Cationic Micelles Research Articles

Supramolecular Bioconjugation Strategy for Antibody-Targeted Delivery of siRNA.

RNA interference is a widely used biological process by which double-stranded RNA induces sequence-specific gene silencing by targeting mRNA for degradation. However, the physicochemical properties of siRNAs make their delivery extremely challenging, thus limiting their bioavailability at the target site. In this context, we developed a versatile and selective siRNA delivery system of a trastuzumab-conjugated nanocarrier. These immunoconjugates consist of the assembly by electrostatic interactions of an oligonucleotide-modified antibody with a cationic micelle for the targeted delivery of siRNA in HER2-overexpressing cancer cells. Results show that, when associated with the corresponding siRNA at the appropriate N/P ratio, our supramolecular assembly was able to efficiently induce luciferase and PLK-1 gene silencing in a cell-selective manner in vitro.

Nanosized Complexes of the Proteolytic Enzyme Serratiopeptidase with Cationic Block Copolymer Micelles Enhance the Proliferation and Migration of Human Cells.

In this study, we describe the preparation of the cationic block copolymer nanocarriers of the proteolytic enzyme serratiopeptidase (SER). Firstly, an amphiphilic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA9-b-PCL35-b-PDMAEMA9) triblock copolymer was synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization. Then, cationic micellar nanocarriers consisting of a PCL hydrophobic core and a PDMAEMA hydrophilic shell were formed by the solvent evaporation method. SER was loaded into the polymeric micelles by electrostatic interaction between the positively charged micellar shell and the negatively charged enzyme molecules. The particle size, zeta potential, and colloid stability of complexes as a function of SER concentration were investigated by dynamic and electrophoretic light scattering. It was found that SER retained its proteolytic activity after immobilization in polymeric carriers. Moreover, the complexes have a concentration-dependent enhancing effect on the proliferation and migration of human keratinocyte HaCaT and gingival fibroblast HGF cells.

The Role of Surfactant Head Group Charge on Binding of Hoechst 33258 with Micelles

AbstractOwing to the diverse biological application, photophysical behaviour of Hoechst 33258 (H33258) is an important topic in biophysical research. Here, we have reported the photophysical behavior of H33258 in model biomembrane mimicking micellar microenvironment. In order to understand the molecular mechanism of the interaction of H33258 with micelles, we have used cationic (Hexadecetyltrimethyl ammonium bromide (CTAB)), anionic (sodium dodecyl sulphate (SDS)), and non‐ionic (t‐octylphenoxypolyoxyethanol, Triton‐X100 (TX 100)) micelles. From the steady‐state emission study the evaluated apparent binding constant (Kb) values for the complex formation between H33258 and CTAB, SDS and TX 100 micelle were (1.45±0.42)×105, (31.95±4.89)×105 and (3.10±0.73)×105 M−1, respectively. Thus, it was found that the Kb value was greater in the case of anionic micelle than non‐ionic and cationic micelles. Such differences in Kb values were due to the electrostatic interaction and hydrogen bond formation between the probe molecule and micelles. In addition, time‐resolved fluorescence decay and time‐resolved fluorescence anisotropy studies were performed to understand the dynamical behavior of H33258 in presence of micelles. The interaction of H33258 with micelles might be useful to study the structure and dynamics of different bio‐membranes and to formulate new drug delivery system.

Crafting Ultra–Sensitive and selective fluorescent probes for CH3Hg+ detection in groundwater: A 3–in–1 strategy

Development of ultra–sensitive and selective fluorescent probes exclusively targeting CH3Hg+, especially against Hg2+, in real ecosystems like groundwater remains a critical yet formidable challenge. In this contribution, we present a series of fluorescent carbazole boronic acids (probes 1–4) designed for the highly sensitive and selective detection of Hg2+ and CH3Hg+ using an innovative 3–in–1 strategy. Notably, probe 4 exhibited exceptional performance in mercury detection in real groundwater, achieving a limit of detection concentration as low as 1.0 ppb for both Hg2+ and CH3Hg+, even in the presence of elevated levels of interfering cations or anions. Subsequently, a new fluorescent probe system was established by embedding probe 4 into cationic micelles, employing a microphase separation protocol. This resulted in exclusive selectivity towards CH3Hg+ over Hg2+ and other interfering ions with sensitivity as low as 10.0 ppb. This advancement not only addresses a critical gap in environmental monitoring but also demonstrates the potential for broader applications of these probes in sensitive detection methodologies.

