Cyclodextrins in peptide and protein delivery

Irie, Tetsumi

doi:10.1016/s0169-409x(98)00057-x

Cited by 271 publications

(126 citation statements)

References 125 publications

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“…Enzymatic degradation affects both the fraction absorbed and also the half lives of peptides in the body. 7 The cleavage of peptide bond occurs either at the amino or carboxyl terminus of the chain by exopeptidases (i.e. aminopeptidase and carboxypeptidase).…”

Section: Drawbacks Associated With Proteins and Peptidesmentioning

confidence: 99%

“…Also, they have a molecular size >500 Da which restricts its paracellular transport through the tight junctions. 7 Hence, their delivery through oral route becomes difficult. The contact time with the absorbing surface for the delivery system of proteins and peptides are too short to allow therapeutic level to be maintained for a long period of time.…”

Section: Drawbacks Associated With Proteins and Peptidesmentioning

confidence: 99%

“…In contrast, the internal cavity is lined with ether oxygen at 4 th position and hydrogens at 3 rd , 5 th and 6 th position. Various effects of cyclodextrins on different proteins are: protection against degradation (if point of attack of a protease is sterically `masked' by cyclodextrin), aggregation suppression (if residues responsible for aggregation are highly solvent accessible), alteration of function (if residues involved in function are `masked' by cyclodextrin) 7 .…”

Section: Complexation With Cyclodextrinsmentioning

confidence: 99%

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Structural Modification of Proteins and Peptides

Rawat¹,

Bhatt²,

Chauhan³

2014

IJPER

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Proteins and peptides are ubiquitous in every cell and thus are vital for various biological functions. In recent years, there is an extensive growth in the development of various biologicals and large molecules like proteins and peptides. Now, they are replacing the market of existing organic based pharmaceuticals. This review article intends to summarize various structural modifications that are carried out in order to alter basic properties of peptides and proteins so that their solubility, absorption, permeability and various other problems associated with their delivery can be resolved. Thus they can offer significant therapeutic potential.

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Section: Drawbacks Associated With Proteins and Peptidesmentioning

confidence: 99%

Section: Drawbacks Associated With Proteins and Peptidesmentioning

confidence: 99%

Section: Complexation With Cyclodextrinsmentioning

confidence: 99%

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Structural Modification of Proteins and Peptides

Rawat¹,

Bhatt²,

Chauhan³

2014

IJPER

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“…CDs are known as cytotoxic elements because of their binding to membrane cholesterol and proceeding by hemolysis, but they are safe in oral administration because of their poor absorption from the GI tract (28,(31)(32)(33).…”

Section: Introductionmentioning

confidence: 99%

Development of Acid-Resistant Alginate/Trimethyl Chitosan Nanoparticles Containing Cationic β-Cyclodextrin Polymers for Insulin Oral Delivery

et al. 2015

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Abstract. In this study, the use of trimethylchitosan (TMC), by higher solubility in comparison with chitosan, in alginate/chitosan nanoparticles containing cationic β-cyclodextrin polymers (CPβCDs) has been studied, with the aim of increasing insulin uptake by nanoparticles. Firstly, TMCs were synthesized by iodomethane, and CPβCDs were synthesized within a one-step polycondensation reaction using choline chloride (CC) and epichlorohydrine (EP). Insulin-CβCDPs complex was prepared by mixing 1:1 portion of insulin and CPβCDs solutions. Then, nanoparticles prepared in a three-step procedure based on the iono-tropic pregelation method. Nanoparticles screened using experimental design and Placket Burman methodology to obtain minimum size and polydispercity index (pdI) and the highest entrapment efficiency (EE). CPβCDs and TMC solution concentration and pH and alginate and calcium chloride solution concentrations are found as the significant parameters on size, PdI, and EE. The nanoparticles with proper physicochemical properties were obtained; the size, PdI, and EE% of optimized nanoparticles were reported as 150.82±21 nm, 0.362±0.036, and 93.2%±4.1, respectively. The cumulative insulin release in intestinal condition achieved was 50.2% during 6 h. By SEM imaging, separate, spherical, and nonaggregated nanoparticles were found. In the cytotoxicity studies on Caco-2 cell culture, no significant cytotoxicity was observed in 5 h of incubation, but after 24 h of incubation, viability was decreased to 50% in 0.5 mμ of TMC concentration. Permeability studies across Caco-2 cells had been carried out, and permeability achieved in 240 min was 8.41±0.39%, which shows noticeable increase in comparison with chitosan nanoparticles. Thus, according to the results, the optimized nanoparticles can be used as a new insulin oral delivery system.

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“…[16][17][18][19][20][21] In their hydrophobic cavity a wide range of compounds ranging from ions to proteins [22][23][24][25] can be trapped. In addition, CDs exhibit low toxicity and low immunogenicity, 26 and they have been used in the pharmaceutical field by promoting CD-drug complexes in order to improve the absorption, distribution, metabolism, excretion, and toxicity (ADMET)-related properties of a drug (eg, solubility, stability, delivery and release, membrane permeability and absorption, toxicity).…”

mentioning

confidence: 99%

Rescuing compound bioactivity in a secondary cell-based screening by using γ-cyclodextrin as a molecular carrier

Clavería-Gimeno¹,

Vega²,

Grazú³

et al. 2015

IJN

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In vitro primary screening for identifying bioactive compounds (inhibitors, activators or pharmacological chaperones) against a protein target results in the discovery of lead compounds that must be tested in cell-based efficacy secondary screenings. Very often lead compounds do not succeed because of an apparent low potency in cell assays, despite an excellent performance in primary screening. Primary and secondary screenings differ significantly according to the conditions and challenges the compounds must overcome in order to interact with their intended target. Cellular internalization and intracellular metabolism are some of the difficulties the compounds must confront and different strategies can be envisaged for minimizing that problem. Using a novel screening procedure we have identified 15 compounds inhibiting the hepatitis C NS3 protease in an allosteric fashion. After characterizing biophysically the interaction with the target, some of the compounds were not able to inhibit viral replication in cell assays. In order to overcome this obstacle and potentially improve cellular internalization three of these compounds were complexed with γ-cyclodextrin. Two of them showed a five- and 16-fold activity increase, compared to their activity when delivered as free compounds in solution (while γ-cyclodextrin did not show antiviral activity by itself). The most remarkable result came from a third compound that showed no antiviral activity in cell assays when delivered free in solution, but its γ-cyclodextrin complex exhibited a 50% effective concentration of 5 μM. Thus, the antiviral activity of these compounds can be significantly improved, even completely rescued, using γ-cyclodextrin as carrier molecule.

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Cyclodextrins in peptide and protein delivery

Cited by 271 publications

References 125 publications

Structural Modification of Proteins and Peptides

Structural Modification of Proteins and Peptides

Development of Acid-Resistant Alginate/Trimethyl Chitosan Nanoparticles Containing Cationic β-Cyclodextrin Polymers for Insulin Oral Delivery

Rescuing compound bioactivity in a secondary cell-based screening by using γ-cyclodextrin as a molecular carrier

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Cyclodextrins in peptide and protein delivery

Cited by 271 publications

References 125 publications

Structural Modification of Proteins and Peptides

Structural Modification of Proteins and Peptides

Development of Acid-Resistant Alginate/Trimethyl Chitosan Nanoparticles Containing Cationic β-Cyclodextrin Polymers for Insulin Oral Delivery

Rescuing compound bioactivity in a secondary cell-based screening by using&nbsp;&gamma;-cyclodextrin as&nbsp;a molecular carrier

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Rescuing compound bioactivity in a secondary cell-based screening by using γ-cyclodextrin as a molecular carrier