scholarly journals Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers

2022 ◽  
pp. 114097
Author(s):  
Soheil Haddadzadegan ◽  
Farid Dorkoosh ◽  
Andreas Bernkop-Schnurch
Keyword(s):  
Oral Delivery ◽  
Therapeutic Peptides

scholarly journals Increased Carrier Peptide Stability through pH Adjustment Improves Insulin and PTH(1-34) Delivery In Vitro and In Vivo Rather than by Enforced Carrier Peptide-Cargo Complexation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 993
Author(s):  
Mie Kristensen ◽  
Ragna Guldsmed Diedrichsen ◽  
Valeria Vetri ◽  
Vito Foderà ◽  
Hanne Mørck Nielsen
Keyword(s):  
Oral Delivery ◽  
Molecular Size ◽  
Therapeutic Peptide ◽  
Enzymatic Stability ◽  
Therapeutic Peptides ◽  
Ph Dependent ◽  
Pharmacologically Active ◽  
High Degree

Oral delivery of therapeutic peptides is hampered by their large molecular size and labile nature, thus limiting their permeation across the intestinal epithelium. Promising approaches to overcome the latter include co-administration with carrier peptides. In this study, the cell-penetrating peptide penetratin was employed to investigate effects of co-administration with insulin and the pharmacologically active part of parathyroid hormone (PTH(1-34)) at pH 5, 6.5, and 7.4 with respect to complexation, enzymatic stability, and transepithelial permeation of the therapeutic peptide in vitro and in vivo. Complex formation between insulin or PTH(1-34) and penetratin was pH-dependent. Micron-sized complexes dominated in the samples prepared at pH-values at which penetratin interacts electrostatically with the therapeutic peptide. The association efficiency was more pronounced between insulin and penetratin than between PTH(1-34) and penetratin. Despite the high degree of complexation, penetratin retained its membrane activity when applied to liposomal structures. The enzymatic stability of penetratin during incubation on polarized Caco-2 cell monolayers was pH-dependent with a prolonged half-live determined at pH 5 when compared to pH 6.5 and 7.4. Also, the penetratin-mediated transepithelial permeation of insulin and PTH(1-34) was increased in vitro and in vivo upon lowering the sample pH from 7.4 or 6.5 to 5. Thus, the formation of penetratin-cargo complexes with several molecular entities is not prerequisite for penetratin-mediated transepithelial permeation a therapeutic peptide. Rather, a sample pH, which improves the penetratin stability, appears to optimize the penetratin-mediated transepithelial permeation of insulin and PTH(1-34).

scholarly journals Multifunctional oral delivery systems for enhanced bioavailability of therapeutic peptides/proteins

2019 ◽  
Vol 9 (5) ◽  
pp. 902-922 ◽  
Author(s):  
Ying Han ◽  
Zhonggao Gao ◽  
Liqing Chen ◽  
Lin Kang ◽  
Wei Huang ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Delivery Systems ◽  
Therapeutic Peptides ◽  
Oral Delivery Systems

scholarly journals Lipid-based nanocarriers for oral delivery of peptides

OCL ◽  
2022 ◽  
Vol 29 ◽  
pp. 1
Author(s):  
Camille Dumont
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Intestinal Transport ◽  
Intestinal Lumen ◽  
Burst Release ◽  
Solid Lipid ◽  
Lipid Nanocarriers ◽  
Therapeutic Peptides ◽  
Poor Stability ◽  
Platelet Shape

Therapeutic peptides can treat a wide variety of diseases with selective and potent action. Their oral bioavailability is strongly limited by an important proteolytic activity in the intestinal lumen and poor permeation across the intestinal border. We have evaluated the capacity of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) to overcome both oral bioavailability limiting aspects, using leuprolide (LEU) as model peptide. Lipidization of LEU by formation of a hydrophobic ion pair (HIP) with sodium docusate enables a significant increase of peptide encapsulation efficiency in both SLN and NLC. The nanocarriers, obtained by high-pressure homogenization, measured 120 nm and were platelet shaped. Regarding the protective effect towards proteolytic degradation, only NLC maintained LEU integrity in presence of trypsin. Intestinal transport, evaluated on Caco-2 (enterocyte-like model) and Caco-2/HT29-MTX (mucin-secreting model) monolayers, showed nanocarriers internalization by enterocytes but no improvement of LEU permeability. Indeed, the combination of nanoparticles platelet-shape with the poor stability of the HIP in the transport medium induces a high burst release of the peptide, limiting nanoparticles capacity to transport LEU across the intestinal border. Stability of peptide lipidization needs to be improved to withstand biorelevant medium to benefit from the advantages of encapsulation in solid lipid nanocarriers and consequently improve their oral bioavailability.

