Mixed Micelles Research Articles

Thermally Induced Gelling Systems Based on Patchy Polymeric Micelles

AbstractThermogels that exhibit a sol‐gel transition at body temperature represent a promising class of injectable biomaterials for biomedical applications. Thermogels reported thus far are generally composed of amphiphilic block copolymer micelles with an isotropic thermosensitive surface that induces intermicellar aggregation upon heating. Despite the promise, these hydrogels exhibit low mechanical strengths due to their uncontrollable aggregation resulting in void formation. To gain better control over intermicellar assembly, herein a novel thermogel design concept is presented based on patchy polymeric micelles bearing multiple thermosensitive surface domains. These domains serve as “patches” to bridge the micelles to form a percolated network structure. Patchy micelles are prepared from a binary mixture of amphiphilic block copolymers: Poly(N‐acryloylmorpholine)‐b‐poly(N‐benzylacrylamide) (PAM‐PBzAM) and poly (N‐isopropyl acrylamide)‐b‐poly(N‐benzylacrylamide) (PNIPAM‐PBzAM), where PBzAM, PAM and PNIPAM are the hydrophobic, hydrophilic and thermosensitive blocks, respectively. At 25 °C, the polymers self‐assembled into mixed shell micelles having a phase‐separated shell with PAM‐ and PNIPAM‐rich domains. At 37 °C, the PNIPAM domains undergo a hydrophilic‐to‐hydrophobic transition to induce intermicellar assembly into entangled worm‐like structures resulting in hydrogel formation. Patchy micelles form a homogeneous network structure without voids. The micelle design significantly affects the inter‐micellar assembly, the thermogelling behavior, and the mechanical properties of the hydrogels.

Charge-Stabilized Nanodiscs as a New Class of Lipid Nanoparticles.

Nanoparticles have the potential to improve disease treatment and diagnosis due to their ability to incorporate drugs, alter pharmacokinetics, and enable tissue targeting. While considerable effort is placed on developing spherical lipid-based nanocarriers, recent evidence suggests that high aspect ratio lipid nanocarriers can exhibit enhanced disease site targeting and altered cellular interactions. However, the assembly of lipid-based nanoparticles into non-spherical morphologies has typically required incorporating additional agents such as synthetic polymers, proteins, lipid-polymer conjugates, or detergents. Here, charged lipid headgroups are used to generate stable discoidal lipid nanoparticles from mixed micelles, which are termed charge-stabilized nanodiscs (CNDs). The ability to generate CNDs in buffers with physiological ionic strength is restricted to lipids with more than one anionic group, whereas monovalent lipids only generate small nanoliposomal assemblies. In mice, the smaller size and anisotropic shape of CNDs promote higher accumulation in subcutaneous tumors than spherical liposomes. Further, the surface chemistry of CNDs can be modified via layer-by-layer (LbL) assembly to improve their tumor-targeting properties over state-of-the-art LbL-liposomes when tested using a metastatic model of ovarian cancer. The application of charge-mediated anisotropy in lipid-based assemblies can aid in the future design of biomaterials and cell-membrane mimetic structures.

Next-generation cancer nanotherapeutics: Pluronic® F127 based mixed micelles for enhanced drug delivery.

Cancer, projected to become the second leading cause of mortality globally, underscores the critical need for precise drug delivery systems. Nanotechnology, particularly micelles, has emerged as a promising avenue. These nano-sized colloidal dispersions (< 100 nm) utilize amphiphilic molecules featuring a hydrophilic tail and hydrophobic core, facilitating efficient drug encapsulation and delivery. Pluronic® F127, a triblock copolymer (PEO101-PPO56-PEO101), has emerged as a promising drug carrier due to its non-ionic, less-toxic nature, which prolongs drug circulation time and improves drug delivery across blood-brain and intestinal barriers. Mixed micelles, formed using Pluronic® F127 combined with other polymers, surfactants, and drugs, enhance drug solubility, stability, and targeted delivery. This review highlights the key features of mixed micelles, including enhanced pharmacokinetics and targeting abilities, folic acid (FA) conjugation strategies, superior cytotoxicity with reduced side effects, overcoming multidrug resistance, and versatility across various cancer types and compounds. Additionally, the potential for clinical translation of Pluronic® F127-based mixed micelle in cancer treatment is discussed, addressing current challenges and paving the way for optimized applications.

