Self-assembled sorbitol-derived supramolecular hydrogels for the controlled encapsulation and release of active pharmaceutical ingredients

Howe, Edward J.; Okesola, Babatunde O.; Smith, David K.

doi:10.1039/c5cc01868d

Cited by 61 publications

(41 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Examples are cell division and motility which are regulated by dynamic assembly of microtubules and actin filaments, respectively. [6][7][8] Some small synthetic molecules also undergo supramolecular polymerization to yield hydrogels that assemble and disassemble in response to external stimuli, 9,10 and are being developed for applications in controlled drug delivery 11,12 and tissue engineering. [13][14][15] Synthetic supramolecular polymers are also being exploited in nanofabrication, for the development of nanowires [16][17][18][19] or as components of artificial molecular machines.…”

Section: Introductionmentioning

confidence: 99%

Modulation of the cooperativity in the assembly of multistranded supramolecular polymers

Campanella

Lopez-Fontal

Milanesi

et al. 2017

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

It is highly desirable that supramolecular polymers self-assemble following small changes in the environment. The degree of responsiveness depends on the degree of cooperativity at play during the assembly. Undertanding how to modulate and quantify cooperativity is therefore highly desirable for the study and design of responsive polymers. Here we show that the cooperative assembly of a porphyrin-based, double-stranded polymer is triggered by changes in building blocks and in salt concentration. We develop a model that accounts for this responsiveness by assuming the binding of the salt countercations to the double-stranded polymer. Using our assembly model we generate plots that show the increase in concentration of polymer versus the normalized concentration of monomer. These plots are ideally suited to appreciate changes in cooperativity, and show that, for our system, these changes are consistent with the increase in polymer length observed experimentally. Unexpectedly, we find that polymer stability increases when cooperativity decreases. We attribute this behaviour to the fact that increasing salt concentration stabilizes the overall polymer more than the nucleus. In other words, the cooperativity factor , defined as the ratio between the growth constant Kg and the nucleation constant Kn decreases as the overall stability of the polymer increases. Using our model to simulate the data, we generate cooperativity plots to explore changes in cooperativity for multistranded polymers. We find that, for the same pairwise association constants, the cooperativity sharply increases with the number of strands in the polymer. We attribute this dependence to the fact that the larger the number of strands, the larger is the nucleus necessary to trigger polymer growth. We show therefore that the cooperativty factor  does not properly account for the cooperativity behaviour of multistranded polymers, or any supramolecular polymer with a nucleus composed of more than 2 building blocks, and propose the use of the corrected cooperativity factor m. Finally, we show that multistranded polymers display highly cooperative polymerisation with pairwise association constants as low as 10 M -1 between the building blocks, which should simplify the design of responsive supramolecular polymers.

show abstract

Section: Introductionmentioning

confidence: 99%

Modulation of the cooperativity in the assembly of multistranded supramolecular polymers

Campanella

Lopez-Fontal

Milanesi

et al. 2017

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

show abstract

“…A supramolecular hydrogelator ( G48 ) derived from sorbitol for encapsulation and release of various drugs was investigated by Smith and co‐workers . The hydrogel of G48 was found to encapsulate an anti‐inflammatory drug namely mesalazine ( MSZ ) in acetate buffer (pH 4.65); the drug loading capacity of G48 was 1 molar equivalent indicating 1:1 G48:MSZ interactions within the hydrogel.…”

Section: Designing Lmwgsmentioning

confidence: 99%

“…a) Structure of gelator G48 and the anti‐inflammatory drugs ( MSZ , NPX, and IBU ); b) release profiles of NPX from G48 hydrogel into a supernatant aqueous solution under different conditions of pH control. Reproduced with permission . Copyright 2015, Royal Society of Chemistry.…”

Section: Designing Lmwgsmentioning

confidence: 99%

Supramolecular Synthon Approach in Designing Molecular Gels for Advanced Therapeutics

