Towards the Application of Supramolecular Self-Associating Amphiphiles as Next-Generation Delivery Vehicles

Abstract

Herein, we present a series of supramolecular self-associating amphiphilic (SSA) salts and establish the potential for these molecular constructs to act as next-generation solution-state molecular delivery vehicles. We characterise the self-association of these SSAs, both alone and when co-formulated with a variety of drug(like) competitive guest species. Single crystal X-ray diffraction studies enable the observation of hydrogen-bonded self-association events in the solid state, whilst high resolution mass spectrometry confirms the presence of anionic SSA dimers in the gas-phase. These same anionic SSA dimeric species are also identified within a competitive organic solvent environment (DMSO-d6/0.5% H2O). However, extended self-associated aggregates are observed to form under aqueous conditions (H2O/5.0% EtOH) in both the absence and presence of these competitive guest species. Finally, through the completion of these studies, we present a framework to support others in the characterisation of such systems.

Supramolecular self-associating amphiphiles (SSAs) as nanoscale enhancers of cisplatin anticancer activity

“…As 1 and 6 were to undergo investigation towards cotreatment applications with cisplatin, a range of physicochemical SSA : cisplatin 1 : 1 co-formulation studies were performed and conrmed that any resultant co-formulated self-associated nanoscale aggregates retained a similar size and stability to those of SSAs previously reported. 7,17 An overview of results obtained from these studies can be found in Table 2. For a detailed discussion of the effects of cisplatin addition to the self-associated aggregates formed with 1 at 298 K in a H 2 O (or D 2 O)/5% ethanol solution, please see our previous work in this area.…”

Supramolecular self-associating amphiphiles (SSAs) as enhancers of antimicrobial agents towards Escherichia coli (E. coli)

“…1). [14][15][16][17][18][19][20][21] Similar constructs developed by Faustino and co-workers have previously been shown to act as amphiphiles with enhanced surfactant properties, attributed to intermolecular hydrogen bonded self-association. 22,23 Additionally, Supuran et al have shown the promise of agents such as SSAs for development as therapeutics against Mycobacterium tuberculosis (TB).…”

“…15,16,25,26 Additionally, not only have we shown SSAs to arrive at the external microbial membrane as self-associated spherical aggregates, 16 but that these aggregates can incorporate small drug(like) guest species. 17 The summation of this evidence has therefore led us to hypothesise that this class of compound has the potential to act as efficacy enhancers for other therapeutic agents. Herein, we characterise the SSA aggregates formed upon the coformulation of 1 (Fig.…”

Di-anionic self-associating supramolecular amphiphiles (SSAs) as antimicrobial agents against MRSA andEscherichia coli

“…21 Furthermore, He and co-workers have developed a complex pillar [5]arene which has been shown to effectively carry, deliver and release the antibiotic vancomycin into methicillin resistant Staphylococcus aureus (MRSA), enhancing the intracellular concentration of the antibiotic and thus enhancing efficacy. 22 Our work in this field to date has led to the identification of a novel class of supramolecular self-associating amphiphiles (SSAs) 23,24 as: selective phospholipid membrane co-ordination agents, 25,26 antimicrobial agents against Gram-negative Escherichia coli (E. coli) and Gram-positive MRSA, [27][28][29] anticancer agents, 30 potential drug delivery vehicles, 31 and therapeutic efficacy enhancement agents. 30,32 Here, we present a series of three next-generation di-anionic SSAs (1, 3, 4 -Fig.…”

“…This is in line with our previous work. 23,24,31 However, as these data are not the main focus of the work presented here, these data are presented within the ESI † only.…”