Cationic surfactant-assisted assembly of water-dispersible MnO2 onto indoor textiles for anti-bacterial and HCHO removal

Nowadays, the applications of nanoparticle-decorated textiles for environmental governmental governance have aroused great concerns, while the poor fastness and uncontrolled aggregation of the nanoparticles negatively influenced its practical use. Herein, an environmental-friendly synthesis strategy of water-dispersible MnO2 was demonstrated by using the reductant of 2-(N-morpholino) ethanesulfonic acid (MES) and template of cetyltrimethylammonium bromide (CTAB), and then the as-prepared MnO2 was further employed as a multifunctional textile coating. In all the procedures under room temperatures, three effects of cationic CTAB micelles were thoroughly explored, from optimizing MnO2 to uniform micro/nanoscale through template strategy, to bridging the gaps between electronegative particles and fabrics, and even providing stable antibacterial effect. Consequently, without any additional binding agents, multifunctional cotton textile was obtained by simply immersing cotton into a MnO2-CTAB aqueous solution, and appeared antibacterial rates (over 99 %) to both E. coli and S. aureus. Meanwhile, HCHO removal and ultraviolet blocking (UVA<0.1 %) properties as well as high durability of the nanoparticles are also introduced to the textiles. We believe as-presented cationic surfactant-templated strategy for regulating synthesis and deposition of functional particles onto cotton textiles has broad application prospects in green and sustainable functionalization of decoration textiles.

Interaction of anionic dye ethyl orange and cationic CnTAC surfactants: A multi technique investigation

This research presents the application of electrical conductivity measurements to ascertain the critical micelle concentration (CMC) values for N-alkyltrimethylammonium chloride surfactants (CnTAC; with alkyl chain lengths of n = 12, 14, 16, and 18). Complementary spectrophotometric analysis was conducted to probe the interactions between CnTAC series and Ethyl Orange (ETO), an anionic dye. Applying the Benesi-Hildebrand and Scott equations, we evaluated the binding constant (Kb) of the cationic micelles’ interaction with ETO, which in turn facilitated calculations of Gibb’s free energy (ΔG°) changes. These calculations provided insight into the binding affinity of ETO to the micelles. Our findings suggest that the interaction between ETO and CnTAC is contingent on the surfactant concentration, with higher concentrations leading to a disassociation of the ETO-CnTAC complex and a reduction in ETO adsorption. Notably, the alkyl chain length within CnTAC molecules critically affects various properties, including ΔG°, CMC, and other thermodynamic parameters that determine the surfactant’s energetic behavior. The study underscores the importance of the alkyl chain length in dictating the interaction dynamics and properties of CnTAC surfactants. A trend was observed where longer alkyl chains lead to increased Kb values and reductions in both CMC and ΔG°, enhancing dye solubilization and interaction spontaneity. The affinity sequence of ETO to the micelles, influenced by alkyl chain length, was found to be C12TAC < C14TAC < C16TAC < C18TAC.

Low molecular weight chitosan based GSH-responsive self-assembled cationic micelle with enhanced anti-tumor effect by combining oxidative damage and chemotherapy

