Hydrophobic Cargo Research Articles

Targeted Plasma Membrane Delivery of a Hydrophobic Cargo Encapsulated in a Liquid Crystal Nanoparticle Carrier

The controlled delivery of drug/imaging agents to cells is critical for the development of therapeutics and for the study of cellular signaling processes. Recently, nanoparticles (NPs) have shown significant promise in the development of such delivery systems. Here, a liquid crystal NP (LCNP)-based delivery system has been employed for the controlled delivery of a water-insoluble dye, 3,3′-dioctadecyloxacarbocyanine perchlorate (DiO), from within the NP core to the hydrophobic region of a plasma membrane bilayer. During the synthesis of the NPs, the dye was efficiently incorporated into the hydrophobic LCNP core, as confirmed by multiple spectroscopic analyses. Conjugation of a PEGylated cholesterol derivative to the NP surface (DiO-LCNP-PEG-Chol) enabled the binding of the dye-loaded NPs to the plasma membrane in HEK 293T/17 cells. Time-resolved laser scanning confocal microscopy and Förster resonance energy transfer (FRET) imaging confirmed the passive efflux of DiO from the LCNP core and its insertion into the plasma membrane bilayer. Finally, the delivery of DiO as a LCNP-PEG-Chol attenuated the cytotoxicity of DiO; the NP form of DiO exhibited ~30-40% less toxicity compared to DiOfree delivered from bulk solution. This approach demonstrates the utility of the LCNP platform as an efficient modality for the membrane-specific delivery and modulation of hydrophobic molecular cargos.

Targeted Plasma Membrane Delivery of a Hydrophobic Cargo Encapsulated in a Liquid Crystal Nanoparticle Carrier.

The controlled delivery of drug/imaging agents to cells is critical for the development of therapeutics and for the study of cellular signaling processes. Recently, nanoparticles (NPs) have shown significant promise in the development of such delivery systems. Here, a liquid crystal NP (LCNP)-based delivery system has been employed for the controlled delivery of a water-insoluble dye, 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO), from within the NP core to the hydrophobic region of a plasma membrane bilayer. During the synthesis of the NPs, the dye was efficiently incorporated into the hydrophobic LCNP core, as confirmed by multiple spectroscopic analyses. Conjugation of a PEGylated cholesterol derivative to the NP surface (DiO-LCNP-PEG-Chol) enabled the binding of the dye-loaded NPs to the plasma membrane in HEK 293T/17 cells. Time-resolved laser scanning confocal microscopy and Förster resonance energy transfer (FRET) imaging confirmed the passive efflux of DiO from the LCNP core and its insertion into the plasma membrane bilayer. Finally, the delivery of DiO as a LCNP-PEG-Chol attenuated the cytotoxicity of DiO; the NP form of DiO exhibited ~30-40% less toxicity compared to DiOfree delivered from bulk solution. This approach demonstrates the utility of the LCNP platform as an efficient modality for the membrane-specific delivery and modulation of hydrophobic molecular cargos.

Determining Interactions of Cationic Membrane Nanoparticles with Hydrophobic Drug Cargo and their Mechanisms of Drug Delivery to Cells

Paclitaxel (PTXL), a member of the taxane family of mitotic inhibitors, is a widely used cancer drug. The first PTXL clinical incarnation (Taxol®) employs the non-ionic surfactant, Cremophor® EL—which itself causes hypersensitivity reactions—to solubilize hydrophobic PTXL. Second generation alternatives to deliver PTXL include Abraxane® and EndoTAG® (a liposomal formulation), which achieve limited passive tumor targeting and are still associated with typical chemotherapy side effects. In order to make a substantial therapeutic improvement, delivery vehicles must concentrate more PTXL in tumors and interact less with healthy tissue (Int J Pharm Sci Rev Res 2015, 31, 205; J Cont Release 2012, 163, 322; Chem Rev 2016, 116, 3883). Lipid nanoparticles have many advantages as drug delivery agents including a diverse set of lipid building blocks to tune physical and chemical properties, as well as their ease of modular fabrication. We demonstrate the ability to alter the drug-loading capacity of liposomes and the nanoparticle-cell interactions by changing the lipid composition to affect membrane charge density, steric stabilization, hydrophobic domain disorder, and lipid shape (which determines membrane curvature). Here, we present results that indicate the importance of tail structure for hydrophobic drug loading and retention. We have also observed a non-monotonic drug delivery dependence on the amount of PTXL incorporated into liposomes. Preliminary results reveal a significant divergence from the known tenets governing liposome-based gene delivery to those that determine small molecule hydrophobic drug delivery. In order to develop a set of design principles for the latter, a systematic understanding of how liposome formulation dictates the nanoparticle's subsequent path in vitro and in vivo is essential. Novel liposome formulations achieve in vitro outcomes equal to and better than the stage III formula EndoTAG®.

