Lipid-based Vesicles Research Articles

Lipid-Based Vesicles: a Non-invasive Tool for Transdermal Drug Delivery

Lipid-Based Vesicles: a Non-invasive Tool for Transdermal Drug Delivery

Melatonin-Loaded Nanocarriers: New Horizons for Therapeutic Applications.

The use of nanosized particles has emerged to facilitate selective applications in medicine. Drug-delivery systems represent novel opportunities to provide stricter, focused, and fine-tuned therapy, enhancing the therapeutic efficacy of chemical agents at the molecular level while reducing their toxic effects. Melatonin (N-acetyl-5-methoxytriptamine) is a small indoleamine secreted essentially by the pineal gland during darkness, but also produced by most cells in a non-circadian manner from which it is not released into the blood. Although the therapeutic promise of melatonin is indisputable, aspects regarding optimal dosage, biotransformation and metabolism, route and time of administration, and targeted therapy remain to be examined for proper treatment results. Recently, prolonged release of melatonin has shown greater efficacy and safety when combined with a nanostructured formulation. This review summarizes the role of melatonin incorporated into different nanocarriers (e.g., lipid-based vesicles, polymeric vesicles, non-ionic surfactant-based vesicles, charge carriers in graphene, electro spun nanofibers, silica-based carriers, metallic and non-metallic nanocomposites) as drug delivery system platforms or multilevel determinations in various in vivo and in vitro experimental conditions. Melatonin incorporated into nanosized materials exhibits superior effectiveness in multiple diseases and pathological processes than does free melatonin; thus, such information has functional significance for clinical intervention.

Engineering soluble artificial epidermal growth factor receptor mimics capable of spontaneous in vitro dimerization.

Epidermal growth factor receptor (EGFR) is a clinically validated target for a multitude of human cancers. The receptor is activated upon ligand binding through a critical dimerization step. Dimerization can be replicated in vitro by locally concentrating the receptor kinase domains on the surface of lipid-based vesicles. In this study we investigated the use of coiled coils to induce spontaneous receptor kinase domain dimerization in vitro to form non-membrane-bound artificial receptor mimics in solution. Two engineered forms of EGFR kinase domain fused to coiled coil complementary peptides were designed to self-associate upon mixing. Two fusion protein species (P3-EGFR and P4-EGFR) independently showed the same activity and polymerization profile known to exist with EGFR kinase domains. Upon mixing the two species, coiled coil heterodimers were formed that induced EGFR association to form dimers of the kinase domains. This was accompanied by 11.5-fold increase in the phosphorylation rate indicative of kinase domain activation equivalent to the levels achieved using vesicle localization and mimicking in vivo ligand-induced activation. This study presents a soluble tyrosine kinase receptor mimic capable of spontaneous in vitro activation that can facilitate functional and drug discovery studies for this clinically important receptor class.

Microfluidic production and characterization of biofunctionalized giant unilamellar vesicles for targeted intracellular cargo delivery

Lipid-based vesicles have found widespread applications in the life sciences, allowing for fundamental insights into membrane-based processes in cell biology and as carrier systems for drug delivery purposes. So far, mostly small unilamellar vesicles (SUVs) with diameters of ~100 nm have been applied as carrier systems for biomedical applications. Despite this progress, several systematic limitations have arisen due to SUV dimensions, e.g., the size and total amount of applicable cargo is limited. Giant unilamellar vesicles (GUVs) might offer a pragmatic alternative for efficient cargo delivery. However, due to the lack of reliable high-throughput production technologies for GUV-carrier systems, only little is known about their interaction with cells. Here we present a microfluidic-based mechanical droplet-splitting pipeline for the production of carrier-GUVs with diameters of ~2 μm. The technology developed allows for highly efficient cargo loading and unprecedented control over the biological and physicochemical properties of GUV membranes. By generating differently charged (between −31 and + 28 mV), bioligand-conjugated (e.g. with E-cadherin, NrCam and antibodies) and PEG-conjugated GUVs, we performed a detailed investigation of attractive and repulsive GUV-cell interactions. Fine-tuning of these interactions allowed for targeted cellular GUV delivery. Moreover, we evaluated strategies for intracellular GUV cargo release by lysosomal escape mediated by the pH sensitive lipid DOBAQ, enabling cytoplasmic transmission. The presented GUV delivery technology and the systematic characterization of associated GUV-cell interactions could provide a means for more efficient drug administration and will pave the way for hitherto impossible approaches towards a targeted delivery of advanced cargo such as microparticles, viruses or macromolecular DNA-robots.

