Development of a SMEDDS for oral delivery of hydrophilic peptide difelikefalin acetate: Preparation, characterization, and PK/PD evaluation.

Ming C, Li Z, Zhou W

Journal of pharmaceutical sciences6 Jun 2026

PMID42250802DOI10.1016/j.xphs.2026.104356PepBankPUB-42250802

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study12

1 result from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Pharmacokinetics
In rats, oral difelikefalin solution had bioavailability of 0.656% relative to intravenous administration.
In plain wordsIn rats, oral difelikefalin solution had low bioavailability relative to intravenous administration.
Peptide
Difelikefalin
Outcome
Not applicableOral solution bioavailability
Study
ratn: not reported in source
Comparator
Intravenous administration
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated · oralAs given in this study (rat).
Measurements
Oral bioavailability
0.656%
solution
Source sentences
Summary
The rat pharmacokinetic study showed that, relative to intravenous administration, the oral bioavailability of the DF solution was 0.656%, whereas that of DF self-microemulsifying drug delivery systems (SMEDDS) was 2.04%, representing a 3-fold increase.
Report a problemFND-4225080210

Studies that did not test the peptide alone11

In this study, Difelikefalin was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Difelikefalin.

02AnimalNot a test of Difelikefalin aloneAnimal study (in vivo)Pharmacokinetics
In rats, oral difelikefalin SMEDDS had bioavailability of 2.04%, a 3-fold increase over the solution.
In plain wordsIn rats, oral difelikefalin SMEDDS increased bioavailability compared with the oral solution.
Peptide
Difelikefalin
Outcome
IncreaseOral SMEDDS bioavailability
Study
ratn: not reported in source
Comparator
Oral difelikefalin solution
Outcome group
Pharmacokinetics · Pharmacology
Measurements
Oral bioavailability
2.04%
SMEDDS
Increase
3 fold
versus solution
Source sentences
Summary
The rat pharmacokinetic study showed that, relative to intravenous administration, the oral bioavailability of the DF solution was 0.656%, whereas that of DF self-microemulsifying drug delivery systems (SMEDDS) was 2.04%, representing a 3-fold increase.
In this study, Difelikefalin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Difelikefalin.
Report a problemFND-4225080211
03AnimalNot a test of Difelikefalin aloneAnimal study (in vivo)Efficacy outcome
In mice, oral difelikefalin SMEDDS at 5 mg/kg inhibited scratching comparably to difelikefalin injection at 0.3 mg/kg.
In plain wordsIn mice, oral difelikefalin SMEDDS inhibited scratching comparably to injected difelikefalin.
Peptide
Difelikefalin
Outcome
Direction not reportedScratching episode inhibition
Study
mousen: not reported in source
Comparator
Difelikefalin injection 0.3 mg/kg
Outcome group
Skin and hair · Skin and wound
Source sentences
Summary
In the mouse pharmacodynamic test, the scratching episodes inhibition of orally administered DF SMEDDS at a dose of 5 mg/kg was comparable to that of DF injection at 0.3 mg/kg.
In this study, Difelikefalin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Difelikefalin.
Report a problemFND-4225080212
04LabNot a test of Difelikefalin aloneIn vitro (cell-free)Activity measurement
In laboratory formulation tests, difelikefalin concentrate formed droplets measuring 53-59 nm across the tested media.
In plain wordsIn lab tests, difelikefalin concentrate formed small droplets in the tested liquids.
Peptide
Difelikefalin
Outcome
Not applicableSMEDDS droplet size
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Measurements
Droplet size
53 to 59 nm
reported result
Source sentences
Summary
The concentrate can achieve self-emulsification in purified water, pH 1.2(HCl solution), pH 4.5(acetate buffer), and pH 6.8(phosphate buffer) media, with a droplet size of 53-59 nm, polydispersity index (PDI) of 0.09-0.27, zeta potential of -36.39 to -6.1 mV, and drug loading of 90.3%.
In this study, Difelikefalin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Difelikefalin.
Report a problemFND-4225080201
05LabNot a test of Difelikefalin aloneIn vitro (cell-free)Activity measurement
In laboratory formulation tests, difelikefalin concentrate had a polydispersity index of 0.09-0.27.
In plain wordsIn lab tests, difelikefalin concentrate had the reported range of droplet size variation.
Peptide
Difelikefalin
Outcome
Not applicableSMEDDS polydispersity index
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Measurements
PDI
0.09 to 0.27
reported result
Source sentences
Summary
The concentrate can achieve self-emulsification in purified water, pH 1.2(HCl solution), pH 4.5(acetate buffer), and pH 6.8(phosphate buffer) media, with a droplet size of 53-59 nm, polydispersity index (PDI) of 0.09-0.27, zeta potential of -36.39 to -6.1 mV, and drug loading of 90.3%.
In this study, Difelikefalin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Difelikefalin.
Report a problemFND-4225080202
06LabNot a test of Difelikefalin aloneIn vitro (cell-free)Activity measurement