Amphiphilic Imbalance and Stabilization of Block Copolymer Micelles on-Demand through Combinational Photo-Cleavage and Photo-Crosslinking.

An amphiphilic block copolymer of poly(ethylene oxide)-b-poly((N-methacryloxy phthalimide)-co-(7-(4-vinyl-benzyloxyl)-4-methylcoumarin)) (PEO45 -b-P(MAPI36 -co-VBC4 )) is designed to improve the micellar stability during the photo-triggered release of hydrophobic cargoes. Analysis of absorption and emission spectra, solution transmittance, dynamic light scattering, and transmission electron microscopy supports that polymer micelles of PEO45 -b-P(MAPI36 -co-VBC4 ) upon the combinational irradiation of 365 and 254 nm light can be solubilized through the photolysis of phthalimide esters and simultaneously crosslinked via the partially reversible photo-dimerization of coumarins. The photo-triggered release experiment shows that the leakage of doxorubicin molecules from crosslinked micelles can be predictably regulated by controlling the irradiation time of 365 and 254 nm light.

The process of lipid storage in insect oocytes: The involvement of β-chain of ATP synthase in lipophorin-mediated lipid transfer in the chagas’ disease vector Panstrongylus megistus (Hemiptera: Reduviidae)

Lipophorin is the main lipoprotein in the hemolymph of insects. During vitellogenesis, lipophorin delivers its hydrophobic cargo to developing oocytes by its binding to non-endocytic receptors at the plasma membrane of the cells. In some species however, lipophorin may also be internalized to some extent, thus maximizing the storage of lipid resources in growing oocytes. The ectopic β chain of ATP synthase (β-ATPase) was recently described as a putative non-endocytic lipophorin receptor in the anterior midgut of the hematophagous insect Panstrongylus megistus. In the present work, females of this species at the vitellogenic stage of the reproductive cycle were employed to investigate the role of β-ATPase in the transfer of lipids to the ovarian tissue. Subcellular fractionation and western blot revealed the presence of β-ATPase in the microsomal membranes of the ovarian tissue, suggesting its localization in the plasma membrane. Immunofluorescence assays showed partial co-localization of β-ATPase and lipophorin in the membrane of oocytes as well as in the basal domain of the follicular epithelial cells. Ligand blotting and co-immunoprecipitation approaches confirmed the interaction between lipophorin and β-ATPase. In vivo experiments with an anti-β-ATPase antibody injected to block such an interaction demonstrated that the antibody significantly impaired the transfer of fatty acids from lipophorin to the oocyte. However, the endocytic pathway of lipophorin was not affected. On the other hand, partial inhibition of ATP synthase activity did not modify the transfer of lipids from lipophorin to oocytes. When the assays were performed at 4°C to diminish endocytosis, the results showed that the antibody interfered with lipophorin binding to the oocyte plasma membrane as well as with the transfer of fatty acids from the lipoprotein to the oocyte. The findings strongly support that β-ATPase plays a role as a docking lipophorin receptor at the ovary of P. megistus, similarly to its function in the midgut of such a vector. In addition, the role of β-ATPase as a docking receptor seems to be independent of the enzymatic ATP synthase activity.

Selective Release of Hydrophobic and Hydrophilic Cargos from Multi-Stimuli-Responsive Nanogels.

Highly stable multi-stimuli-responsive nanogels for selective release of simultaneously encapsulated hydrophobic and hydrophilic cargos in a spatiotemporally controlled manner are demonstrated here. The nanogel is composed of hydrophilic pH- and thermoresponsive poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and hydrophobic photocleavable o-nitrobenzyl (ONB) linkage. The hydrophobic cargos were noncovalently encapsulated into lipophilic interiors of the nanogels, while the hydrophilic cargos were chemically linked to the nanogel precursor polymer PDMAEMA through a redox-cleavable disulfide junction. For these dual-loaded nanogels, hydrophobic cargos can be released in response to temperature, pH, and UV light, while the hydrophilic cargos can be released in response to redox reagent. The stimuli-selective release of hydrophobic and hydrophilic cargos affords the system with great potential applications in combination chemotherapy, tissue engineering, anticorrosion, and smart nanoreactors.