A Comprehensive Review of Cancer MicroRNA Therapeutic Delivery Strategies.

In the field of molecular oncology, microRNAs (miRNAs) and their role in regulating physiological processes and cancer pathogenesis have been a revolutionary discovery over the last decade. It is now considered that miRNA dysregulation influences critical molecular pathways involved in tumor progression, invasion, angiogenesis and metastasis in a wide range of cancer types. Hence, altering miRNA levels in cancer cells has promising potential as a therapeutic intervention, which is discussed in many other articles in this Special Issue. Some of the most significant hurdles in therapeutic miRNA usage are the stability and the delivery system. In this review, we cover a comprehensive update on the challenges and strategies for the development of therapeutic miRNA delivery systems that includes virus-based delivery, non-viral delivery (artificial lipid-based vesicles, polymer-based or chemical structures), and recently emerged extracellular vesicle (EV)-based delivery systems.

Lipid Vesicles and Nanoparticles for Non-invasive Topical and Transdermal Drug Delivery.

The delivery of drugs, via different layers of skin, is challenging because it acts as a natural barrier and exerts hindrance against molecules to permeate into or through it. To overcome such obstacles, different noninvasive methods, like vehicle-drug interaction, modifications of the horny layer and nanoparticles have been suggested. The aim of the present review is to highlight some of the non-invasive methods for topical, diadermal and transdermal delivery of drugs. Special emphasis has been made on the information available in numerous research articles that put efforts in overcoming obstacles associated with barrier functions imposed by various layers of skin. Advances have been made in improving patient compliance that tends to avoid hitches involved in oral administration. Of particular interest is the use of lipid-based vesicles and nanoparticles for dermatological applications. These particulate systems can effectively interact and penetrate into the stratum corneum via lipid exchange and get distributed in epidermis and dermis. They also have the tendency to exert a systemic effect by facilitating the absorption of an active moiety into general circulation.

Development of rosuvastatin flexible lipid-based nanoparticles: promising nanocarriers for improving intestinal cells cytotoxicity

BackgroundRosuvastatin (RSV) is a poorly water-soluble drug that has an absolute oral bioavailability of only 20%. The aim of this work was to prepare a positively charged chitosan coated flexible lipid-based vesicles (chitosomes) and compare their characteristics to the corresponding negatively charged flexible liposomal nanoparticles (NPs) in order to develop new RSV nanocarrier systems.MethodsThree formulation factors affecting the development of chitosomes nano-formulation were optimized for their effects on the particles size, entrapment efficiency (EE) and zeta potential. The optimized flexible chitosomes and their corresponding liposomal NPs were characterized for morphology, in vitro release, flexibility and intestinal cell viability. The half maximum inhibitory concentrations (IC50) for both formulations were calculated.ResultsThe drug to lipid molar ratio, edge activator percent and the chitosan concentration were significantly affecting the characteristics of NPs. The optimized chitosomes nano-formulation exhibited larger size, higher EE and greater zeta potential value when compared to the corresponding liposomal NPs. Both formulations showed a spherical shape nanostructure with a marked outer shell for the chitosomes nano-formulation. Chitosomes illustrated an extended drug release profile when compared with the corresponding liposomal NPs and the prepared drug suspension. Flexibility of both vesicles was confirmed with superiority of liposomal NPs over chitosomes. RSV loaded chitosomes nano-formulation exhibited lower IC50 values and higher therapeutic window while liposomal NPs were compatible with the intestinal cells.ConclusionsRSV loaded chitosomes nano-formulation could be considered as a promising nanocarrier system with a marked cytotoxic activity while, RSV loaded liposomal NPs are suitable nanocarrier to improve RSV activity in treatment of cardiovascular disorders.