Study on the synergism mechanism of composite surfactants for oily sludge treatment using microemulsion method

The nonionic surfactant was considered to be the most effective surfactant for the treatment of oily sludge. In this paper, Tween20 and Span80 (T/S) composite surfactant was chosen as emulsifier for the preparation of microemulsion, and their synergistic effect was explored. Clint equation and molecular dynamics simulation was used to interpret the formation of mixed micelles and the results showed that T/S composite surfactant with the mass ratio of 11:1 exhibited the good synergetic effect. Then, the microemulsion prepared using composite surfactants was applied for the treatment of oily sludge. Under the optimal conditions of solid-liquid ratio of 1:1(g: mL), stirring temperature of 40 °C, stirring time of 30 min and stirring speed of 400 rpm, the residual oil rate was reduced to 0.25%, which was much lower than other reported results using chemical methods. Interface tensiometer and quartz crystal microbalance measurement showed that the interfacial tension decreased significantly after the addition of composite surfactant. This work provides a feasible strategy for oily sludge treatment using microemulsion, which promoted the development of oily sludge treatment processes based on microemulsion in practical industry.

Chrysin-loaded Soluplus-TPGS mixed micelles: Optimization, characterization and anticancer activity against hepatocellular carcinoma cell line

Chrysin is a natural flavonoid found in various plants, and it has shown potential therapeutic benefits such as anti-inflammatory, antioxidant, and anticancer properties. However, its clinical application is limited due to poor solubility and low bioavailability. Mixed micelles can help overcome these problems. This study focuses on preparation of Chrysin-loaded mixed micelles with the help of solvent diffusion evaporation method. Soluplus and TPGS were the main components of the formulation, and their proportions were optimized with the help of the central composite design matrix. Thirteen batches were constructed to optimize the mixed micelle formulation based on different Soluplus: Chrysin ratios and TPGS percentages. Response surface methodology and various models were employed to analyze micellar size, size distribution, encapsulation efficiency, and drug loading. The optimized formulation, CHR-MM1, exhibited a particle size of 132.2 ± 7.9 nm, encapsulation efficiency of 98.01 ± 2.27 %, and a zeta potential of −2.10 mV. TEM images revealed that the micelles were spherical in shape. Characterization studies, including FTIR and X-ray diffraction, confirmed the successful encapsulation of Chrysin in an amorphous form within the mixed micelles. The in vitro release studies demonstrated a sustained release behavior in both acidic and neutral pH conditions. The Korsmeyer-Peppas model best described the drug release kinetics. Cellular uptake studies using fluorescence microscopy revealed enhanced internalization of the mixed micelles into Hep G2 cells. Moreover, MTT assays indicated a concentration- and time-dependent cytotoxicity of Chrysin-loaded mixed micelles against Hep G2 cells, outperforming free Chrysin. The flow cytometry analysis results suggested an enhanced apoptotic activity of Chrysin in the mixed micelles as compared to free drug. This study provides a promising strategy for improving the solubility, cellular uptake, and cytotoxicity of Chrysin. Therefore, our results point to the potential of Chrysin-loaded mixed micelles to serve as a therapeutic option for hepatocellular carcinoma.

Polypiperazine-Based Micelles of Mixed Composition for Gene Delivery.

