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  • Title: Replacing PEG-surfactants in self-emulsifying drug delivery systems: Surfactants with polyhydroxy head groups for advanced cytosolic drug delivery.
    Author: Friedl JD, Jörgensen AM, Nguyen Le NM, Steinbring C, Bernkop-Schnürch A.
    Journal: Int J Pharm; 2022 Apr 25; 618():121633. PubMed ID: 35304244.
    Abstract:
    AIM: Evaluation of different polyhydroxy surfaces in SEDDS to overcome the limitations associated with conventional polyethylene glycol (PEG)-based SEDDS surfaces for intracellular drug delivery. METHODS: Anionic, cationic and non-ionic polyglycerol- (PG-) and alkylpolyglucoside- (APG-) surfactant based SEDDS were developed and compared to conventional PEG-SEDDS. Particular emphasis was placed on the impact of SEDDS surface decoration on size and zeta potential, drug loading and protective effect, mucus diffusion, SEDDS-cell interaction and intracellular delivery of the model drug curcumin. RESULTS: After self-emulsification, SEDDS droplets sizes were within the range of 35-190 nm. SEDDS formulated with high amounts of long PEG-chain surfactants (>10 monomers) a charge-shielding effect was observed. Replacing PEG-surfactants with PG- and an APG-surfactant did not detrimentally affect SEDDS self-emulsification, payloads or the protection of incorporated curcumin towards oxidation. PG- and APG-SEDDS bearing multiple hydroxy functions on the surface demonstrated mucus permeation comparable to PEG-SEDDS. Steric hinderance and charge-shielding of PEG-SEDDS surface substantially reduced cellular uptake up to 50-fold and impeded endosomal escape, yielding in a 20-fold higher association of PEG-SEDDS with lysosomes. In contrast, polyhydroxy-surfaces on SEDDS promoted pronounced cellular internalisation and no lysosomal co-localisation was observed. This improved uptake resulted in an over 3-fold higher inhibition of tumor cell proliferation after cytosolic curcumin delivery. CONCLUSION: The replacement of PEG-surfactants by surfactants with polyhydroxy head groups in SEDDS is a promising approach to overcome the limitations for intracellular drug delivery associated with conventional PEGylated SEDDS surfaces.
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