Effect of Molecular Structure on Stability of Organic Nanoparticles Formed by Bodipy Dimers.

The objective was to evaluate the stability of organic nanoparticles made from Bodipy dimers. Bodipy dimers with different length of linkers were synthesized via multicomponent Passerini reaction, and could form the fluorescent nanoparticles (FNPs) through nanoprecipitation. Bodipy-dimers FNPs with long chain linker indicated better stability in biological condition than those with short one as revealed by changes of diameter and size distribution. The FNPs possessed high physical homogeneity and low cytotoxicity. The molecular structure dependent stability was also validated by confocal laser scanning microscope based on the dissociation-induced fluorescence recovering. Importantly, stable FNPs also could be used to load hydrophobic cargoes and deliver them into cytoplasm. We believe this systematic study between structure and stability might open new opportunities for designing stable nanoparticles for various applications.

Synthesis of star-branched PLA-b-PMPC copolymer micelles as long blood circulation vectors to enhance tumor-targeted delivery of hydrophobic drugs in vivo

Star-branched amphiphilic copolymer nanocarriers with high-density zwitterionic shell show great promise in drug delivery due to their controllable small size and excellent anti-biofouling properties. This gives the hydrophobic cargo with high stability and long blood circulation in vivo. In the present study, star-branched polylactic acid and poly(2-methacryloyloxyethyl phosphorylcholine) copolymers with (AB3)3–type architecture (PLA-b-PMPC3)3 were conceived as drug vectors, and the copolymers were synthesized by an “arm-first” approach via the combination of ring opening polymerization (ROP), atom transfer radical polymerization (ATRP) and the click reaction. The self-assembled star-branched copolymer micelles (sCPM) had an average diameter of about 64.5 nm and exhibited an ultra-hydrophilic surface with an ultralow water contact angle of about 12.7°, which efficiently suppressed the adhesion of serum proteins. In vivo experiments showed that the sCPM loading strongly enhanced the blood circulation time of DiI and the plasma half-life of DiI in sCPM was 19.3 h. The relative accumulation concentration in tumor of DiI delivered by sCPM was 2.37-fold higher than that of PLA-PEG, at 4 h after intravenous injection. These results demonstrated that the star-branched copolymer (PLA-b-PMPC3)3 is a promising alternative carrier material for intravenous delivery versus classic PEG-modified strategies.

On the intracellular release mechanism of hydrophobic cargo and its relation to the biodegradation behavior of mesoporous silica nanocarriers

The intracellular release mechanism of hydrophobic molecules from surface-functionalized mesoporous silica nanoparticles was studied in relation to the biodegradation behavior of the nanocarrier, with the purpose of determining the dominant release mechanism for the studied drug delivery system. To be able to follow the real-time intracellular release, a hydrophobic fluorescent dye was used as model drug molecule. The in vitro release of the dye was investigated under varying conditions in terms of pH, polarity, protein and lipid content, presence of hydrophobic structures and ultimately, in live cancer cells. Results of investigating the drug delivery system show that the degradation and drug release mechanisms display a clear interdependency in simple aqueous solvents. In pure aqueous media, the cargo release was primarily dependent on the degradation of the nanocarrier, while in complex media, mimicking intracellular conditions, the physicochemical properties of the cargo molecule itself and its interaction with the carrier and/or surrounding media were found to be the main release-governing factors. Since the material degradation was retarded upon loading with hydrophobic guest molecules, the cargo could be efficiently delivered into live cancer cells and released intracellularly without pronounced premature release under extracellular conditions. From a rational design point of view, pinpointing the interdependency between these two processes can be of paramount importance considering future applications and fundamental understanding of the drug delivery system.

Frontispiece: Multicompartmental Microcapsules with Orthogonal Programmable Two‐Way Sequencing of Hydrophobic and Hydrophilic Cargo Release

Frontispiece: Multicompartmental Microcapsules with Orthogonal Programmable Two‐Way Sequencing of Hydrophobic and Hydrophilic Cargo Release

Frontispiz: Multicompartmental Microcapsules with Orthogonal Programmable Two‐Way Sequencing of Hydrophobic and Hydrophilic Cargo Release

Frontispiz: Multicompartmental Microcapsules with Orthogonal Programmable Two‐Way Sequencing of Hydrophobic and Hydrophilic Cargo Release

Multicompartmental Microcapsules with Orthogonal Programmable Two-Way Sequencing of Hydrophobic and Hydrophilic Cargo Release.