We introduce a novel concept in nucleic acid delivery based on the use of mixed polymeric micelles (MPMs) as platforms for the preparation of micelleplexes with DNA. MPMs were prepared by the co-assembly of a cationic copolymer, poly(1-(4-methylpiperazin-1-yl)-propenone)-b-poly(d,l-lactide), and nonionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) block copolymers. We hypothesize that by introducing nonionic entities incorporated into the mixed co-assembled structures, the mode and strength of DNA binding and DNA accessibility and release could be modulated. The systems were characterized in terms of size, surface potential, buffering capacity, and binding ability to investigate the influence of composition, in particular, the poly(ethylene oxide) chain length on the properties and structure of the MPMs. Endo-lysosomal conditions were simulated to follow the changes in fundamental parameters and behavior of the micelleplexes. The results were interpreted as reflecting the specific structure and composition of the corona and localization of DNA in the corona, predetermined by the poly(ethylene oxide) chain length. A favorable effect of the introduction of the nonionic block copolymer component in the MPMs and micelleplexes thereof was the enhancement of biocompatibility. The slight reduction of the transfection efficiency of the MPM-based micelleplexes compared to that of the single-component polymer micelles was attributed to the premature release of DNA from the MPM-based micelleplexes in the endo-lysosomal compartments.

Multiple activities of sphingomyelin synthase 2 generate saturated fatty acid- and/or monounsaturated fatty acid-containing diacylglycerol

Phosphatidylcholine (PC)-specific phospholipase C (PC-PLC) (EC 3.1.4.3) and phosphatidylethanolamine (PE)-specific PLC (PE-PLC) (EC 3.1.4.62), which generate diacylglycerol (DG) and are tricyclodecan-9-yl-xanthogenate (D609)-sensitive, were detected in detergent-insoluble fractions of mammalian tissues approximately 70 and 35 years ago, respectively. However, the genes and proteins involved in PC-PLC and PE-PLC activities remain unknown. In a recent study, we observed that mammalian sphingomyelin synthase (SMS) 1 and SMS-related protein (SMSr) display PC-PLC and PE-PLC activities in vitro. In the present study, we showed that human SMS2, which is located in detergent-insoluble fractions of the plasma membrane, also possesses PC-PLC activity (approximately 41% of SMS activity), PE-PLC activity (approximately 4%), ceramide phosphoethanolamine synthase (CPES) activity (approximately 46%), and SMS activity in the presence of phospholipid-detergent mixed micelles. Moreover, purified SMS2 reconstituted in detergent-free proteoliposomes (near-native environments) showed PC-PLC, PE-PLC, and CPES activities. Notably, in the presence of approximately 2 mol% ceramide and 4 mol% PC (1:2 ratio), PC-PLC activity was almost equal to SMS activity. SMS2 as PC/PE-PLC showed substrate selectivity for saturated fatty acid- and/or monounsaturated fatty acid-containing PC and PE species. The PC-PLC/SMS inhibitor D609 inhibited all enzyme activities (SMS, PC-PLC, PE-PLC, and CPES) of SMS2. Moreover, Zn2+ strongly inhibited all the enzymatic activities of SMS2. Interestingly, DG inhibited the SMS activity of SMS2 (feedback control). These results indicate that mammalian SMS2 has unique enzymatic properties and is a candidate for a long-sought mammalian PC/PE-PLC.

Parallel (competitive) reactions of micelle formation and cyclodextrin–surfactant inclusion complex formation in aqueous solution: A consequence of the Gibbs–Duhem equation—invariance of the mass action law and the possibility of determining the equilibrium constant of the inclusion complex