A novel cationic lipoic acid grafted low molecular weight chitosan (LCNE-LA) conjugate was constructed and further self-assembled into GSH-responsive cationic nanocarrier to achieve better antitumor effect by combining encapsulated chemotherapy and oxidative damage induced by ROS. The resultant LCNE-LA cationic micelle exhibited favorable physicochemical properties (low CMC, small size, positively zeta potential and good stability), excellent biosafety and desired redox sensitivity. Next, doxorubicin (Dox) was embedded into hydrophobic core to form stable Dox/LCNE-LA micelle that had superior loading capacity. The GSH-induced release behavior, cellular uptake ability, ROS generation and GSH consumption capacity and in vitro antitumor activity of Dox/LCNE-LA micelle were systematically evaluated. Consequently, Dox/LCNE-LA cationic micelle with positively charged could efficiently enter into cancer cell and redox-sensitive release Dox via disulfide-thiol exchange reaction, which usually expend abundant GSH and disrupt redox homeostasis. Studies further confirmed that Dox/LCNE-LA micelle could increase ROS and reduced GSH content which might cause oxidative damage to tumor cell. Antitumor activity indicated that Dox/LCNE-LA micelle achieved an excellent cancer-killing effect, which might be attributed to combination treatment of Dox and ROS induce oxidative damage. Overall, this research was expected to provide a platform for antitumor treatment by triggering Dox release and promoting ROS generation.

Polymeric micellar nanoparticles for effective CRISPR/Cas9 genome editing in cancer

The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) gene editing has attracted extensive attentions in various fields, however, its clinical application is hindered by the lack of effective and safe delivery system. Herein, we reported a cationic micelle nanoparticle composed of cholesterol-modified branched small molecular PEI (PEI-CHO) and biodegradable PEG-b-polycarbonate block copolymer (PEG-PC), denoted as PEG-PC/PEI-CHO/pCas9, for the CRISPR/Cas9 delivery to realize genomic editing in cancer. Specifically, PEI-CHO condensed pCas9 into nanocomplexes, which were further encapsulated into PEG-PC nanoparticles (PEG-PC/PEI-CHO/pCas9). PEG-PC/PEI-CHO/pCas9 had a PEG shell, protecting DNA from degradation by nucleases. Enhanced cellular uptake of PEG-PC/PEI-CHO/pCas9 nanoparticles was observed as compared to that mediated by Lipo2k/pCas9 nanoparticles, thus leading to significantly elevated transfection efficiency after escaping from endosomes via the proton sponge effect of PEI. In addition, the presence of PEG shell greatly improved biocompatibility, and significantly enhanced the in vivo tumor retention of pCas9 compared to PEI-CHO/pCas9. Notably, apparent downregulation of GFP expression could be achieved both in vitro and in vivo by using PEG-PC/PEI-CHO/pCas9-sgGFP nanoparticles. Furthermore, PEG-PC/PEI-CHO/pCas9-sgMcl1 induced effective apoptosis and tumor suppression in a HeLa tumor xenograft mouse model by downregulating Mcl1 expression. This work may provide an alternative paradigm for the efficient and safe genome editing in cancer.

Conductometric and spectral analyses of dye-surfactant interactions between indigo carmine and N-alkyltrimethylammonium chloride

The electrical conductivity technique was used to investigate the critical micelle concentration (CMC) of cationic surfactants N-alkyltrimethylammonium chloride (CnTAC; n = 12, 14, 16, and 18). Meanwhile, the interaction between CnTAC and indigo carmine (IC, an anionic dye) was studied using spectrophotometry. Employing the Benesi-Hildebrand and Scott equations, the binding constant (Kb) of IC to the cationic micelles was determined. Calculation of the Gibbs free energy (ΔG) revealed the tendency of IC to bind to micelles. The association between IC and CnTAC clearly depends on the CnTAC concentration: a lower surfactant concentration disrupts the IC-CnTAC complex and decreases IC adsorption, while a higher surfactant concentration has the opposite effect. The alkyl chain length of CnTAC was also found to affect the CMC, Kb, and thermodynamic parameters. A longer alkyl chain reduces the CMC and ΔG and increases Kb, leading to increased solubilization and high spontaneity of the dye. The binding of IC to micelles is ranked as C12TAC < C14TAC < C16TAC < C18TAC.

