to enhance oral absorption is to exploit the phenomenon of lipophilic modification and mono and oligosaccharide conjugation. Depending on the uptake mechanism targeted, different modifications can be employed. To target passive diffusion, lipid modification has been used, whereas the targeting of sugar transport systems has been achieved through drugs conjugated with sugars. These drug delivery units can be specifically tailored to transport a wide variety of poorly absorbed drugs through the skin, and across the barriers that normally inhibit absorption from the gut or into the brain. The delivery system can be conjugated to the drug in such a way as to release the active compound after it has been absorbed (i.e. the drug becomes a prodrug), or to form a biologically stable and active molecule (i.e. the conjugate becomes a new drug moiety). Examples where lipid, sugar and lipid-sugar conjugates have resulted in enhanced drug delivery will be highlighted in this review.

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“…For example, lauric acid (C12) was attached to the N terminus of thyrotropin-releasing hormone (TRH), which resulted in significantly increased penetration across the upper small intestine compared to the parent peptide in an in vitro everted sac experiment . A captoyl−tetragastrin conjugate produced significantly increased acid secretion in rats compared to the native tetragastrin . We have demonstrated previously that the conjugation of TRH and luteinizing hormone releasing hormone (LHRH) with one or two lipoamino acids (Laas) increased the peptides' half-lives in a homogenate of human intestinal epithelial cells by ∼30-fold from only 2−5 min to 1−3 h, and in vivo experiments in rats demonstrated a significant increase in the stability and oral uptake of the peptide conjugates …”

Section: Introductionmentioning

confidence: 99%

Synthesis, Structure Elucidation, in Vitro Biological Activity, Toxicity, and Caco-2 Cell Permeability of Lipophilic Analogues of α-Conotoxin MII

et al. 2003

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The alpha-conotoxin MII is a two disulfide bridge containing, 16 amino acid long peptide toxin isolated from the marine snail Conus magus. This toxin has been found to be a highly selective and potent inhibitor of neuronal nicotinic acetylcholine receptors (nAChRs) of the subtype alpha3beta2. To improve the bioavailability of this peptide, two lipidic analogues of MII have been synthesized, the first by coupling 2-amino-d,l-dodecanoic acid (Laa) to the N terminus (LaaMII) and the second by replacing Asn5 in the MII sequence with this lipoamino acid (5LaaMII). Both lipidic linear peptides were then oxidized under standard conditions. (1)H NMR shift analysis of these peptides and comparison with the native MII peptide showed that the tertiary structure of the N-conjugated analogue, LaaMII, was consistent with that of the native conotoxin, whereas the 5LaaMII analogue formed the correct disulfide bridges but failed to adopt the native helical tertiary structure. The N terminus conjugate was also found to inhibit nAChRs of the subtype alpha3beta2 with equal potency to the parent peptide, whereas the 5LaaMII analogue showed no inhibitory activity. The active LaaMII analogue was found to exhibit significantly improved permeability across Caco-2 cell monolayers compared to the native MII, and both peptides showed negligible toxicity.

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Cited by 38 publications

References 8 publications

Approaches for enhancing oral bioavailability of peptides and proteins

Approaches for enhancing oral bioavailability of peptides and proteins

Lipid, Sugar and Liposaccharide Based Delivery Systems

Synthesis, Structure Elucidation, in Vitro Biological Activity, Toxicity, and Caco-2 Cell Permeability of Lipophilic Analogues of α-Conotoxin MII

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