Peptide-enhanced oral delivery of therapeutic peptides and proteins

2013 ◽  
Vol 23 (4) ◽  
pp. 365-373 ◽  
Author(s):  
M. Kristensen ◽  
C. Foged ◽  
J. Berthelsen ◽  
H. Mørck Nielsen
Keyword(s):  
Oral Delivery ◽  
Therapeutic Peptides

scholarly journals Archaeal lipids in oral delivery of therapeutic peptides

2017 ◽  
Vol 108 ◽  
pp. 101-110 ◽  
Author(s):  
Ann-Christin Jacobsen ◽  
Sara M Jensen ◽  
Gert Fricker ◽  
Martin Brandl ◽  
Alexander H. Treusch
Keyword(s):  
Oral Delivery ◽  
Therapeutic Peptides ◽  
Archaeal Lipids

Oral delivery of therapeutic peptides: Barriers and strategies to overcome them

2006 ◽  
Vol 14 (3) ◽  
pp. 107-108
Author(s):  
Andreas Bernkop-Schnürch
Keyword(s):  
Oral Delivery ◽  
Therapeutic Peptides

Oil-Based Formulations for Oral Delivery of Therapeutic Peptides

2000 ◽  
Vol 10 (4) ◽  
pp. 391-407 ◽  
Author(s):  
Christopher J. Kirby
Keyword(s):  
Oral Delivery ◽  
Therapeutic Peptides

scholarly journals An Update on Pharmaceutical Strategies for Oral Delivery of Therapeutic Peptides and Proteins in Adults and Pediatrics

Children ◽  
2020 ◽  
Vol 7 (12) ◽  
pp. 307
Author(s):  
Nirnoy Dan ◽  
Kamalika Samanta ◽  
Hassan Almoazen
Keyword(s):  
Epithelial Cell ◽  
Oral Delivery ◽  
Proteolytic Enzymes ◽  
Therapeutic Drug ◽  
Manufacturing Cost ◽  
Gi Tract ◽  
Mucoadhesive Polymers ◽  
Carrier Molecule ◽  
Therapeutic Peptides ◽  
A Cell

While each route of therapeutic drug delivery has its own advantages and limitations, oral delivery is often favored because it offers convenient painless administration, sustained delivery, prolonged shelf life, and often lower manufacturing cost. Its limitations include mucus and epithelial cell barriers in the gastrointestinal (GI) tract that can block access of larger molecules including Therapeutic protein or peptide-based drugs (TPPs), resulting in reduced bioavailability. This review describes these barriers and discusses different strategies used to modify TPPs to enhance their oral bioavailability and/or to increase their absorption. Some seek to stabilize the TTPs to prevent their degradation by proteolytic enzymes in the GI tract by administering them together with protease inhibitors, while others modify TPPs with mucoadhesive polymers like polyethylene glycol (PEG) to allow them to interact with the mucus layer, thereby delaying their clearance. The further barrier provided by the epithelial cell membrane can be overcome by the addition of a cell-penetrating peptide (CPP) and the use of a carrier molecule such as a liposome, microsphere, or nanosphere to transport the TPP-CPP chimera. Enteric coatings have also been used to help TPPs reach the small intestine. Key efficacious TPP formulations that have been approved for clinical use will be discussed.

Carrier‐Based Systems as Strategies for Oral Delivery of Therapeutic Peptides and Proteins: A Mini‐Review

2021 ◽  
Author(s):  
Mohammad Amin Raeisi Estabragh ◽  
Marzieh Sajadi Bami ◽  
Mandana Ohadi ◽  
Ibrahim M. Banat ◽  
Gholamreza Dehghannoudeh
Keyword(s):  
Oral Delivery ◽  
Therapeutic Peptides

scholarly journals Molecular targeting of FATP4 transporter for oral delivery of therapeutic peptide

2020 ◽  
Vol 6 (14) ◽  
pp. eaba0145 ◽  
Author(s):  
Zhenhua Hu ◽  
Sara Nizzero ◽  
Shreya Goel ◽  
Louis E. Hinkle ◽  
Xiaoyan Wu ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Oral Absorption ◽  
Chitosan Nanoparticles ◽  
Gastric Fluid ◽  
Molecular Targeting ◽  
Murine Models ◽  
Long Chain Fatty Acid ◽  
Poor Patient Compliance ◽  
Therapeutic Peptides ◽  
High Bioavailability

Low oral bioavailability of peptide drugs has limited their application to parenteral administration, which suffers from poor patient compliance. Here, we show that molecular targeting of the FATP4 transporter is an effective approach to specifically transport long-chain fatty acid (LCFA)–conjugated peptides across the enterocytic membrane and, thus, enables oral delivery of drug peptides. We packaged LCFA-conjugated exendin-4 (LCFA-Ex4) into liposomes and coated with chitosan nanoparticles to form an orally deliverable Ex4 (OraEx4). OraEx4 protected LCFA-Ex4 from damage by the gastric fluid and released LCFA-Ex4 in the intestinal cavity, where LCFA-Ex4 was transported across the enterocyte membrane by the FAPT4 transporter. OraEx4 had a high bioavailability of 24.8% with respect to subcutaneous injection and exhibited a substantial hypoglycemic effect in murine models of diabetes mellitus. Thus, molecular targeting of the FATP4 transporter enhances oral absorption of therapeutic peptides and provides a platform for oral peptide drug development.

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