Dastidar

Roy

Parveen

2018

Advanced Therapeutics

View full text Add to dashboard Cite

Low‐molecular‐weight gelators (LMWGs) are an important class of soft materials that offer various potential applications including drug delivery. Structural diversities of the reported LMWGs and lack of molecular‐level understanding of the self‐assembly process of gelation make it difficult to design a gelator a priori. Most often gelators are discovered in a serendipitous manner and second‐generation gelators are designed by modifying known gelling scaffolds. Since gel network within which the solvent molecules are immobilized is often found to be crystalline, a supramolecular synthon approach in the context of crystal engineering is demonstrated to be quite effective in designing LMWGs for various applications including therapeutics. Self‐drug‐delivery systems, wherein the need for a delivery vehicle does not exist, are becoming an effective alternative to conventional drug delivery systems. In the form of a simple gel (for non‐invasive topical application) or injectable gel (for invasive subcutaneous applications), LMWGs derived from drugs provide an effective way to develop self‐drug‐delivery systems. This review article encompasses the early development of LMWG research, describes gradual transition from discovering just a gelator to a gelator having potential material applications including drug delivery, and highlights the merit of supramolecular synthon approach in designing LMWGs for self‐drug‐delivery applications.

show abstract

“…[1][2][3][4][5] These types of viscoelastic materials are becoming more popular,m ainly because of their variousp otentiala pplications in electro-optics/photonics, [6,7] sensors, [8][9][10] cosmetics, [11] structuredirectinga gents, [12] conservation of art, [13] catalysis, [14] biomedical applications, [15][16][17][18][19][20] biomaterials, [21][22][23][24][25][26][27][28] and so forth. [1][2][3][4][5] These types of viscoelastic materials are becoming more popular,m ainly because of their variousp otentiala pplications in electro-optics/photonics, [6,7] sensors, [8][9][10] cosmetics, [11] structuredirectinga gents, [12] conservation of art, [13] catalysis, [14] biomedical applications, [15][16][17][18][19]…”

Section: Introductionmentioning

confidence: 99%

“…Supramolecular gels are an important class of soft materiald erived from low-molecular-weight gelators (LMWGs;u sually small molecules with molecular weights of less than 3000). [1][2][3][4][5] These types of viscoelastic materials are becoming more popular,m ainly because of their variousp otentiala pplications in electro-optics/photonics, [6,7] sensors, [8][9][10] cosmetics, [11] structuredirectinga gents, [12] conservation of art, [13] catalysis, [14] biomedical applications, [15][16][17][18][19][20] biomaterials, [21][22][23][24][25][26][27][28] and so forth. Although there are literarily hundreds of LMWGs reported, designing them is af ormidable task because exact molecular-level information about gelation is still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Rationally Developed Organic Salts of Tolfenamic Acid and Its β‐Alanine Derivatives for Dual Purposes as an Anti‐Inflammatory Topical Gel and Anticancer Agent

Parveen

Sravanthi

Dastidar

2017

Chemistry An Asian Journal

View full text Add to dashboard Cite

A new series of primary ammonium monocarboxylate (PAM) salts of a nonsteroidal anti-inflammatory drug (NSAID), namely, tolfenamic acid (TA), and its β-alanine derivatives were generated. Nearly 67 % of the salts in the series showed gelling abilities with various solvents, including water (biogenic solvent) and methyl salicylate (typically used for topical gel formulations). Gels were characterized by rheology, electron microscopy, and so forth. Structure-property correlations based on single-crystal and powder XRD data of several gelator and nongelator salts revealed intriguing insights. Studies (in vitro) on an aggressive human breast cancer cell line (MDA-MB-231) with the l-tyrosine methyl ester salt of TA (S7) revealed that the hydrogelator salt was more effective at killing cancer cells than the mother drug TA (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay); displayed better anti-inflammatory activity compared with that of TA (prostaglandin E assay); could be internalized within the cancer cells, as revealed by fluorescence microscopy; and inhibited effectively migration of the cancer cells. Thus, the easily accessible ambidextrous gelator salt S7 can be used for two purposes: as an anti-inflammatory topical gel and as an anticancer agent.

show abstract

Self-assembled sorbitol-derived supramolecular hydrogels for the controlled encapsulation and release of active pharmaceutical ingredients

Abstract: /0000-0002-9881-2714 (2015) Self-assembled sorbitol-derived supramolecular hydrogels for the controlled encapsulation and release of active pharmaceutical ingredients. Chemical Communications. pp. 7451-7454.

Cited by 61 publications

References 44 publications

Modulation of the cooperativity in the assembly of multistranded supramolecular polymers

Modulation of the cooperativity in the assembly of multistranded supramolecular polymers

Supramolecular Synthon Approach in Designing Molecular Gels for Advanced Therapeutics

Rationally Developed Organic Salts of Tolfenamic Acid and Its β‐Alanine Derivatives for Dual Purposes as an Anti‐Inflammatory Topical Gel and Anticancer Agent

Contact Info

Product

Resources

About