CCD based development and characterization of nano-transethosome to augment the antidepressant effect of agomelatine on Swiss albino mice

This study was intended to develop and optimize agomelatine loaded lipid-based transdermal vesicles (AGLTVs) for the treatment of depression. For the optimization purpose, central composite design was used and the selected independent variables were phospholipid and ethanol. The individual and joined impacts of independent variables were assessed on vesicle size, PDI, and encapsulation efficiency. Further, the optimized agomelatine loaded lipid transethosomes vesicle (AGLTVopt) was evaluated for drug release, skin penetration potential, physicochemical properties and preclinical antidepressant effect on Swiss albino mice. AGLTVopt showed low vesicle size (156.8 nm), high entrapment efficiency (78.57%) and enhanced transdermal flux (18.75 μg/cm2/h). Finally, AGLTVopt was converted to a Carbopol-934 based gel for the ease of transdermal application. The confocal laser scanning microscopy study results also showed enhanced permeation of Rhodamine-B containing AGLTVopt-gel to the deeper layer of skin. The drug release study showed prolonged release of agomelatine and the drug release kinetics followed the Higuchi model. The in-vivo antidepressant activity presented greater improvement in the behavior of AGLTVopt-gel treated group. The histopathology of skin revealed no sign of irritation. This study concluded that the AGLTVopt-gel can be a safe formulation for the brain delivery of agomelatine via transdermal route.

Partially Polymerized Phospholipid Vesicles for Efficient Delivery of Macromolecules.

Lipid-based vesicles, namely cationic liposomal nanocarriers have been recognized early on as one of the most attractive delivery systems for RNA, protein, and oligonucleotides. Despite several advantages of conventional liposomal carriers for therapeutic macromolecules, their flexible and unsupported bilayered membranes can pose some limitations for efficient intracellular delivery of their sensitive cargos. Hence, polymerized liposomes, a concept conceived about 20years ago, might offer structural solution to current in vivo efficiency concerns affecting traditional cationic phospholipid vectors, especially when adapted to enable superior loading and stability, typically required for effective intracellular delivery of proteins and polynucleotides.Our recent approach attempted to remodel polymerized liposomal vesicles-specifically their semi-rigid membrane structure-to create block-polymerized bilayered vesicles (generally composed of DOTAP: DOPE: Diyne PC in 0.1:1:1 molar ratio). Adopting a modified freeze-dry-rehydration technique allowed modular reassembly of such partially polymerized lipidic vesicles (PPL). Different prototype cationic partially polymerized liposomal preparations (PPLs) were successfully developed (mean particle size range 150-300nm), demonstrating enhanced physicochemical stability and loading capacity, thus promoting improved intracellular delivery of model RNAi and protein cargos.

Extracellular Vesicles: Opportunities and Challenges for the Treatment of Renal Fibrosis.

Extracellular vesicles (EVs) are small lipid-based membrane-bound vesicles secreted by most cells under both physiological and pathological conditions. A key function of EVs is to mediate cell-cell communication via transferring mRNAs, miRNAs and proteins from parent cells to recipient cells. These unique features of EVs have spurred a renewed interest in their utility for therapeutics. Given the growing evidence for EV-mediated renal diseases, strategies that could block the release or uptake of pathogenic EVs will be discussed in this review. Then, the therapeutic potential of EVs predominantly from stem cells in renal diseases will be outlined. Finally, we will focus on the specific application of EVs as a novel drug delivery system and highlight the challenges of EVs-based therapies for renal diseases.

Characterization of Biocompatible Lipid-Based Vesicles Contained with Medicinal Herb Extracts

In order to increase the medicinal herbs efficiency of drug delivery, vesicles contained with medicinal herbs were prepared by phosphatidylcholines and surface active agent. Vesicles loaded with medicinal herbs were characterized by UV-spectroscopy, Zetasizer. The antioxidant activity of vesicles was measured by DPPH assay and ABTS radical scavenging assays. Also, an analysis was conducted to determine the effects of anti-inflammatory of vesicles contained medicinal herbs. In addition, the whitening effects of vesicles contained medicinal herbs extract were studied via tyrosinase inhibition assay. The results of vesicles were as follows. Vesicles appeared an average diameter of approximatively 164-599 nm. All studied vesicles contained with medicinal herbs showed antioxidant, anti-inflammatory and whitening effects in a dose-dependent manner. Therefore, this experiment achieves its purpose of synthesizing of vesicles. In conclusion, we recommended that the vesicles loaded with medicinal herbs have ability for anti-aging materials. Specifically, it will apply to cosmetic ingredients.

Synthetic Cells Synthesize Therapeutic Proteins inside Tumors.