The Gibbs–Duhem equation results in the independence between the standard Gibbs free energy of micelle formation and the standard Gibbs free energy of monocomponent surfactant’s and cyclodextrin’s (CD’s) inclusion complex formation in aqueous solution. The experimental data show that the surfactant’s critical micellar concentration increases in the presence of CD. At a constant temperature, the standard Gibbs free energy of micelle formation remains constant, irrespective of the presence of parallel competitive processes such as inclusion complex formation. This indicates that the critical micellar concentration remains unchanged at the corresponding concentration scale. As a result, the equilibrium constant for surfactant–CD inclusion complex formation can be determined by changing the critical micellar concentration in the presence and absence of CD. A graphical method for determining the equilibrium constant of the inclusion complex is also presented. An analytical approach for analyzing the influence of the formation of the inclusion complex with CD on the formation of the binary mixed micellar pseudophase is presented. Suppose that different values exist for the equilibrium constants of the formation of the inclusion complex for two surfactants from their binary mixture. In this case, there is a change in the initial mole fraction from the initial mixture of surfactants, which should be considered when applying the regular solution theory protocol when determining the parameters of a binary mixed micelle in the presence of CD.

Lecithin-based mixed polymeric micelles for activity improvement of curcumin against Staphylococcus aureus

Considering cellular uptake promotion of lecithin and high expression of phospholipase in S. aureus, we designed curcumin (Cur)-loaded soy lecithin-based mPEG-PVL copolymer micelles (MPPC). The effect of soy lecithin on the anti-S. aureus activity of the formulation was studied with cur-loaded mPEG-PVL micelles (MPC without soy lecithin) as control. It was found that MPPC enhanced the water-solubility of Cur, and showed slow and sustained release behavior of Cur. Although MPPC had the same anti-S. aureus activity as Cur, its activity was significantly higher than MPC due to the cellular uptake promotion of soybean lecithin. It was noted that MPPC had good inhibition or destruction effect on biofilm, significant cell membrane damage, strong inhibition effect on protease or lipase production, and obvious induction effect on ROS expression when compared with Cur and MPC. So, the introduction of soy lecithin could improve the antibacterial activity of Cur. The lecithin-based micelles would offer potential to deliver antibacterial drugs for improved therapeutic action.

Construction and Properties Evaluation of the Binary Flooding System Based on Lipid Peptide.

To enhance crude oil recovery under complex reservoir conditions and reduce the environmental impact of the oil displacement system, a biosurfactant lipid peptide (TH) was combined with four chemical surfactants. From these combinations, those capable of achieving an ultralow interfacial tension region (<10-2 mN/m) were selected. The selected surfactant mixtures were then combined with polyacrylamide (HPAM) to construct a surfactant-polymer binary oil displacement system. The results showed that TH/OAB(2:1), TH/OAB(3:1), and TH/EAO(3:1) could reduce IFT to the ultralow interfacial tension region. Compound surfactants are easier to form mixed micelles than single surfactants, and the EACN of TH/OAB(2:1) and TH/EAO(3:1) is consistent with EACNOil, which can achieve higher surface activity at lower concentrations. The three compound surfactants have a wide range of ultralow interfacial tension concentrations and excellent antidilution performance. TH/OAB(2:1) and TH/EAO(3:1) have better antiformation adsorption performance than TH/OAB(3:1), and the oil washing rate of TH/OAB(2:1) is up to 80.30%. TH and OAB have spatial complementarity, which can increase the molecular packing density at the oil-water interface and reduce the IFT. In CaCl2 and NaCl solutions, the IFT of the two binary flooding systems constructed by TH/OAB(2:1) and TH/EAO(3:1) and HPAM remained in the ultralow interfacial tension region, with excellent salt resistance. When aged in the reservoir for 90 days, the IFT slightly increased but the viscosity decreased significantly. Adding a viscosity retaining agent (JW) was required to maintain the viscosity of the system. In the simulated oil displacement experiment, the recovery improvement of the two binary oil displacement systems was higher than those of surfactant and polymer alone. This study provides a new idea for the alkali-free surfactant-polymer binary oil flooding system and provides theoretical support for the practical application of TH in tertiary oil recovery.

The conformational equilibria of a human GPCR compared between lipid vesicles and aqueous solutions by integrative 19F-NMR.