Systemic and Local Administration of a Dual-siRNA Complex Efficiently Inhibits Tumor Growth and Bone Invasion in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral and oropharyngeal cancer cases and is characterized by high mortality and poor prognosis. RNA-based gene therapies have been developed as an emerging option for cancer treatment, but it has not been widely explored in OSCC. In this work, we developed an efficient siRNA cationic micelle DOTAP-mPEG-PCL (DMP) by self-assembling the cationic lipid DOTAP and monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) polymer. We tested the characteristics and transformation efficiency of this micelle and combined DMP with siRNA targeting STAT3 and TGF-β to evaluate the antitumor effect and bone invasion interfering in vitro and in vivo. The average size of the DMP was 28.27 ± 1.62 nm with an average zeta potential of 54.60 ± 0.29 mV. The DMP/siRNA complex showed high delivery efficiency, with rates of 97.47 ± 0.42% for HSC-3. In vitro, the DMP/siSTAT3 complex exhibited an obvious cell growth inhibition effect detected by MTT assay (an average cell viability of 25.1%) and clonogenic assay (an average inhibition rate of 51.9%). Besides, the supernatant from HSC-3 transfected by DMP/siTGF-β complexes was found to interfere with osteoclast differentiation in vitro. Irrespective of local or systemic administration, DMP/siSTAT3+siTGF-β showed antitumor effects and bone invasion inhibition in the OSCC mice mandibular invasion model according to tumor volume assays and Micro-CT scanning. The complex constructed by DMP cationic micelles and siSTAT3+siTGF-β represents a potential RNA-based gene therapy delivery system for OSCC.

ROS-responsive polyprodrug micelles carrying suicide genes in combination with chemotherapy and gene therapy for prostate cancer treatment.

Prostate cancer is the most common malignant tumor in the male reproductive system, and its incidence increases with age. Chemotherapy is one of the main strategies for treating prostate cancer, but it often comes with unavoidable side effects. Nanocarriers can improve drug utilization and targeting, and cationic carriers can also carry nucleic acids for gene therapy. In this study, we prepared a cationic micelle constructed from a polyprodrug that can deliver both chemotherapeutic drugs and nucleic acids simultaneously. The typical chemotherapeutic drug hydroxycamptothecin (HCPT) was linked by reactive oxygen species (ROS)-responsive coupling agents and forms amphiphilic block polymers with low molecular weight polyethyleneimine (PEI). The resulting cationic micelles can be triggered by high levels of ROS in tumor cells and collapse to release HCPT and suicide genes to kill tumor cells. At the same time, it reduces the killing of normal cells. In prostate cancer cells, it has been confirmed that the co-delivery carriers combined with chemotherapy and a suicide gene prodrug system have shown an ideal therapeutic effect on prostate cancer.

Cationic micelles in deep eutectic solvents: effects of solvent composition.

Deep eutectic solvents (DES) are mixtures of hydrogen bond donors and acceptors that form strongly hydrogen-bonded room temperature liquids. Changing the H-bonding components and their ratios can alter the physicochemical properties of deep eutectic solvents. Recent studies have shown p-toluenesulfonic acid (pTSA) forms room temperature liquids with choline chloride (ChCl) at different molar ratios: 1 : 1, 1 : 2 and 2 : 1 [Rodriguez Rodriguez et al., ACS Sustain. Chem. Eng., 2019, 7(4), 3940]. They also showed that the composition affects the physical properties of these liquids and their ability to dissolve metal oxides. In this work we evaluate the solubility and self-assembly of cationic surfactants alkyltrimethyl ammonium bromides (CnTAB) in these pTSA/ChCl based liquids. CnTABs are insoluble in 1pTSA : 2ChCl, whereas in 1pTSA : 1ChCl and 2pTSA : 1ChCl they form micelles. We characterise CnTAB (n = 12, 14, 16) micelles using small angle neutron scattering and also look at interaction of water with the micelles. These studies help determine the interaction of DES components with the surfactant and the influence of varying pTSA and water ratios on these interactions. This provides potential for controlled surfactant templating and for tuning rheology modification in such systems.

Inhibitory effect of doxycycline conjugated with deoxycholic acid and polyethylenimine conjugate on nasal fibroblast differentiation and extracellular production.