Synthetic cells, artificial cell-like particles, capable of autonomously synthesizing RNA and proteins based on a DNA template, are emerging platforms for studying cellular functions and for revealing the origins-of-life. Here, it is shown for the first time that artificial lipid-based vesicles, containing the molecular machinery necessary for transcription and translation, can be used to synthesize anticancer proteins inside tumors. The synthetic cells are engineered as stand-alone systems, sourcing nutrients from their biological microenvironment to trigger protein synthesis. When pre-loaded with template DNA, amino acids and energy-supplying molecules, up to 2 × 107 copies of green fluorescent protein are synthesized in each synthetic cell. A variety of proteins, having molecular weights reaching 66 kDa and with diagnostic and therapeutic activities, are synthesized inside the particles. Incubating synthetic cells, encoded to secrete Pseudomonas exotoxin A (PE) with 4T1 breast cancer cells in culture, resulted in killing of most of the malignant cells. In mice bearing 4T1 tumors, histological evaluation of the tumor tissue after a local injection of PE-producing particles indicates robust apoptosis. Synthetic cells are new platforms for synthesizing therapeutic proteins on-demand in diseased tissues.

Enhanced non invasive trans-tympanic delivery of ciprofloxacin through encapsulation into nano-spanlastic vesicles: Fabrication, in-vitro characterization, and comparative ex-vivo permeation studies

The aim of this research was to encapsulate ciprofloxacin, a broad spectrum fluoroquinolone antibiotic, into Span 60 based nano-elastic vesicles, nano-spanlastics, for accomplishing improved non invasive trans-tympanic delivery, providing means for ototopical treatment of acute otitis media (AOM). To achieve this purpose, ciprofloxacin-loaded nano-spanlastics were prepared by thin film hydration (TFH) technique, using several non-ionic edge activators (EAs) according to full factorial design (32). The investigation of the effect of formulation variables on nano-spanlastic characteristics and selection of the optimum formula were performed using Design-Expert® software. The selected formulation was also subjected to comparative ex-vivo permeation studies through tympanic membrane (TM) of rabbits. Results revealed that the optimal nano-spanlastic formulation (S-2; containing 20% Brij 35 as an EA) exhibited nano-sized spherical vesicles (287.55±9.97nm), relatively high entrapment efficiency percent (51.81±1.57%), and good physical stability after six months of storage at 4–8°C. Ex-vivo TM permeation studies demonstrated the superiority of the optimal nano-spanlastic formulation over the commercial Ciprocin® drops. However, when compared to lipid-based elastic vesicles, nano-transfersomes, nano-spanlastics exhibited lower drug permeation through the TM. Concisely, the obtained results suggested that nano-spanlastics can be promising for improving trans-tympanic delivery of ciprofloxacin.

USE OF LACTIC ACID AND SPAN 80 IN THE FORMULATION OF LIPID BASED IMIQUIMOD VESICLES FOR GENITAL WARTS

<p><strong>Objective: </strong>The objective of present study was formulation development of imiquimod using lactic acid and span 80 for topical delivery to cure genital warts.</p><p><strong>Methods: </strong>Lipid based vesicles (LBV) of 2% imiquimod were prepared with phospholipoin 90G, ethanol, lactic acid and span 80 using central composite design. The prepared vesicles were optimized statistically and characterized for particle size, zeta potential, percentage entrapment efficiency (% EE) and transmission electron microscopy (TEM). The optimized LBV were incorporated into gel formulation which was evaluated and compared with control gel and marketed formulation.</p><p><strong>Results: </strong>The optimized vesicles had particle size 394.8±9.6 nm, zeta potential-16.5±2.5 mV, % EE 88.27±0.45 and TEM study confirmed the formation of vesicular structure with spherical shape. The gel formulation of imiquimod vesicles showed positive results like spreadability 14.3±0.34 gcm/s, viscosity 13500±1.67 cp, consistency 6.1±0.14 mm and extrudability 16.47±0.11 g/cm<sup>2</sup>. <em>In vitro</em> permeation amount of drug was remarkably lower (10.13 %) than control (87.17 %) and marketed formulation (27.46 %). Results of retained drug for both <em>in vitro</em> as well as <em>in vivo</em> permeation study and local accumulation efficiency (4.021±0.2292) were considerably higher for LBV gel than control (0.1008±0.002513) and marketed formulation (0.8314±0.0300). To understand the mechanism of interaction between skin and vesicles, fourier transform infra-red spectroscopy studies were also done. Results of skin irritancy test and histological examination revealed biocompatible nature of formulation.</p><p><strong>Conclusion: </strong>Results of <em>in vitro </em>and <em>in vivo</em> studies indicated that this vesicle gel formulation provided efficient and site specific dermal delivery of imiquimod for cure of genital warts.</p>