Endogenous phospholipids influence the conformational equilibria of G protein-coupled receptors, regulating their ability to bind drugs and form signaling complexes. However, most studies of GPCR-lipid interactions have been carried out in mixed micelles or lipid nanodiscs. Though useful, these membrane mimetics do not fully replicate the physical properties of native cellular membranes associated with large assemblies of lipids. We investigated the conformational equilibria of the human A2A adenosine receptor (A2AAR) in phospholipid vesicles using 19F solid-state magic angle spinning NMR (SSNMR). By applying an optimized sample preparation workflow and experimental conditions, we were able to obtain 19F-SSNMR spectra for both antagonist- and agonist-bound complexes with sensitivity and linewidths closely comparable to those achieved using solution NMR. This facilitated a direct comparison of the A2AAR conformational equilibria across detergent micelle, lipid nanodisc, and lipid vesicle preparations. While antagonist-bound A2AAR showed a similar conformational equilibria across all membrane and membrane mimetic systems, the conformational equilibria of agonist-bound A2AAR exhibited differences among different environments. This suggests that the conformational equilibria of GPCRs may be influenced not only by specific receptor-lipid interactions but also by the membrane properties found in larger lipid assemblies.

Novel Delivery Systems of Raloxifene Hydrochloride for Improved Bioavailability and Therapeutic Efficacy: A Review

Raloxifene hydrochloride belongs to the selective estrogen receptor modulator category. Initially, US FDA approved its use for the prevention and treatment of osteoporosis in postmenopausal women. Later, raloxifene hydrochloride was also approved for the prevention of invasive breast carcinoma in post-menopausal women under the high-risk category. Despite its immense and diverse therapeutic potential, the oral bioavailability of raloxifene hydrochloride is only ~ 2%. The factors responsible for the poor bioavailability of raloxifene hydrochloride include its amphiphobic nature, para-glycoprotein pump-mediated efflux in the intestine, and high pre-systemic glucuronidation. In the past two decades, multiple novel delivery systems, viz. lipid-based nanocarriers, polymeric nanoparticles, polymer-lipid hybrid nanoparticles, micelles, and mixed micelles, have been developed to overcome its drawbacks. Moreover, inclusion complex, phospholipid complex, and solid dispersion have also been developed to improve its solubility and dissolution rate. Further, some research groups successfully explored non-peroral routes like nasal and transdermal for augmenting the raloxifene hydrochloride bioavailability and its therapeutic efficacy. Hence, the principal objective of this review paper is to critically analyze all the delivery systems developed for raloxifene hydrochloride with their advantages and limitations. In addition, a detailed discussion of the physicochemical and pharmacokinetic parameters of raloxifene hydrochloride has been included in this paper. An in-depth understanding of these parameters will assist formulation scientists in developing efficient delivery systems in the future. In conclusion, the literature review revealed that the nanoparticulate systems successfully augmented the raloxifene hydrochloride bioavailability and therapeutic efficacy in pre-clinical experiments. However, future clinical trials should be conducted to assess their safety and therapeutic efficacy for rapid preclinical to clinical translation.

Effect of biosurfactants on the self-assembly behavior and drug encapsulation for branched block copolymers

For the past few years, block copolymers have attracted extensive attention in the field of drug delivery. In this work, the hyperbranched PEO-PPO block copolymer H1304 having the same PEO segments and PPO segments as the commercially available 4-branched block copolymer Tetronic1304 was synthesized. Compared with T1304, H1304 was characterized by lower cloud point, smaller critical micelle concentration (CMC), larger micellar size and better drug solubilization capacity. The effect of three biosurfactants lecithin (PC), alkyl glycogen (APG), sodium deoxycholate (NaDC) on the aggregation behavior of H1304 and T1304 were researched. Meanwhile, the solubilization and in vitro release properties of hydrophobic anticancer drug podophyllotoxin were also evaluated. The addition of PC or APG to form a mixed micelle reduced the cloud point and CMC, optimized the drug carrier characteristics. NaDC exhibited different effects due to its unique disclike surface structure. NaDC formed back-to-back aggregates, which interfered the self-assembly process of block copolymer and in turn caused variation of the copolymer micellar properties. The study of mixed systems consisting of biosurfactants and block copolymers will help to change the performance of copolymers in various pharmaceutical fields and contribute to the application of copolymers as drug carriers in drug delivery systems.

