Development and in vivo evaluation of nanoemulsions for oral delivery of low molecular weight heparin

Zöller, Katrin; Laffleur, Flavia; Claus, Victor; Knoll, Patrick; To, Dennis; Bernkop‐Schnürch, Andreas

doi:10.1016/j.jddst.2023.104686

Cited by 1 publication

(2 citation statements)

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“…Instability of PG/ZW-SEDDS in acidic environment can be attributed to the low pH, where negative charge of polyglyceryl-4 caprate (and) polyglyceryl-6 caprylate can interact with H + therefore limiting droplet stability in acidic pH after 48 h which is in line with previous finding on PG based lipid-based formulations. [62] However, the PEGylation of lipid-based formulations has been demonstrated to confer stability to these formulations within the gastrointestinal (GIT) environment. [63] Our data suggest that acidic environment has a more pronounced impact on PG/ZW-SEDDS compared to PEG-SEDDS.…”

Section: Stability Studiesmentioning

confidence: 99%

“…Surface properties like charge are mainly responsible for the damage of cellular mem-branes, as studies showed higher interactions and damaging effects with cationic surface charges. [62] Besides the quaternary ammonium groups of the zwitterionic PC, also the similar composition of the surface in comparison to cell membranes could be a reason for higher interactions of the phospholipids used in the PG/ZW-SEDDS. In comparison, PEG-SEDDS showed less hemolytic activity in even higher concentrations.…”

Section: Biological Studiesmentioning

confidence: 99%

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Comparative Analysis of PEG‐Free and PEG‐Based Self‐Emulsifying Drug Delivery Systems for Enhanced Oral Bioavailability of Therapeutic (Poly) Peptides

Haddadzadegan,

To,

Matteo Jörgensen

et al. 2024

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This study aims to compare the potential of Polyethylene glycol (PEG‐free and PEG‐based self‐emulsifying drug delivery systems (SEDDS) for the oral administration of insulin glargine (IG). Hydrophobic ion pairs (HIPs) of IG are formed using various counterions. HIPs are assessed for log P octanol/water and dissociation behavior. They are incorporated into SEDDS based on polyglycerol (PG) and zwitterionic surfactant (ZW) using response surface methodology and compared to conventional PEG‐SEDDS in size, stability, and log D SEDDS/release medium. Oral IG bioavailability in PG/ZW‐SEDDS and PEG‐SEDDS is evaluated in rats. Among the various counterions studied, IG‐BIS (bis(isotridecyl)sulfosuccinate) HIPs demonstrated the highest log P and an improved dissociation profile. PG/ZW‐SEDDS and PEG‐SEDDS have similar ≈40 nm sizes and are stable over 24 h. Both formulations have log D > 4 in water and >2 in 50 mM phosphate buffer pH 6.8. PG/ZW‐SEDDS yielded an oral bioavailability of 2.13 ± 0.66% for IG, while the employment of PEG‐SEDDS resulted in an oral bioavailability of 1.15 ± 0.35%. This study highlights the prospective utilization of PEG‐free SEDDS involving the concurrent application of PG and ZW surfactants, an alternative to conventional PEG surfactants, for improved oral therapeutic (poly) peptide delivery.

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Section: Stability Studiesmentioning

confidence: 99%

Section: Biological Studiesmentioning

confidence: 99%