The Silencing of <i>Septin 1</i> via Synthetic siRNAs in <i>Schizosaccharomyces pombe</i>

Septins are evolutionary conserved GTP-binding proteins and form heterooligomers in cells to interact with cytoskeleton. The main roles of septins in cell are cytokines, membrane interactions, vesicle trafficking and microtubule and actin organization. Non-coding RNAs are key players of gene expression regulation. Small-interfering RNAs (siRNAs) belong to non-coding RNAs, are characterized by sequence complementarity to their target mRNAs. siRNAs silence their targets via mRNA degradation or inhibition of translation. In S. pombe siRNAs can also propagate heterochromatin to silence genes located in centromeric regions. In this study, the aim was understanding the results of extrinsically induced siRNA silencing in S. pombe by using synthetic siRNAs specific to Septin 1 gene. siRNAs were introduced to cells by lipid-based vesicles and the alterations in Septin 1 expressions were monitored with qPCR. Septin 1 expression was reduced dramatically via direct siRNA introduction to cells. The interactions between cell morphology and the reduced level of Septin 1 were observed after accomplishing the silencing of Septin 1 gene. In this study, it is shown that the morphology of the cells is affected by the reduced levels of Septin 1 expression and the cells form long and chain-like structures. This study constitutes an important example in understanding the results of inducing siRNA silencing extrinsically in S. pombe.

Resource Sharing Controls Gene Expression Bursting.

Episodic gene expression, with periods of high expression separated by periods of no expression, is a pervasive biological phenomenon. This bursty pattern of expression draws from a finite reservoir of expression machinery in a highly time variant way, i.e., requiring no resources most of the time but drawing heavily on them during short intense bursts, that intimately links expression bursting and resource sharing. Yet, most recent investigations have focused on specific molecular mechanisms intrinsic to the bursty behavior of individual genes, while little is known about the interplay between resource sharing and global expression bursting behavior. Here, we confine Escherichia coli cell extract in both cell-sized microfluidic chambers and lipid-based vesicles to explore how resource sharing influences expression bursting. Interestingly, expression burst size, but not burst frequency, is highly sensitive to the size of the shared transcription and translation resource pools. The intriguing implication of these results is that expression bursts are more readily amplified than initiated, suggesting that burst formation occurs through positive feedback or cooperativity. When extrapolated to prokaryotic cells, these results suggest that large translational bursts may be correlated with large transcriptional bursts. This correlation is supported by recently reported transcription and translation bursting studies in E. coli. The results reported here demonstrate a strong intimate link between global expression burst patterns and resource sharing, and they suggest that bursting plays an important role in optimizing the use of limited, shared expression resources.

Aggregation of Phospholipid Based Vesicle Using Triblock Polymer

ABSTRACTThe motivation of this study is to learn more about the effect of lipid to polymer ratios on the biosensing platform in lipid-based vesicles. Nanoparticles are useful because of their ability to detect cancer in the body with the aid of antibodies. This early detection is crucial in avoiding the rapid spread of tumors. In this study, nanoparticles were synthesized for bio-sensing applications. This was accomplished by combining a long chain lipid (dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) and a short chain lipid (diheptanoyl-sn-glycero-3-phosphocholine, DHPC). After this, the nanoparticles underwent a temperature cycling procedure. Next, the nanoparticles went through a 100nm extrusion filter. This transformed the multilamellar vesicles (MLVs) into unilamellar vesicles (ULVs). The polymer (polypropylene oxide - polyethylene oxide - polypropylene oxide) was then added to the samples, which served as a linker to create a cluster of ULVs. The clustering process was monitored using apparent UV absorption and dynamic light scattering. Dynamic light scattering reflects the hydrodynamic radius of the particle and UV absorption records the change in turbidity. If large clusters are formed, then both the UV absorption and the hydrodynamic radius will increase. Three different polymer to lipid ratios were used: 2.5:1, 1:1, and 0.5:1. The results show that with an increase of polymer to lipid ratios, the aggregation process was facilitated. The nanoparticles were fabricated at the Self-Assembled Functional Nanomaterials (SAFN) lab under the mentorship of Professor Mu-Ping Nieh. The results of this study could provide a more effective way to detect malignant cancer cells in susceptible patients.