Multicompartmental responsive microstructures with the capability for the pre-programmed sequential release of multiple target molecules of opposite solubility (hydrophobic and hydrophilic) in a controlled manner have been fabricated. Star block copolymers with dual-responsive blocks (temperature for poly(N-isopropylacrylamide) chains and pH for poly(acrylic acid) and poly(2-vinylpyridine) arms) and unimolecular micellar structures serve as nanocarriers for hydrophobic molecules in the microcapsule shell. The interior of the microcapsule can be loaded with water-soluble hydrophilic macromolecules. For these dual-loaded microcapsules, a programmable and sequential release of hydrophobic and hydrophilic molecules from the shell and core, respectively, can be triggered independently by temperature and pH variations. These stimuli affect the hydrophobicity and chain conformation of the star block copolymers to initiate out-of-shell release (elevated temperature), or change the overall star conformation and interlayer interactions to trigger increased permeability of the shell and out-of-core release (pH). Reversing stimulus order completely alters the release process.

Multicompartmental Microcapsules with Orthogonal Programmable Two‐Way Sequencing of Hydrophobic and Hydrophilic Cargo Release

AbstractMulticompartmental responsive microstructures with the capability for the pre‐programmed sequential release of multiple target molecules of opposite solubility (hydrophobic and hydrophilic) in a controlled manner have been fabricated. Star block copolymers with dual‐responsive blocks (temperature for poly(N‐isopropylacrylamide) chains and pH for poly(acrylic acid) and poly(2‐vinylpyridine) arms) and unimolecular micellar structures serve as nanocarriers for hydrophobic molecules in the microcapsule shell. The interior of the microcapsule can be loaded with water‐soluble hydrophilic macromolecules. For these dual‐loaded microcapsules, a programmable and sequential release of hydrophobic and hydrophilic molecules from the shell and core, respectively, can be triggered independently by temperature and pH variations. These stimuli affect the hydrophobicity and chain conformation of the star block copolymers to initiate out‐of‐shell release (elevated temperature), or change the overall star conformation and interlayer interactions to trigger increased permeability of the shell and out‐of‐core release (pH). Reversing stimulus order completely alters the release process.

Lipid Raft-Mediated Membrane Tethering and Delivery of Hydrophobic Cargos from Liquid Crystal-Based Nanocarriers.

A main goal of bionanotechnology and nanoparticle (NP)-mediated drug delivery (NMDD) continues to be the development of novel biomaterials that can controllably modulate the activity of the NP-associated therapeutic cargo. One of the desired subcellular locations for targeted delivery in NMDD is the plasma membrane. However, the controlled delivery of hydrophobic cargos to the membrane bilayer poses significant challenges including cargo precipitation and lack of specificity. Here, we employ a liquid crystal NP (LCNP)-based delivery system for the controlled partitioning of a model dye cargo from within the NP core into the plasma membrane bilayer. During synthesis of the NPs, the water-insoluble model dye cargo, 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO), was efficiently incorporated into the hydrophobic LCNP core as confirmed by multiple spectroscopic analyses. Conjugation of a PEGylated cholesterol derivative to the NP surface (DiO-LCNP-PEG-Chol) facilitated the localization of the dye-loaded NPs to lipid raft microdomains in the plasma membrane in HEK 293T/17 cell. Analysis of DiO cellular internalization kinetics revealed that when delivered as a LCNP-PEG-Chol NP, the half-life of DiO membrane residence time (30 min) was twice that of free DiO (DiO(free)) (15 min) delivered from bulk solution. Time-resolved laser scanning confocal microscopy was employed to visualize the passive efflux of DiO from the LCNP core and its insertion into the plasma membrane bilayer as confirmed by Förster resonance energy transfer (FRET) imaging. Finally, the delivery of DiO as a LCNP-PEG-Chol complex resulted in the attenuation of its cytotoxicity; the NP form of DiO exhibited ∼30-40% less toxicity compared to DiO(free). Our data demonstrate the utility of the LCNP platform as an efficient vehicle for the combined membrane-targeted delivery and physicochemical modulation of molecular cargos using lipid raft-mediated tethering.