Chronic rhinosinusitis (CRS) is an inflammatory disease affecting the sinuses or nose. Persistent inflammatory responses can lead to tissue remodeling, which is a pathological characteristics of CRS. Activation of fibroblasts in the nasal mucosal stroma, differentiation and collagen deposition, and subepithelial fibrosis have been associated with CRS. We aimed to assess the inhibitory effects of doxycycline and deoxycholic acid-polyethyleneimine conjugate (DA3-Doxy) on myofibroblast differentiation and extracellular matrix (ECM) production in nasal fibroblasts stimulated with TGF-β1. To enhance efficacy, we prepared DA3-Doxy using a conjugate of low-molecular-weight polyethyleneimine (PEI) (MW 1800) and deoxycholic acid (DA) and Doxy. The synthesis of the DA3-Doxy polymer was confirmed using nuclear magnetic resonance, and the critical micelle concentration required for cationic micelle formation through self-assembly was determined. Subsequently, the Doxy loading efficiency of DA3 was assessed. The cytotoxicity of Doxy, DA3, PEI, and DA-Doxy in nasal fibroblasts was evaluated using the WST-1 assay. The anti-tissue remodeling and anti-inflammatory effects of DA3-Doxy and DA3 were examined using real-time polymerase chain reaction (Real-time PCR), immunocytochemistry, western blot, and Sircol assay. Both DA3 and DA3-Doxy exhibited cytotoxicity at 10 μg/ml in nasal fibroblasts. Doxy partially inhibited α-smooth muscle actin, collagen types I and III, and fibronectin. However, DA3-Doxy significantly inhibited α-SMA, collagen types I and III, and fibronectin at 5 μg/ml. DA3-Doxy also modulated TGF-β1-induced changes in the expression of MMP 1, 2, and 9. Nonetheless, TGF-β1-induced expression of MMP3 was further increased by DA3-Doxy. The expression of TIMP 1 and 2 was partially reduced with 5 μg/ml DA3-Doxy. Although initially developed for the delivery of genetic materials or drugs, DA3 exhibits inhibitory effects on myofibroblast differentiation and ECM production. Therefore, it holds therapeutic potential for CRS, and a synergistic effect can be expected when loaded with CRS treatment drugs.

Cationic micelle delivery of a multi-epitope vaccine candidate derived from tumor-associated antigens, causing regression in established CT26 colorectal tumors in mice.

Among all the cancers, colorectal cancer (CRC) has the third mortality rank in both genders. Cancer vaccines have shown promising results in boosting patients' immune systems to fight cancer. Using the IEDB database, we predicted mouse MHC-I (H2-Ld) binding epitopes from four tumor-associated antigens (APC, KRAS, TP53, and PIK3CA) and designed a multi-epitope vaccine. We expressed the candidate vaccine and encapsulated it into the cationic micelle with polyethyleneimine conjugated to oleic acid as its building blocks. We studied tumor inhibition effect, cytokine production, and lymphocyte proliferation in the mouse CRC model after vaccination. Our finding illustrated significant tumor growth inhibition in mouse models treated with the candidate nanovaccine. Besides the significant release of IFN-γ and IL-4 by immunized mouse spleen T-lymphocytes, T-cell proliferation assay results confirmed effective immune response after the vaccination. These results demonstrate the potential therapeutic effects of nanovaccines and could be a possible approach to CRC immunotherapy.

Amphiphilic polylactic acid-b-poly(N-(3-aminopropyl) methacrylamide) copolymers: Self-assembly to polymeric micelles for gene delivery

