*2.7. Preparation of SEDDS Formulations*

The composition of the utilized SEDDS is depicted in Table 1, as described by Ramakrishnan Venkatasubramanian et al. (data not published, manuscript in preparation).


**Table 1.** Composition of the self-emulsifying drug delivery systems (SEDDS).

The structure of utilized SEDDS excipients is shown in Figure 2. All excipients were weighed in a glass vial and homogenized by stirring with a magnetic bar at 37 ◦C overnight. Two SEDDS were used, each differing in the surface charge: negatively charged Citrem SEDDS and neutral Standard SEDDS. The chosen SEDDS were reported to differ only in the surface charge while maintaining a comparable size suitable for targeting in leaky inflammatory lesions.

Citrem

Standard

DDAB-OND in SEDDS Complex of DDAB and OND

DOTAP-OND in SEDDS Complex of DOTAP and OND

achieved by dissolution of the loaded substance in the SEDDS under stirring with a mag-

utilized throughout the study are summarized in Table 2. The amount of loaded cationic

lipids was equivalent to the amount present in the ion-paired complexes.

**Figure 2.** Chemical structures of SEDDS excipients (the structure of Labrasol was adapted from [36], and the structure of Citrem was adapted from [37]). **Figure 2.** Chemical structures of SEDDS excipients (the structure of Labrasol was adapted from [36], and the structure of Citrem was adapted from [37]).

**Table 1.** Composition of the self-emulsifying drug delivery systems (SEDDS). **SEDDS Captex 300 Labrasol Lipoid S LPC 80 Citrem Maisine CC Peceol (%***w***/***w***) (%***w***/***w***) (%***w***/***w***) (%***w***/***w***) (%***w***/***w***) (%***w***/***w***)**  (negatively charged) 20 40 20 20 - - (neutral) 20 40 20 - 10 10 **Table 2.** The loaded self-emulsifying drug delivery systems (SEDDS). The SEDDS were loaded with the OND complexed with a cationic lipid, the cationic lipid itself or orlistat. The loaded substance was weighted into a vial. Subsequently, the amount of SEDDS was added to reach the required concentration of 100 nmol of a complex per 1 g of SEDDS, 3.8 mg of DDAB or 4.2 mg of DOTAP per 1 g of SEDDS. Orlistat inhibits the activity of gastrointestinal lipases, and in this study, it was used at a concentration of 0.25% (*w*/*w*), prepared as 2.5 mg of orlistat dissolved in 1 g of SEDDS. Loading was achieved by dissolution of the loaded substance in the SEDDS under stirring with a magnetic bar at 37 ◦C overnight. The loaded substances and their respective concentrations utilized throughout the study are summarized in Table 2. The amount of loaded cationic lipids was equivalent to the amount present in the ion-paired complexes.

at the charge ratio 3:1 100 nmol of OND/g SEDDS

at the charge ratio 3:1 100 nmol of OND/g SEDDS

**Name of Formulation Loaded Substance Concentration of Loaded Substance in SEDDS** 


**Table 2.** The loaded self-emulsifying drug delivery systems (SEDDS).

DDAB: dimethyldioctadecylammonium bromide, DOTAP: 1,2-dioleoyl-3-trimethylammonium-propane (chloride salt) and OND: oligonucleotide.