Triple Emulsion Drops with An Ultrathin Water Layer: High Encapsulation Efficiency and Enhanced Cargo Retention in Microcapsules.

Triple emulsion drops with an ultrathin water layer are developed to achieve high encapsulation efficiency of hydrophobic cargo in a hydrophobic polymeric shell, directly dispersed in water. Furthermore, enhanced retention of volatile hydrophobic cargo is achieved by forming a hydrogel network within this water layer that serves as a physical barrier.

Stimuli-Responsive Codelivery of Oligonucleotides and Drugs by Self-Assembled Peptide Nanoparticles.

Ever more emerging combined treatments exploiting synergistic effects of drug combinations demand smart, responsive codelivery carriers to reveal their full potential. In this study, a multifunctional stimuli-responsive amphiphilic peptide was designed and synthesized to self-assemble into nanoparticles capable of co-bearing and -releasing hydrophobic drugs and antisense oligonucleotides for combined therapies. The rational design was based on a hydrophobic l-tryptophan-d-leucine repeating unit derived from a truncated sequence of gramicidin A (gT), to entrap hydrophobic cargo, which is combined with a hydrophilic moiety of histidines to provide electrostatic affinity to nucleotides. Stimuli-responsiveness was implemented by linking the hydrophobic and hydrophilic sequence through an artificial amino acid bearing a disulfide functional group (H3SSgT). Stimuli-responsive peptides self-assembled in spherical nanoparticles in sizes (100-200 nm) generally considered as preferable for drug delivery applications. Responsive peptide nanoparticles revealed notable nucleotide condensing abilities while maintaining the ability to load hydrophobic cargo. The disulfide cleavage site introduced in the peptide sequence induced responsiveness to physiological concentrations of reducing agent, serving to release the incorporated molecules. Furthermore, the peptide nanoparticles, singly loaded or coloaded with boron-dipyrromethene (BODIPY) and/or antisense oligonucleotides, were efficiently taken up by cells. Such amphiphilic peptides that led to noncytotoxic, reduction-responsive nanoparticles capable of codelivering hydrophobic and nucleic acid payloads simultaneously provide potential toward combined treatment strategies to exploit synergistic effects.

Two-Dimensional, pH-Responsive Oligoglycine-Based Nanocarriers.

The nanocarrier capabilities of atomically smooth two-dimensional sheets of a biantennary oligoglycine peptide C8H16(-CH2-NH-Gly5)2 (also called tectomers) are demonstrated. We show that the pH-controlled, rapid, and reversible assembly and disassembly of oligoglycine can be effectively used for controlled loading and release of the anticancer drug and fluorescent probe coralyne. The calculated partition coefficient in water is of the same order of magnitude or higher when compared to other nanocarriers such as liposomes and micelles, signifying the tectomer's impressive loading capabilities. Moreover, the loading of guest molecules in tectomers facilitates the protection from rapid photochemically induced degradation. Such efficient, pH-sensitive, stable, and biocompatible nanocarriers are extremely attractive for biosensing, therapeutic, and theranostic applications. Additionally, our results suggest that these planar self-assembled materials can also act as phase-transfer vehicles for hydrophobic cargoes further broadening their biomedical and technological applications.

Injectable and degradable, hydrophobically modified poly(oligoethylene glycol methacrylate) hydrogels with decoupled physicochemical and biological properties

