Spatially-resolved soft materials for controlled release – hybrid hydrogels combining a robust photo-activated polymer gel with an interactive supramolecular gel

Hybrid hydrogels based on self-assembling low-molecular-weight gelator (LMWG) DBS-CONHNH2 (DBS = 1,3;2,4-dibenzylidene-D-sorbitol) and crosslinked polymer gelator (PG) PEGDM (poly(ethyleneglycol) dimethacrylate) are reported, and an active pharmaceutical ingredient (naproxen, NPX) is incorporated. The use of PEGDM as PG enhances the mechanical stiffness of the hybrid gel (G′ increases from 400 to 4500 Pa) – the LMWG enhances its stability to very high frequency. Use of DBS-CONHNH2 as LMWG enables interactions with NPX and hence allows pH-mediated NPX release – the PG network is largely orthogonal and only interferes to a limited extent. Use of photo-activated PEGDM as PG enables spatially-resolved photo-patterning of robust hybrid gel domains within a preformed LMWG network – the presence of the LMWG enhances the spatial resolution. The photo-patterned multi-domain gel retains pH-mediated NPX release properties and directionally releases NPX into a compartment of higher pH. The two components within these hybrid PG/LMWG hydrogels therefore act largely independently of one another, although they do modify each others properties in subtle ways. Hybrid hydrogels capable of spatially controlled unidirectional release have potential applications in tissue engineering and drug-delivery

Safe approaches for camptothecin delivery: Structural analogues and nanomedicines

[EN] Twenty-(S)-camptothecin is a strongly cytotoxic molecule with excellent antitumor activity over a wide spectrum of human cancers. However, the direct formulation is limited by its poor water solubility, low plasmatic stability and severe toxicity, which currently limits its clinical use. As a consequence, two strategies have been developed in order to achieve safe and efficient delivery of camptothecin to target cells: structural analogues and nanomedicines. In this review, we summarize recent advances in the design, synthesis and development of camptothecin molecular derivatives and supramolecular vehicles, following a systematic classification according to structure-activity relationships (structural analogues) or chemical nature (nanomedicines). A series of organic, inorganic and hybrid materials are presented as nanoplatforms to overcome camptothecin restrictions in administration, biodistribution, pharmacokinetics and toxicity. Nanocarriers which respond to a variety of stimuli endogenously (e.g., pH, redox potential, enzyme activity) or exogenously (e.g., magnetic field, light, temperature, ultrasound) seem the best positioned therapeutic materials for optimal spatial and temporal control over drug release. The main goal of this review is to be used as a source of relevant literature for others interested in the field of camptothecin-based therapeutics. To this end, final remarks on the most important formulations currently under clinical trial are provided. (C) 2016 Elsevier B.V. All rights reserved.Financial support of the Spanish Ministry of Economy and Competitiveness (projects MAT2012-39290-C02-02 and SEV-2012-0267) is gratefully acknowledged. Dr. E.M. Rivero thanks the Cursol Foundation for a post-doctoral scholarship.Botella Asuncion, P.; Rivero-Buceta, EM. (2017). Safe approaches for camptothecin delivery: Structural analogues and nanomedicines. Journal of Controlled Release. 247:28-54. https://doi.org/10.1016/j.jconrel.2016.12.023S285424

Peptide hormones and lipopeptides: from self-assembly to therapeutic applications

This review describes the properties and activities of lipopeptides and peptide hormones and how the lipidation of peptide hormones could potentially produce therapeutic agents combating some of the most prevalent diseases and conditions. The self-assembly of these types of molecules is outlined, and how this can impact on bioactivity. Peptide hormones specific to the uptake of food and produced in the gastrointestinal tract are discussed in detail. The advantages of lipidated peptide hormones over natural peptide hormones are summarised, in terms of stability and renal clearance, with potential application as therapeutic agent

Amine-functionalized mesoporous silica materials for heterogenization of organotransition metal catalysts.

U719-U71

Elucidation of crystal form diversity of the HIV protease inhibitor ritonavir by high-throughput crystallization

Pharmaceutical compounds are molecular solids that frequently exhibit polymorphism of crystal form. One high profile case of polymorphism was ritonavir, a peptidomimetic drug used to treat HIV-1 infection and introduced in 1996. In 1998, a lower energy, more stable polymorph (form II) appeared, causing slowed dissolution of the marketed dosage form and compromising the oral bioavailability of the drug. This event forced the removal of the oral capsule formulation from the market. We have carried out high-throughput crystallization experiments to comprehensively explore ritonavir form diversity. A total of five forms were found: both known forms and three previously unknown forms. The novel forms include a metastable polymorph, a hydrate phase, and a formamide solvate. The solvate was converted to form I via the hydrate phase by using a simple washing procedure, providing an unusual route to prepare the form I “disappearing polymorph” [Dunitz, J. D. & Bernstein, J. (1995) Acc. Chem. Res. 28, 193–200]. Crystals of form I prepared by using this method retained the small needle morphology of the solvate and thus offer a potential strategy for particle size and morphology control