Bioavailability enhancement of atazanavir sulphate using mixed micelles: in vitro characterization and in vivo pharmacokinetic study.

This study aims to enhance the oral bioavailability of atazanavir sulphate, a human immunodeficiency virus-1 protease inhibitor known for its poor oral absorption, by formulating mixed micelles using Soluplus® and Kolliphor HS 15. Mixed micelles were prepared through the thin film hydration technique. The micelles were characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, drug loading, and confirmed for atazanavir sulphate encapsulation via FTIR studies. In vitro release studies were conducted, and the morphology of the micelles was examined using TEM. Atazanavir sulphate mixed micelles exhibited a particle size of 62.92nm, PDI of 0.221, zeta potential of - 17.8mV, high entrapment efficiency (99.76 ± 1.06), and drug loading (14 ± 0.82). In vitro release studies demonstrated sustained release up to 12h, with maximum solubility observed at 2h under pH 1.2 conditions. TEM analysis revealed spherical micelle morphology. Oral administration of atazanavir sulphate mixed micelles showed a 1.23-fold increase in relative bioavailability compared to pure drug suspension. The formulation of mixed micelles using Soluplus® and Kolliphor HS 15 offers a promising strategy to improve the oral bioavailability of atazanavir sulphate. These findings suggest the potential utility of mixed micelles as an effective delivery system for atazanavir sulphate, offering enhanced therapeutic outcomes for patients.

Optimization and Appraisal of Nintedanib-Loaded Mixed Polymeric Micelles as a Potential Nanovector for Non-Invasive Pulmonary Fibrosis Mitigation.

Nintedanib (NTD), a triple tyrosine kinase receptor inhibitor, is the recommended first-line tackling option for idiopathic pulmonary fibrosis (IPF). Nevertheless, the adequacy of NTD is curtailed by issues associated with its low solubility, first-pass effect, poor bioavailability, and liver toxicity. The objective of our work was to develop a non-invasive intratracheal (i.t.) nanoparadigm based on NTD-loaded polymeric mixed micelles (NTD-PMMs) that can effectively treat IPF by sustaining the release of NTD, and snowballing its bioavailability, solubility, and efficacy. Design-Expert® software was used to optimize various NTD-PMMs formulations via Box-Behnken design adopting the thin-film hydration technique. The optimum formulation was chosen and in vivo tested in a rat model to explore its comparative bioavailability and toxicity. The formulation composition with 309.217 mg of Soluplus, 150 mg of Tween 80, and 40 mg of sodium deoxycholate was found to fulfill the requisites of an optimum NTD-PMMs formulation. The optimum NTD-PMMs formulation divulged 90.26% entrapment efficiency with a surface charge of -14.72 mV and a nanoscale diameter of 61.36 nm. Also, it substantially sustained the release of NTD by 66.84% after 24 h and manifested a pronounced stability. In vivo histopathology investigations verified the safety of NTD-PMMs delivered intratracheally. Moreover, pharmacokinetic analyses disclosed accentuated relative bioavailability of the optimized NTD-PMMs by 2.4- and 3.82-fold as compared with both the i.t. and oral crude NTD suspensions, respectively. Overall, the current results elicited the potential of PMMs to serve as a promising pulmonary nanovector for the targeted delivery of NTD.

