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Hydrophobic ion pairs (HIPs) of IG are formed using various counterions. HIPs are assessed for log P\n                    <jats:sub>octanol\/water<\/jats:sub>\n                    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\u2010SEDDS in size, stability, and log D\n                    <jats:sub>SEDDS\/release medium<\/jats:sub>\n                    . Oral IG bioavailability in PG\/ZW\u2010SEDDS and PEG\u2010SEDDS is evaluated in rats. Among the various counterions studied, IG\u2010BIS (bis(isotridecyl)sulfosuccinate) HIPs demonstrated the highest log P and an improved dissociation profile. PG\/ZW\u2010SEDDS and PEG\u2010SEDDS have similar \u224840\u00a0nm sizes and are stable over 24 h. Both formulations have log D &gt; 4 in water and &gt;2 in 50\u00a0mM phosphate buffer pH 6.8. PG\/ZW\u2010SEDDS yielded an oral bioavailability of 2.13 \u00b1 0.66% for IG, while the employment of PEG\u2010SEDDS resulted in an oral bioavailability of 1.15 \u00b1 0.35%. This study highlights the prospective utilization of PEG\u2010free SEDDS involving the concurrent application of PG and ZW surfactants, an alternative to conventional PEG surfactants, for improved oral therapeutic (poly) peptide delivery.\n                  <\/jats:p>","DOI":"10.1002\/smll.202307618","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T23:34:37Z","timestamp":1706916877000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Comparative Analysis of PEG\u2010Free and PEG\u2010Based Self\u2010Emulsifying Drug Delivery Systems for Enhanced Oral Bioavailability of Therapeutic (Poly) Peptides"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8979-864X","authenticated-orcid":false,"given":"Soheil","family":"Haddadzadegan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology Institute of Pharmacy University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"To","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology Institute of Pharmacy University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Matteo J\u00f6rgensen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology Institute of Pharmacy University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Wibel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology Institute of Pharmacy University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Laffleur","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology Institute of Pharmacy University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4187-8277","authenticated-orcid":false,"given":"Andreas","family":"Bernkop\u2010Schn\u00fcrch","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology Institute of Pharmacy University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-021-05458-8"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2022.108379"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(03)80156-X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/152091503322527003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14552"},{"key":"e_1_2_8_6_1","first-page":"OE01","volume":"11","author":"Mohanty R. 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