In this study, for the first time diblock copolymers of PLA-b-PAPMA with three different sizes were synthesized in order to fabricate cationic micelles. In this copolymer, p(APMA) block with hydrophilic cationic nature could serve as a nucleic acid condensation platform as well as the shell of micellar structure in the self-assembly process. The p(APMA) block was electrostatically complexed with nucleic acid, and formed a neutral or mildly positive charge micellar surface, thus providing the nanoparticles safety and stability. On the other hand, polylactic acid as a hydrophobic polymer in diblock copolymer structure formed core of micelles which could encapsulate hydrophobic therapeutics. The synthesized copolymers, PLA74-b-PAPMA14, PLA121-b-PAPMA22, PLA121-b-PAPMA103 were evaluated in terms of self-assembly capability, size, polydispersity index, plasmid condensation, transfection efficacy and cytotoxicity against C26 cells. Obtained results demonstrated low CMC values for all copolymers. PLA121-b-PAPMA103 diblock copolymer condensed green fluorescent protein plasmid at C/P 1 and higher, while other diblock copolymers were able to condense plasmid above C/P 70. The self-assembly structures of cationic micelles before and after plasmid condensation showed spherical morphology in SEM analysis while DLS data illustrated appropriate size (161.7 ± 8) and PDI (0.276) for PLA121-b-PAPMA103 diblock copolymer. It could be concluded that the cationic micelles with approximately the molecular weight ratio of hydrophilic block to total polymer mass of 60 % and larger than 50 % provided higher stability, condensation ability and transfection efficiency which could be attributed to the better self-assembly process and better amine groups exposure on the micellar surface.

Self-assembled low molecular weight chitosan-based cationic micelle for improved water solubility, stability and sustained release of α-tocopherol.

New amphiphilic low molecular weight chitosan-graft-nicotinic acid bearing decyl groups (LCND) was synthesized by two-step reaction and spontaneously assembled into cationic micelle by ultra-sonication method to improve water solubility and photostability properties of α-tocopherol. The chemical structure of LCND was characterized and physical properties of cationic micelle were evaluated. Results displayed that cationic micelle exhibited strong self-assemble ability with nanoscale spherical morphology and showed best loading ability with loading content of 18.50% when the feeding ratio of LCND to α-tocopherol reached 10:3. Meanwhile, the greatly enhanced water solubility, photostability and sustained release behavior of α-tocopherol in cationic micelle were observed. The cumulative release of α-tocopherol in cationic micelle reached up 82.18% within 96h while free α-tocopherol was completely released within 10h. Additionally, release kinetics models were also fitted. The LCND cationic micelle could be promising nanocarrier for improving the physicochemical properties of α-tocopherol in food fields.

Interaction of anti-inflammatory drug nimesulide with ionic and non-ionic surfactant micelles: Insights from spectral and bioinformatics approach

The present work reports the interaction of anti-inflammatory drug nimesulide with cationic (CTAB, HDPC), anionic (SDS) and non-ionic (Triton X-100) surfactant micelles. The drug-micelles systems were studied by UV–Vis absorption spectroscopy to estimate the binding constant (Kb), partition coefficient (Kx) and the free energy of binding and partition (ΔGb, ΔGx). The values of Kb indicate a stronger interaction between nimesulide and cationic micelles due to cumulative electrostatic and hydrophobic forces. Also, the higher values of Kx obtained for HDPC and CTAB micelles point out a higher drug concentration in cationic micelles than in the surrounding aqueous medium, as against SDS and Triton X-100 micelles. The bioinformatic methods were used to evaluate the pharmacokinetic, pharmacogenomic and pharmacodynamic profiles of the nimesulide, CTAB, HDPC, SDS, and Triton X-100. Our results showed that all compounds exhibit good intestinal absorption, good BBB and CNS permeabilities, and low toxicity features. Also, the ecotoxicity of compounds was quantified. Various pharmacogenomic features of compounds were recorded. Supplementary, we conducted an extensive analysis based on various aspects of the structural and functional features of compounds, such as their electronic (dipole moment, frontiers orbital energies), steric, and hydrophobic features. Experimental and theoretical results show that CATB and HDPC cationic micelles may be better drug delivery agents for nimesulide.

Betaine-Based and Polyguanidine-Inserted Zwitterionic Micelle as a Promising Platform to Conquer the Intestinal Mucosal Barrier.

