Oral Protein and Peptide Drug Delivery

Soltero, Rick

doi:10.1002/0471475734.ch10

Cited by 10 publications

(5 citation statements)

References 49 publications

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“…Oral administration is the most convenient and favorable route for delivering drugs; nevertheless, it has proven to be extremely challenging for peptides and proteins. 15 In an attempt to overcome the shortcomings associated with oral bioavailability of peptides, a diverse array of chemical modifications have been explored including esterification, 16 amidation 17 (dermorphin analogues), and cyclization (αconotoxin Vc1.1). 18 A well-studied approach to produce systemically active peptide analogues is conjugation to saccharide units.…”

Section: ■ Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of an Orally Active Glycosylated Endomorphin-1

et al. 2012

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The endogenous opioid peptide endomorphin-1 (1) was modified by attachment of lactose to the N-terminus via a succinamic acid spacer to produce compound 2. The carbohydrate modification significantly improved the metabolic stability and membrane permeability of 2 while retaining μ-opioid receptor binding affinity and agonist activity. Analogue 2 produced dose-dependent antinociceptive activity following intravenous administration in a chronic constriction injury (CCI) rat model of neuropathic pain with an ED(50) of 8.3 (± 0.8) μmol/kg. The corresponding ED(50) for morphine was 2.6 (± 1.4) μmol/kg. Importantly, compound 2 produced dose-dependent pain relief after oral administration in CCI rats (ED(50) = 19.6 (± 1.2) μmol/kg), which was comparable with that of morphine (ED(50) = 20.7 (±3.6) μmol/kg). Antineuropathic effects of analogue 2 were significantly attenuated by pretreatment of animals with the opioid antagonist naloxone, confirming opioid receptor-mediated analgesia. In contrast to morphine, no significant constipation was produced by compound 2 after oral administration.

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Section: ■ Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of an Orally Active Glycosylated Endomorphin-1

et al. 2012

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“…The stability of insulin has been evaluated in the presence of excipients that inhibit these enzymes. Representative inhibitors of trypsin and α-chymotrypsin include pancreatic inhibitor and soybean trypsin inhibitor, FK-448, Camostatmesylate and aprotinin 16 .Thiomers are promising candidates as enzyme inhibitors in strong reduction of albumin degradation by a mixture of proteases in the presence of carbopol 934P 17 . A subsequent study showed that polycarbophil and carbopol 934P were potent inhibitors of the proteolytic enzymes trypsin, α-chymotrypsin and carboxypeptidase A.…”

Section: Enzyme Inhibitors (Protease) 14mentioning

confidence: 99%

Protein and Peptide Based Drug Delivery- A Review

Kamala¹,

Yamini²,

Srinivasa³

et al. 2022

Int J Life Sci Pharm Res

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Biologics include vaccines, recombinant proteins, genes, synthetic tissues and viruses, which have emerged from molecular and cellular biology, with respect to unmet clinical needs and expanding indications. Hence it is important at this stage to outline the essential events that have led to the current level of interest in protein and peptide drug delivery systems. Polymers consisting of amino acids that are covalently linked by peptide bonds are known as Proteins and inturn peptides are small proteins composed of few dozen amino acids. Due to large molecular sizes of the proteins ranging from thousands to several millions atomic masses sizes; absorption through the epithelial barriers in the gastrointestinal tract is low. Moreover, proteins are rapidly degraded by digestive enzymes. As the bioavailability by oral route is poor they can be administered by other routes mainly by parenteral (IV, SC, IM) injections. The biological activity of proteins is strongly dependent on their molecular structure i.e 10 structure; the amino acid sequence, which ultimately dictates the non-covalent interactions and the 20i.e alpha helices and beta helices; the periodic spatial arrangement of the polypeptide chain backbone and 30; the 3-dimensional conformation of the whole molecule, including the positions of all amino acid side chains. Some proteins may consist of multiple peptide chains grouped together by non-covalent intermolecular interactions. The arrangement of these subunits relative to each other constitutes the 40structure. An alteration at any level of molecular structure leads to a change or loss of biological activity. The present review focuses on the development of various routes of drug administration, formulation as well as stability aspects of protein and peptide drug delivery system.

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“…In addition, the BBB is not the only physiological barrier for drug delivery to the brain. If we consider the anatomic aspects of our body, the brain and the spinal cord are completely cushioned and protected by the cerebrospinal fluid (CSF) [42,43]. This fluid is also responsible for carrying nutrients to and waste products away from the brain.…”

Section: Other Barriers That Limit Effective Drug Delivery Into the Bmentioning

confidence: 99%

“…NPs can also be loaded with therapeutic molecules that are released in a controlled way and, at the same time, retain the drug stability and prevent them from degradation once in the blood. Therefore, for an efficient drug delivery into the CNS, it is very important to engineer NPs with the following properties: (i) small size (NP diameter should be smaller than 100 nm); (ii) biocompatible, biodegradable, nontoxic and noninflammatory; (iii) prolonged circulation time in the body; (iv) stable in the plasma; (v) protect the cargo such as small molecules, peptides [43,[49][50][51], proteins or nucleic acids from degradation; (vi) targetability to the BBB and (vii) controlled drug release [44].…”

Section: Nps For Brain Drug Deliverymentioning

confidence: 99%

Multifunctional Nanoparticles for Successful Targeted Drug Delivery across the Blood-Brain Barrier

Vieira¹,

Gamarra²

2018

Molecular Insight of Drug Design

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The blood-brain barrier (BBB) is the major problem for the treatment of brain diseases because we need to be able to deliver drugs from the vascular system into the central nervous system (CNS). There are no drug therapies for a wide range of CNS diseases and these include neurodegenerative diseases such as Alzheimer's and Parkinson's diseases and cerebral ischemia. Therefore, the focus of this chapter is to discuss how nanoparticles (NPs) can be modified to transport different drug molecules for the treatment of brain diseases. In essence, NPs' surface can be functionalized with molecules such as peptides, antibodies and RNA aptamers and these macromolecules can be attached to the receptors present at the BBB endothelial cell surface, which allows the NPs cross the barrier and subsequently deliver pharmaceuticals to the brain for the therapeutic and/or imaging of neurological disorders. In fact, part of the difficulty in finding an effective treatment for these CNS disorders is that there is not yet an efficient delivery method for drug delivery across the BBB. However, over the last several years, researches have started to understand some of the design rules to efficiently deliver NPs to the brain.

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Oral Protein and Peptide Drug Delivery

Cited by 10 publications

References 49 publications

Synthesis and Biological Evaluation of an Orally Active Glycosylated Endomorphin-1

Synthesis and Biological Evaluation of an Orally Active Glycosylated Endomorphin-1

Protein and Peptide Based Drug Delivery- A Review

Multifunctional Nanoparticles for Successful Targeted Drug Delivery across the Blood-Brain Barrier

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