Investigation the binding and partition properties of azithromycin drug using drug-surfactant mixed micelles in the presence of trisodium citrate electrolyte

The significance of mixed micelle in pharmaceutical industries is improving the binding and solubility of poorly water-soluble drugs. This work highlighted the effect of organic counterion (NAC) for improving the micellization association of zwitterionic (CAPB) and cationic drug (DPC) by surface tension measurements. The Corrin–Harkins (CH) approach assessed the CAPB, DPC and CAPB-DPC counterion binding values for DPC in the aqueous and NAC media at 25 °C. The counterion binding B for CAPB-DPC from αDPC 1.0–0.0 was found 0.536, 0.3801, 0.368, 0.355, 0.310 and 0.272 in the presence of NAC which indicated that DPC improved the counterion binding in the mixed micellar system. The Gibb’s free energy of micellization (ΔGmic°) were increased and became more negative, suggesting that the CAPB–DPC interaction was controlled by electrostatic interaction. Furthermore, the application of mixed micelle was utilized to enhance the binding constant (LogKb) and partition coefficient (LogKx) of the poorly water-soluble drug (AZI) in aqueous and NAC media at 25 °C using a UV spectrophotometer. From UV spectra, The LogKb and LogKx of AZI were lower in single micellar systems and higher in mixed micellar systems of CAPB-DPC. The maximum LogKb values at αDPC 0.4 were found 3.091, 3.233, 3.417, and 3.368 and LogKx values were found 4.749, 4.919, 5.087 and 5.049 in the presence of 0.0, 0.5, 3.0 and 20 mmol L−1 of NAC. AZI molecules are found in the palisade layer of mixed micelle when the DPC mole fraction is less than αDPC 0.6, while more than αDPC 0.6 causes steric hindrance, increasing hydrophobicity in the system. Furthermore, surfactant-drug mixed micelles could serve as poorly drug-solubilizing agents, as well as a multidrug delivery system in pharmaceutical applications.

Soluplus-TPGS Mixed Micelles as a Delivery System for Brigatinib: Characterization and In Vitro Evaluation.

Lung cancer is a major public health concern, with a high incidence and fatality rate. Its treatment is very difficult, as it is mostly diagnosed in advanced stages. Non-small cell lung carcinoma (NSCLC) is the major form of lung carcinoma that persists. Brigatinib (BGT), a powerful small-molecule tyrosine kinase inhibitor, has demonstrated significant therapeutic potential in the treatment of NSCLC with anaplastic lymphoma kinase (ALK) mutations. However, the therapeutic applicability of BGT is hampered by its low solubility and bioavailability. In this study, we developed a mixed micelle system comprising Soluplus and TPGS loaded with BGT. BGT was encapsulated into the mixed micelles using various combinations of Soluplus and TPGS, with encapsulation efficiency (EE%) ranging from 52.43 ± 1.07 to 97.88 ± 2.25%. The dynamic light scattering data showed that the mixed micelles ranged in size from 75.7 ± 0.46 to 204.3 ± 5.40 nm. The selected mixed micelles (F6) showed approximately 38% BGT release in the first 2 h, and subsequently, within 72 h, the release was 94.50 ± 5.90%. The NMR experiment confirmed the formation of micelles. Additionally, the mixed micelles showed significantly higher cellular uptake (p < 0.05) and increased cytotoxicity (p < 0.05) as compared to the free BGT. Specifically, the obtained IC50 values for BGT-loaded Soluplus-TPGS mixed micelles and free BGT were 22.59 ± 6.07 and 61.45 ± 6.35 μg/mL, respectively. The results of the in vitro stability experiment showed that the selected mixed micelle (F6) was stable at both room temperature and 4 °C, with only minor changes in size and PDI. Our results indicate great potential for the developed Soluplus-TPGS mixed micelles as a delivery system for BGT.

Assessing the Interaction between Dodecylphosphocholine and Dodecylmaltoside Mixed Micelles as Drug Carriers with Lipid Membrane: A Coarse-Grained Molecular Dynamics Simulation.