Event Abstract Back to Event Injectable and degradable, hydrophobically modified poly(oligoethylene glycol methacrylate) hydrogels with decoupled physicochemical and biological properties Emilia Bakaic1, Niels M. Smeets1, Spencer Imbrogno1 and Todd Hoare1 1 McMaster University, Department of Chemical Engineering, Canada Introduction: Poly(ethylene glycol) (PEG)-based hydrogels are attractive biomaterials due to their hydrophilic, non-cytotoxic and non-immunogenic properties[1]. We recently reported on in situ-gelling PEG-analogue hydrogels based on poly(oligoethylene glycol methacrylate) (POEGMA) formed via rapid gelation of hydrazide and aldehyde-functionalized POEGMA oligomers upon mixing that overcome many of the limitations of conventional PEG-based hydrogels while maintaining their favorable properties[2]. By tuning the length of the oligo(ethylene glycol) side chains[3], both PEG-mimetic and thermoresponsive hydrogels can be formed[4]. However, such materials suffer from two main drawbacks: (1) their highly hydrophilic nature limits their potential for hydrophobic drug delivery and (2) their cross-link density and degradation time cannot be decoupled. Herein we report on hydrogels generated based on hydrazide and aldehyde-functionalized copolymers of OEGMA and self-associating oligo(lactic acid) methacrylate (OLA) that address this challenge. Materials and Methods: Hydrazide-functionalized poly(OEGMA-OLA) copolymers (POxOLAm-z) were prepared by free radical copolymerization of OEGMA, OLA, and acrylic acid followed by carbodiimide-mediated coupling of an excess of adipic acid dihydrazide. OEGMA monomer mixtures of 10% n=2 / 90% n=8-9 (PO10) or 100% n=8-9 (PO100) were used, where n is the number of ethylene glycol repeat units in the OEGMA monomers; the former is thermoresponsive while the latter has no phase transition temperature. OLA monomers containing m=4, 8, or 16 lactic acid repeat units were copolymerized at z=0-20 mol% to vary the hydrophobic driving force for OLA self-assembly. Cross-linking was performed using aldehyde-functionalized POEGMA polymers with the same OEGMA monomer ratio (Fig. 1). Results and Discussion: Gelation of OLA-containing oligomers was significantly faster than OEGMA-only oligomers due to the presence of the hydrophobic intrachain interactions. Small angle neutron scattering confirmed the presence of self-assembled nanodomains in OLA-containing hydrogels, and pyrene fluorescence assays confirmed their hydrophobicity. Hydrogels prepared using longer OLA monomers and/or higher OLA monomer concentrations exhibited stronger mechanics but faster degradation (Fig. 2), attributable to higher physical crosslink densities (via increased OLA self-association) effectively competing with hydrazone bond formation. This competitive cross-linking approach represents a new mechanism to decouple gel mechanics and degradability. The swelling behavior of the resulting hydrogels was not significantly affected by OLA comonomers (Fig. 3A), but bovine serum albumin (BSA) adsorption was significantly increased as more OLA (higher z) of longer chain lengths (higher m) was incorporated. Thermoresponsive PO10OLA gels further enhanced BSA uptake (Fig. 3B) while both significantly slowing release kinetics and reducing burst release (Fig 3C). Conclusions: POEGMA hydrogels hydrophobically modified via copolymerization with oligo(lactic acid methacrylate) offer significant potential to decouple otherwise correlated gel properties (for tissue engineering) and tune both the uptake and release of hydrophobic (or hydrophobic-binding) drug cargoes (for controlled release). NSERC CREATE-IDEM (Integrated Development of Extracellular Matrices) Training Program (funding); 20/20: NSERC Ophthalmic Materials Research Network (funding)

Stimulus-Responsive Release from Poly(ferrocenylsilane) Nanocontainers

Redox-responsive poly(ferrocenylsilane) (PFS) is used to construct nanocontainers that can be loaded with hydrophobic cargo by a miniemulsion approach. The resulting structures comprise a solid shell surrounding a liquid oil core and have diameters of approximately 470 nm with a shell thickness of ca. 29 nm. The electrochemical behavior of the ferrocene group is investigated using cyclic voltammetry. Electrochemical oxidation and the thereby caused change of container morphology are shown. Hydrophobic molecules (Nile Red and 2-propylpyiridine) are loaded into the nanocontainers and can be released upon oxidation of the shell material. The oxidation is achieved chemically by the addition of hydrogen peroxide or by the enzymatic oxidation of glucose to release 2-propylpyridine over a period of time.

Stability of niosomes with encapsulated vitamin D3 and ferrous sulfate generated using a novel supercritical carbon dioxide method

Niosomes were prepared using a novel supercritical carbon dioxide based method to simultaneously encapsulate ferrous sulfate and vitamin D3 as hydrophilic and hydrophobic cargo, respectively. Vesicle particle size was determined to be bimodal with peak diameters of 1.44 ± 0.16 μm and 7.21 ± 0.64 μm, with the smaller peak comprising 98.8% of the total niosomal volume. Encapsulation efficiency of ferrous sulfate was 25.1 ± 0.2% and encapsulation efficiency of vitamin D3 was 95.9 ± 1.47%. Physical stability of the produced niosomes was assessed throughout a storage period of 21 days. Niosomes showed good physical stability at 20 °C, but storage at 4 °C showed an initial burst release, indicating possible rupture of the niosomal membrane. The Korsmeyer–Peppas equation was used to model the release of ferrous sulfate over time at both storage temperatures.