Developing nanocarriers for oral drug delivery is often hampered by the dilemma of balancing mucus permeation and epithelium absorption, since huge differences in surface properties are required for sequentially overcoming these two processes. Inspired by mucus-penetrating viruses that universally possess a dense charge distribution with equal opposite charges on their surfaces, we rationally designed and constructed a poly(carboxybetaine)-based and polyguanidine-inserted cationic micelle platform (hybrid micelle) for oral drug delivery. The optimized hybrid micelle exhibited a great capacity for sequentially overcoming the mucus and villi barriers. It was demonstrated that a longer zwitterionic chain was favorable for mucus diffusion for hybrid micelles but not conducive to cellular uptake. In addition, the significantly enhanced internalization absorption of hybrid micelles was attributed to the synergistic effect of polyguanidine and proton-assisted amine acid transporter 1 (PAT1). Moreover, the retrograde pathway was mainly involved in the intracellular transport of hybrid micelles and transcytosis delivery. Furthermore, the prominent intestinal mucosa absorption in situ and in vivo liver distribution of the oral hybrid micelle were both detected. The results of this study indicated that the hybrid micelles were capable of conquering the intestinal mucosal barrier, having a great potential for oral application of drugs with poor oral bioavailability.

Cationic Dextran Stearate (Dex-St-GTMAC): Synthesis and Evaluation as Polymeric Micelles for Indomethacin Corneal Penetration.

Background Indomethacin as a non-steroidal anti-inflammatory drug (NSAID) is commonly used to treat some ocular inflammatory disorders. Unfortunately, indomethacin is a drug that is poorly soluble in water; therefore, it has low efficacy. An attractive approach is the targeted delivery of indomethacin to the cornea using cationic dextran stearate as a polymeric micelle drug carrier. Methods A dextran stearate-glycidyl trimethylammonium chloride (Dex-St-GTMAC) copolymer was prepared through the reaction of GTMAC, stearoyl chloride, and dextran. Then, Dex-St-GTMAC was characterized by Fourier transform infrared (FT-IR) spectroscopy and 1H NMR spectroscopy. Dex-St-GTMAC forms micelles in the presence of indomethacin. The prepared polymeric micelles were characterized for size, ζ-potential, drug loading, particle morphology, critical micelle concentration, and encapsulation efficiency. To study the irritation potential of the indomethacin-loaded Dex-St-GTMAC, Het-Cam and Draize tests have been performed. Prepared cationic micelles were subjected to the in vitro drug release and ex vivotrans-corneal permeation test. Results The dialysis method was used for the preparation of indomethacin-loaded micelles (10, 20, and 30%). Measurement of the particle size showed a mean diameter of 122.1 and 150.9 nm for the drug-loaded micelles. Scanning electron microscopy (SEM) images showed that the morphology of the particles is spherical. 10% formulation was chosen as the best formulation due to more surface charge and reasonable drug loading. ζ-potential measurement for the 10% drug-containing micelles showed a value of +39.1 mV. Drug loading efficiency and the encapsulation efficiency for 10% drug-containing micelles were 6.36 and 63.61%, respectively. The results of the Het-Cam and Draize tests indicated that the indomethacin-loaded Dex-St-GTMAC formulation had no toxicity to eye tissues. Based on our results, the prepared micelles (indomethacin-loaded Dex-St-GTMAC) exhibited a sustained drug release pattern compared to the control group. Indomethacin penetration from the micelles to the excised bovine cornea was 1.75-fold greater than the control (indomethacin 0.1% in phosphate-buffered saline (PBS)). Conclusions Data from the ζ-potential, SEM, drug loading capacity, and in vitro drug release studies indicated that cationic dextran stearate polymeric micelles are an appropriate carrier for the efficient penetration of indomethacin into cornea tissues.

The Formation Analysis of Ca (II), Mg (II), Zn (II) and 5-Hydroxysalicylic Acid Binary Complexes in Cetyltrimethylammonium Bromide Cationic Micelles

The Formation Analysis of Ca (II), Mg (II), Zn (II) and 5-Hydroxysalicylic Acid Binary Complexes in Cetyltrimethylammonium Bromide Cationic Micelles