Integrating drugs into cellular membranes efficiently is a significant challenge in drug delivery systems. This study aimed to overcome these barriers by utilizing mixed micelles to enhance drug incorporation into cell membranes. We employed coarse-grained molecular dynamics (MD) simulations to investigate the stability and efficacy of micelles composed of dodecylphosphocholine (DPC), a zwitterionic surfactant, and dodecylmaltoside (DDM), a nonionic surfactant, at various mixing ratios. Additionally, we examined the incorporation of a mutated form of Indolicidin (IND) (CP10A), an anti-HIV peptide, into these micelles. This study provides valuable insights for the development of more effective drug delivery systems by optimizing the mixing ratios of DPC and DDM. By balancing stability and penetration efficiency, these mixed micelles can improve the delivery of drugs that face challenges crossing lipid membranes. Such advancements can enhance the efficacy of treatments for various conditions, including viral infections and cancer, by ensuring that therapeutic agents reach their intended cellular targets more effectively.

High efficacy of chloroquine-derived bile salts in Pluronic F127 micelles against blood-stage Plasmodium falciparum

Colloidal nanocarriers can play a key role in the efficacious delivery of drugs, including antimalarials. Here, we investigated the ability of polymeric micelles of the block copolymer F127 to act as nanovehicles for two organic salts derived from chloroquine and human bile acids, namely, chloroquinium cholate (iCQP1) and chloroquinium glycocholate (iCQP1g). We have previously reported the strong in vitro antiplasmodial activity of these salts, which displayed IC50 values of 13 and 15 nM against blood forms of Plasmodium falciparum, respectively. By deriving from amphiphilic lipids, iCQP1 and iCQP1g also enclose the ability to act as surface-active ionic liquids (SAILs). The micellization properties of neat F127 and of the F127/SAIL mixtures were initially investigated to gain physicochemical insight into the interaction between polymer and bioactive SAILs, resorting to differential scanning calorimetry, surface tension measurements and dynamic light scattering. Micelle formation by F127 is an endothermic process strongly temperature and concentration dependent. Interestingly, this process is significantly changed when the molar fraction of SAIL (xSAIL) in the F127/SAIL mixture is varied between 0.33 and 0.90. Both SAILs favor the formation of mixed micelles by decreasing the micellization temperature, and (observed only when for xSAIL = 0.33) by synergistically decreasing the cmc. Concomitantly, the micellar size is reduced from 18 to 13 nm as xSAIL is increased from 0.33 to 0.90. Crucially, in vitro assays show that when the SAILs are loaded into F127 polymeric micelles, their antiplasmodial efficacy is substantially enhanced, with a significant drop in IC50, especially for the iCQP1/F127 system. This opens new possibilities for the nanoformulations of antimalarial compounds.

Effect of lipid type on betulin-stabilized water-in-oil Pickering emulsion: emulsion properties, in vitro digestion, and betulin bioaccessibility.

The Pickering emulsion delivery technique is widely acknowledged for its efficacy in serving as a carrier that can encapsulate functional components effectively. Previous studies have shown significant differences in the stability of Pickering emulsions composed of different oil phases and in the bioaccessibility of the encapsulated functional ingredients. This study therefore investigated the effects of different carrier oils in the betulin self-stabilized water-in-oil (W/O) Pickering emulsion on the stability of the emulsion and bioaccessibility of betulin. The results showed that the oil type was one of the main factors affecting the stability of the emulsion. Palm oil and coconut oil provided better storage stability and centrifugal stability due to the high saturated fatty acid content. The bioavailability of betulin correlated significantly with the composition and characteristics of fatty acids in carrier oils. Carrier oils rich in low-saturation long-chain fatty acids tended to release more free fatty acids (FFAs), thus forming larger and more mixed micelles with stronger swelling and dissolution ability, resulting in a relatively high bioaccessibility of betulin. In contrast, the bioaccessibility of betulin in the emulsion prepared by coconut oil (with high saturated fatty acid content) was relatively low (1.17%). The results of this study indicate that selecting an appropriate carrier oil is important for the design of self-stabilized W/O Pickering emulsions to improve the bioaccessibility of betulin and other lipophilic bioactivities effectively. © 2024 Society of Chemical Industry.