In laboratory formulation tests, difelikefalin concentrate had a zeta potential of -36.39 to -6.1 mV.
In plain wordsIn lab tests, difelikefalin concentrate had a negative zeta potential.
Peptide
Difelikefalin
Outcome
Not applicableSMEDDS zeta potential
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Measurements
Zeta potential
−36.39 to −6.1 mV
reported result
Source sentences
Summary
The concentrate can achieve self-emulsification in purified water, pH 1.2(HCl solution), pH 4.5(acetate buffer), and pH 6.8(phosphate buffer) media, with a droplet size of 53-59 nm, polydispersity index (PDI) of 0.09-0.27, zeta potential of -36.39 to -6.1 mV, and drug loading of 90.3%.
In this study, Difelikefalin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Difelikefalin.
Report a problemFND-4225080203
07LabNot a test of Difelikefalin aloneIn vitro (cell-free)Activity measurement
In laboratory formulation tests, difelikefalin concentrate achieved drug loading of 90.3%.
In plain wordsIn lab tests, difelikefalin concentrate achieved the reported drug loading.
Peptide
Difelikefalin
Outcome
Not applicableDrug loading
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Measurements
Drug loading
90.3%
reported result
Source sentences
Summary
The concentrate can achieve self-emulsification in purified water, pH 1.2(HCl solution), pH 4.5(acetate buffer), and pH 6.8(phosphate buffer) media, with a droplet size of 53-59 nm, polydispersity index (PDI) of 0.09-0.27, zeta potential of -36.39 to -6.1 mV, and drug loading of 90.3%.
In this study, Difelikefalin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Difelikefalin.
Report a problemFND-4225080204
08LabNot a test of Difelikefalin aloneIn vitro (cell-free)Activity measurement
In laboratory release tests at pH 6.8, difelikefalin solution released almost completely at 8 h.
In plain wordsIn lab tests, difelikefalin solution released almost completely within the reported period.
Peptide
Difelikefalin
Outcome
Not applicableSolution release
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
In vitro release results showed that the DF solution was almost completely released at 8 h in pH 6.8 medium, while the DF self-microemulsion only achieved approximately 20% release at 24 h.
In this study, Difelikefalin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Difelikefalin.
Report a problemFND-4225080205
09LabNot a test of Difelikefalin aloneIn vitro (cell-free)Activity measurement
In laboratory release tests, difelikefalin self-microemulsion achieved approximately 20% release at 24 h.
In plain wordsIn lab tests, difelikefalin self-microemulsion released slowly.
Peptide
Difelikefalin
Outcome
Not applicableSelf-microemulsion release
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Measurements
Release
≈ 20%
24 h
Source sentences
Summary
In vitro release results showed that the DF solution was almost completely released at 8 h in pH 6.8 medium, while the DF self-microemulsion only achieved approximately 20% release at 24 h.
In this study, Difelikefalin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Difelikefalin.
Report a problemFND-4225080206
10LabNot a test of Difelikefalin aloneIn vitro (cell-free)Activity measurement
In laboratory enzyme tests, trypsin could not effectively degrade difelikefalin.
In plain wordsIn lab tests, trypsin did not effectively break down difelikefalin.
Peptide
Difelikefalin
Outcome
Not applicableTrypsin degradation
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
Enzymatic degradation experiments demonstrated that trypsin, elastase, and α-chymotrypsin could not effectively degrade DF.
In this study, Difelikefalin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Difelikefalin.
Report a problemFND-4225080207
11LabNot a test of Difelikefalin aloneIn vitro (cell-free)Activity measurement
In laboratory enzyme tests, elastase could not effectively degrade difelikefalin.
In plain wordsIn lab tests, elastase did not effectively break down difelikefalin.
Peptide
Difelikefalin
Outcome
Not applicableElastase degradation
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
Enzymatic degradation experiments demonstrated that trypsin, elastase, and α-chymotrypsin could not effectively degrade DF.
In this study, Difelikefalin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Difelikefalin.
Report a problemFND-4225080208
12LabNot a test of Difelikefalin aloneIn vitro (cell-free)Activity measurement
In laboratory enzyme tests, α-chymotrypsin could not effectively degrade difelikefalin.
In plain wordsIn lab tests, alpha-chymotrypsin did not effectively break down difelikefalin.
Peptide
Difelikefalin
Outcome
Not applicableAlpha-chymotrypsin degradation
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
Enzymatic degradation experiments demonstrated that trypsin, elastase, and α-chymotrypsin could not effectively degrade DF.
In this study, Difelikefalin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Difelikefalin.
Report a problemFND-4225080209

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:35 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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