Malvern Cosmeceutics partners with leading academic groups and industry innovators to harness Lipodisq® technology. Together we are shaping the next generation of targeted pharmaceutical solutions, enhancing delivery, boosting stability and overcoming solubility challenges.
Physicochemical Characterization, Toxicity and In Vivo Biodistribution Studies of a Discoidal, Lipid-Based Drug Delivery Vehicle: Lipodisq Nanoparticles Containing Doxorubicin
Many promising pharmaceutically active compounds have low solubility in aqueous environments and their encapsulation into efficient drug delivery vehicles is crucial to increase their bioavailability. Lipodisq nanoparticles are approximately 10 nm in diameter and consist of a circular phospholipid bilayer, stabilized by an annulus of SMA (a hydrolysed copolymer of styrene and maleic anhydride). SMA is used extensively in structural biology to extract and stabilize integral membrane proteins for biophysical studies. Here, we assess the potential of these nanoparticles as drug delivery vehicles, determining their cytotoxicity and the in vivo excretion pathways of their polymer and lipid components. Doxorubicin-loaded Lipodisq were cytotoxic across a panel of cancer cell lines, whereas nanoparticles without the drug had no effect on cell proliferation. Intracellular doxorubicin release from Lipodisq in HeLa cells occurred in the low-pH environment of the endolysosomal system, consistent with the breakdown of the discoidal structure as the carboxylate groups of the SMA polymer become protonated. Biodistribution studies in mice showed that, unlike other nanoparticles injected intravenously, most of the Lipodisq components were recovered in the colon, consistent with rapid uptake by hepatocytes and excretion into bile. These data suggest that Lipodisq have the potential to act as delivery vehicles for drugs and contrast agents.
A small-molecule TLR4 antagonist reduced neuroinflammation in female E4FAD mice
APOE genotype is the greatest genetic risk factor for sporadic Alzheimer’s disease (AD). APOE4 increases AD risk up to 12-fold compared to APOE3, an effect that is greater in females. Evidence suggests that one-way APOE could modulate AD risk and progression through neuroinflammation. Indeed, APOE4 is associated with higher glial activation and cytokine levels in AD patients and mice. Therefore, identifying pathways that contribute to APOE4-associated neuroinflammation is an important approach for understanding and treating AD. Human and in vivo evidence suggests that TLR4, one of the key receptors involved in the innate immune system, could be involved in APOE-modulated neuroinflammation. Consistent with that idea, we previously demonstrated that the TLR4 antagonist IAXO-101 can reduce LPS- and Aβ-induced cytokine secretion in APOE4 glial cultures. Therefore, the goal of this study was to advance these findings and determine whether IAXO-101 can modulate neuroinflammation, Aβ pathology, and behaviour in mice that express APOE4.
The synthetic glycolipid-based TLR4 antagonist FP7 negatively regulates in vitro and in vivo haematopoietic and non-haematopoietic vascular TLR4 signalling
TLRs, including TLR4, have been shown to play a crucial role in cardiovascular inflammatory-based diseases. The main goal of this study was to determine the potential of FP7, a synthetic glycolipid active as a TLR4 antagonist, to modulate haematopoietic and non-haematopoietic vascular TLR4 pro-inflammatory signalling. HUVEC, human THP-1 monocytes, THP-1-derived macrophages, mouse RAW-264.7 macrophages and Angiotensin II-infused apolipoprotein E-deficient mice were in vitro and in vivo models, respectively. Western blotting, Ab array and ELISA approaches were used to explore the effect of FP7 on TLR4 functional activity in response to bacterial LPS (in vitro) and endogenous ligands of sterile inflammation (in vitro and in vivo). Following activation of TLR4, in vitro and in vivo data revealed that FP7 inhibited p38 MAPK and p65 NF-kB phosphorylation associated with down-regulation of a number of TLR4-dependent pro-inflammatory proteins. In addition to inhibition of LPS-induced TLR4 signalling, FP7 negatively regulated TLR4 activation in response to ligands of sterile inflammation (hydroperoxide-rich oxidised LDL, in vitro and Angiotensin II infusion, in vivo). These results demonstrate the ability of FP7 to negatively regulate in vitro and in vivo haematopoietic and non-haematopoietic vascular TLR4 signalling both in humans and mice, suggesting the potential therapeutic use of this TLR4 antagonist for pharmacological intervention of vascular inflammatory diseases.
Novel Nanoparticle Targeting of Antimicrobials to Infected Diabetic Foot Ulcers; Innovate Award, Biomedical Catalyst
Collaborative feasibility study between three partners based in the West Midlands; Malvern Cosmeceutics Limited, the School of Biology, Chemistry & Forensic Science and the School of Biomedical Science and Physiology both at University of Wolverhampton together with clinical oversight from New Cross Hospital Wolverhampton, focussed on applying MCL’s proprietary nanoparticle delivery system, Lipodisq®, for topical treatment of infected diabetic foot ulcers (DFUs). Particular attention will be placed on improved targeting of existing approved drugs to Gram(-) bacteria especially those likely to develop multi-drug resistance (MDR) and implicated as the causative organisms in the development of severe and recurrent cases of DFUs, treatment of which currently consumes approx 1% of the NHS budget (£662 Million per annum). The commercial objective is to develop a high value, topical pharma product, future-proofed to overcome evolving bacterial resistance mechanisms, suitable for clinical trial, local manufacture and global distribution either directly by MCL or in partnership with UK-based wound care companies.
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A range of key pharmaceutical compounds, both novel and generic, are available from our trusted partners for pharmaceutical research, covering anti-inflammatory agents, retinoid compounds, anti-infectives and anti-viral compounds.
Malvern Cosmeceutics engages in R&D collaborations with organisations seeking external innovation to expand and accelerate their development pipelines. The Lipodisq® encapsulation platform enables efficient transition from early formulation screening to proof‑of‑concept and clinical evaluation. By enhancing the bioavailability, physicochemical stability, and functional efficacy of active compounds—without requiring chemical derivatisation—Lipodisq® supports streamlined development of high‑performance transdermal and systemic delivery systems.
