Hydrophobic ion-pairs and lipid-based nanocarrier systems: The perfect match for delivery of BCS class 3 drugs

Phan, Thi Nhu Quynh; Shahzadi, Iram; Bernkop‐Schnürch, Andreas

doi:10.1016/j.jconrel.2019.05.011

Cited by 48 publications

(26 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the twenty years since Meyer and Manning's classic 1998 review, 1 hydrophobic ion pairing (HIP) has gained prominence as a useful strategy for making charged hydrophilic molecules into hydrophobic complexes. The technique has a number of applications and has been used, among others, to dissolve molecules in supercritical CO 2 , 2 dissolve enzymes in organic solvents without losing activity, 3 improve intestinal adsorption [4][5][6] or skin permeation, 7,8 or otherwise enhance bioavailability. 9 This review will focus on one of the most prevalent uses of hydrophobic ion pairing: the complexation and encapsulation of charged hydrophilic small molecule, peptide, or protein therapeutics into drug delivery vehicles.…”

Section: Introduction Overview and Terminologymentioning

confidence: 99%

Hydrophobic ion pairing: encapsulating small molecules, peptides, and proteins into nanocarriers

2019

View full text Add to dashboard Cite

show abstract

Section: Introduction Overview and Terminologymentioning

confidence: 99%

Hydrophobic ion pairing: encapsulating small molecules, peptides, and proteins into nanocarriers

2019

View full text Add to dashboard Cite

show abstract

“…Active pharmaceutical ingredient-ionic liquids (API-ILs) comprise a drug and an appropriate counterion. For the formation of an IL, there are a wide range of cation-anion combinations available and previous studies have shown that different API-ILs can result in improvements in drug solubility, stability, bioavailability, and membrane permeability [1,[19][20][21][22][23]. The flexibility of counterion choice enables selection of an appropriate counterion for specific drug delivery systems.…”

Section: Introductionmentioning

confidence: 99%

Ionic Liquid Forms of the Antimalarial Lumefantrine in Combination with LFCS Type IIIB Lipid-Based Formulations Preferentially Increase Lipid Solubility, In Vitro Solubilization Behavior and In Vivo Exposure

et al. 2019

View full text Add to dashboard Cite

Lipid based formulations (LBFs) are commonly employed to enhance the absorption of highly lipophilic, poorly water-soluble drugs. However, the utility of LBFs can be limited by low drug solubility in the formulation. Isolation of ionizable drugs as low melting, lipophilic salts or ionic liquids (ILs) provides one means to enhance drug solubility in LBFs. However, whether different ILs benefit from formulation in different LBFs is largely unknown. In the current studies, lumefantrine was isolated as a number of different lipophilic salt/ionic liquid forms and performance was assessed after formulation in a range of LBFs. The solubility of lumefantrine in LBF was enhanced 2-to 80-fold by isolation as the lumefantrine docusate IL when compared to lumefantrine free base. The increase in drug loading subsequently enhanced concentrations in the aqueous phase of model intestinal fluids during in vitro dispersion and digestion testing of the LBF. To assess in vivo performance, the systemic exposure of lumefantrine docusate after administration in Type II-MCF, IIIB-MCF, IIIB-LCF, and IV formulations was evaluated after oral administration to rats. In vivo exposure was compared to control lipid and aqueous suspension formulations of lumefantrine free base. Lumefantrine docusate in the Type IIIB-LCF showed significantly higher plasma exposure compared to all other formulations (up to 35-fold higher). The data suggest that isolation of a lipid-soluble IL, coupled with an appropriate formulation, is a viable means to increase drug dose in an oral formulation and to enhance exposure of lumefantrine in vivo.

show abstract

“…Exenatide release from NCs was characterized based on the affinity of HIPs toward the oily phase of NCs and the release medium [25]. A log D of at least 2 has been demanded to keep ≥ 50% of HIPs in NCs [14]. Our results showed that exenatide-THA HIPs with a log D of 2.29 were superior to exenatide-DOC with a log D of 1.2 in SIF.…”

Section: Discussionmentioning

confidence: 84%

“…For the development of NCs, an as low as feasible concentration of PG was used to dissolve HIPs in NCs, as this hydrophilic co-solvent is immediately released from the lipophilic phase in aqueous media promoting the release of HIPs out of the oily droplets [14]. Exenatide release from NCs was characterized based on the affinity of HIPs toward the oily phase of NCs and the release medium [25].…”

Section: Discussionmentioning

confidence: 99%

“…Among the various technologies having been developed to overcome the obstacles limiting oral peptide delivery [9,10], the formation of hydrophobic ion pairs (HIPs) proved to be promising as this can increase the lipophilic character of hydrophilic peptide drugs and thus enhance their permeability of lipophilic membranes [11,12]. Because of a limited stability of HIPs in the GI tract, the incorporation of HIPs into lipophilic carrier systems is advantageous [13][14][15]. In addition to a protective effect towards presystemic metabolism [16][17][18], lipid-based nanocarrier systems in particular proved to be able to facilitate mucus T permeation and to enhance the cellular uptake of peptides [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery

Ismail

Phan

Laffleur

et al. 2020

European Journal of Pharmaceutics and Biopharmaceutics

Self Cite

View full text Add to dashboard Cite

The lipophilic character of peptides can be tremendously improved by hydrophobic ion pairing (HIP) with counterions to be efficiently incorporated into lipid-based nanocarriers (NCs). Herein, HIPs of exenatide with the cationic surfactant tetraheptylammonium bromide (THA) and the anionic surfactant sodium docusate (DOC) were formed to increase its lipophilicity. These HIPs were incorporated into lipid based NCs comprising 41% Capmul MCM, 15% Captex 355, 40% Cremophor RH and 4% propylene glycol. Exenatide-THA NCs showed a log D lipophilic phase (LPh)/release medium (RM) of 2.29 and 1.92, whereas the log D LPh/RM of exenatide-DOC was 1.2 and −0.9 in simulated intestinal fluid and Hanks' balanced salts buffer (HBSS), respectively. No significant hemolytic activity was induced at a concentration of 0.25% (m/v) of both blank and loaded NCs. Exenatide-THA NCs and exenatide-DOC NCs showed a 10-fold and 3-fold enhancement in intestinal apparent membrane permeability compared to free exenatide, respectively. Furthermore, orally administered exenatide-THA and exenatide-DOC NCs in healthy rats resulted in a relative bioavailability of 27.96 ± 5.24% and 16.29 ± 6.63%, respectively, confirming the comparatively higher potential of the cationic surfactant over the anionic surfactant. Findings of this work highlight the potential of the type of counterion used for HIP as key to successful design of lipid-based NCs for oral exenatide delivery.

show abstract

Hydrophobic ion-pairs and lipid-based nanocarrier systems: The perfect match for delivery of BCS class 3 drugs

Cited by 48 publications

References 74 publications

Hydrophobic ion pairing: encapsulating small molecules, peptides, and proteins into nanocarriers

Hydrophobic ion pairing: encapsulating small molecules, peptides, and proteins into nanocarriers

Ionic Liquid Forms of the Antimalarial Lumefantrine in Combination with LFCS Type IIIB Lipid-Based Formulations Preferentially Increase Lipid Solubility, In Vitro Solubilization Behavior and In Vivo Exposure

Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery

Contact Info

Product

Resources

About