Liposomal drug delivery system

Lipid-based self-assembling vesicles were first described in 1961 and reported in 1964 by Dr. Alec D. Bangham (Bangham and Horne in J Mol Biol 8:660–668, 1964) at the Babraham Institute in Cambridge, UK, in which he wrote: “It is probable that at equilibrium each and every lipid bilayer forms an unbroken membrane-there being no exposed hydrocarbon/water interface-from which it follows that every aqueous compartment would be discrete and isolated from its neighbor, including a complete separation of the outermost compartment of the whole structure from the continuous phase in which it is suspended”. It is thermodynamically possible for each lipid bilayer to form a discrete membrane, separating the vesicle from the continuous aqueous phase in which it is suspended. These “unbroken membranes” were called as “liquid crystal” or “smectic mesophase”, “Bangasomes” after the name of Dr. Bangham, and finally “liposomes”. The word “liposome” derives from two Greek words of “lipo-meaning fat” and “soma-meaning body”. In the earlier days, these artificial vesicles (or liposomes) were used for the study of cell physiology such as ion (or drug) permeability, membrane fusion, membrane-bound enzyme properties or as a membrane model. More recently, much attention was brought to the uses of liposomes in medical fields as drug delivery systems and the first article of this kind was published in 1971 in FEBS Letters by Dr. George Gregoriadis and his co-workers, where amyloglucosidase and albumin were entrapped into liposome for the purpose of enzyme replacement therapy (Gregoriadis et al. in FEBS Lett 14(2):95–99, 1971). Since then, tremendous amounts of papers were published on the uses of liposomes as a drug delivery system (DDS). So, this mini-review is mainly focused on the use of liposome as DDS.

Enhancement of Lateral Diffusion in Catanionic Vesicles during Multilamellar-to-Unilamellar Transition.

Catanionic vesicles are formed spontaneously by mixing cationic and anionic dispersions in aqueous solution in suitable conditions. Because of spontaneity in formation, long-term stability, and easy modulation of size and charge, they have numerous advantages over conventional lipid-based vesicles. The dynamics of such vesicles is of interest in the field of biomedicine, as they can be used to deliver drug molecules into the cell membrane. Dynamics of catanionic vesicles based on sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB) have been studied using incoherent elastic and quasielastic neutron scattering (QENS) techniques. Neutron scattering experiments have been carried out on two backscattering spectrometers, IRIS and IN16B, which have different energy resolutions and energy transfer windows. An elastic fixed-window scan carried out using IN16B shows a phase transition at ∼307 K during the heating cycle, whereas on cooling the transition occurred at ∼294 K. DSC results are found to be in close agreement with the elastic scan data. This transition is ascribed to a structural rearrangement from a multilamellar to a unilamellar phase [ Andreozzi J. Phys. Chem. B 2010 , 114 , 8056 - 8060 ]. It is found that a model in which the surfactant molecules undergo both lateral and internal motions can describe the QENS data quite well. While the data from IRIS have contributions from both dynamical processes, the data from IN16B probe only lateral motions, as the internal motions are too fast for the energy window of the spectrometer. It is found that, through the transition, the fraction of surfactant molecules undergoing lateral motion increases of a factor of 2 from the multilamellar to the unilamellar phase, indicating an enhanced fluidity of the latter. The lateral motion is found to be Fickian in nature, while the internal motion has been described by a localized translational diffusion model. The results reported here could have direct interest for a number of applications, such as molecular transport, and the effect of specific drug molecules or hormones through the membrane.

Capable Cross-links: Polymersomes Reinforced with Catalytically Active Metal–Ligand Bonds

Polymersomes, hollow spherical nano-to-microscale polymer assemblies, have increasingly become important constructs in the development of biomimetic materials that expand the library of functional and robust analogs to lipid-based vesicles. As compared to liposomes, polymersomes possess superior physical properties and the nearly unlimited potential for synthetic fine-tuning. Herein we improve on the physical properties of these polymer vesicles by introducing platinum-based metal–ligand cross-links into the hydrophobic core, which gave the vesicles demonstrated resistance to destabilization by surfactants over un-cross-linked polymersomes. The formation of cross-links was capable of being selectively reversed by the addition of phosphines. In addition, the Pt(0) cross-links retained their catalytic activity for the hydrosilylation of alkenes.