Zeta Potential Of Micelles Research Articles

Formulation and optimization of aceclofenac loaded hyaluronic-oleic acid based micellar gel for the management of osteoarthritis

Aceclofenac is a non-steroidal anti-inflammatory drug used to manage osteoarthritis. However, its limited solubility, short half-life, and gastrointestinal side effects on chronic use limit its delivery via the oral route. This study used hyaluronic acid tailored with oleic acid via esterification to formulate micelles for aceclofenac topical delivery. The prepared micelles were characterized for average particle size, size distribution, surface charge, drug loading, entrapment efficiency, and surface morphology. The drug loading, entrapment efficiency, mean particle size, and zeta potential of micelles were 8.21 ± 0.3%, 81.25 ± 2.98%, 245.93 ± 7.68 nm, and −17.6 ± 1.95 mV, respectively. The prepared micelles were found to be spherical. The micelles were further loaded in chitosan gel and evaluated for drug release, skin permeation, and deposition. The hydrogel showed shear thinning behavior, sustained drug release, enhanced skin permeation, and deposition of aceclofenac. Further, the pharmacodynamic study revealed a significant reduction in pain and inflammatory response with an improved radiological and histopathological condition in the animal models. These results show the potential of hyaluronic acid oleic acid conjugate micellar gel as a promising carrier to deliver the poorly soluble small molecules like aceclofenac topically to manage the inflammatory condition.

In vitro Characterization of Polyethyleneimine-Oleic Acid Cationic Micelle as a Novel Protein Carrier.

Nanotechnology has introduced valuable carriers for vaccine delivery. The success of vaccination depends on many factors, such as the intact and safe presentation of vaccine candidates to immune cells. We have conjugated branched PEI-2k and oleic acid (OL) as the building block of the cationic micelle. We aimed to introduce a novel carrier for vaccine candidates. We conjugated polyethyleneimine and OL (POA) to synthesize the building blocks of cationic micelles. The critical micelle concentration (CMC), size and zeta potential of micelles, and their stability in 60 days were determined. Loading, encapsulation efficiency, and in vitro release study were assessed using bovine serum albumin (BSA) as a protein model. Furthermore, the cytotoxicity and hemocompatibility of developed nanosized micelles were evaluated to ascertain the biocompatibility of fabricated micelles. Cell uptake of cationic micelles in the macrophage cell line was also followed up. The conjugation of two polymer parts was confirmed by Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance techniques. The CMC of the developed micelles was around 5.62 × 10-8 mg/ ml, whereas the loading and encapsulation efficiencies were 16.5% and 70%, respectively. The size and zeta potential of the cationic micelles were 96.53 ± 18.53 nm and 68.3 mV, respectively. The release of BSA from POA micelles after 8 and 72 hours was 8.5% and 82%, respectively. Finally, fluorescence microscopy showed that the prepared micelles were successfully and effectively taken up by RAW264.7 cells. These results may provide a cutting-edge vaccine delivery solution and open up a new avenue for future vaccine research.

Intelligent self-assembly prodrug micelles loading doxorubicin in response to tumor microenvironment for targeted tumors therapy

Compared with physical drug-loaded nanocarriers, polymeric prodrug micelles have many advantages such as high drug loading and enhanced stability in blood, so they have great potential in cancer therapy. However, these micelles have a big disadvantage, which cannot achieve long-term circulation in vivo and high absorption of tumor cells simultaneously, resulting in low administration efficiency and poor therapeutic effect on cancer. To solve problems of traditional polymeric prodrug micelles, novel polymeric micelles with tumor microenvironment response were designed in this work. The prodrug formed by covalently linking D-α-tocopherol polyethylene glycol succinate (TPGS 3350 ), peptide (Pep), and doxorubicin (DOX) (TPGS 3350 -Pep-DOX) was self-assembled into micelles by encapsulating DOX physically. When the micelles entered the tumor tissue, the long-chain polyethylene glycol (PEG) was sensitively cut by the matrix metalloproteinase 2/9 (MMP2/9) enzyme, exposing the targeting molecule folate, then it entered the cell through the endocytic pathway mediated by the folate receptor. The drug loading content, encapsulation efficiency, critical micelle concentration, and invitro release of the micelles invented in this study were measured to characterize their properties. The particle size and zeta potential of micelles were characterized by dynamic light scattering. Images were scanned by transmission electron microscopes. In vitro cytotoxicity, cellular uptake, and in vivo antitumor effect evaluation experiments were measured to show that smart micelles have made much progress in material chemistry and drug delivery, making it possible to apply a stimulus–response carrier drug delivery system in clinical application.

Doxorubicin-loaded folate-mediated pH-responsive micelle based on Bletilla striata polysaccharide: Release mechanism, cellular uptake mechanism, distribution, pharmacokinetics, and antitumor effects

This study evaluated the potential of folate (FA)-mediated and stearic acid (SA) modified Bletilla striata polysaccharide (FA-BSP-SA) copolymer as the vehicle for targeted delivery of anticancer drugs to tumor tissues and enhanced antitumor efficacy. The critical aggregation concentration, morphology, particle size, and zeta potential of micelles were increased with the reduction of pH values. The complex between doxorubicin (Dox) hydrochloride and sodium cholate via electrostatic interaction was fabricated and then directly encapsulated into FA-BSP-SA micelles. Dox in micelles existed in the status of amorphism. The Dox/FA-BSP-SA micelles demonstrated pH-responsive release behavior under the combination of diffusion and erosion mechanism. They could clearly strengthen the cellular uptake of Dox and inhibit the proliferation and the migration of tumor cells compared with the Dox/BSP-SA micelles and the free Dox. The Dox/FA-BSP-SA micelles were further delivered to lysosomes, mainly due to clathrin-mediated endocytosis. The FA-BSP-SA micelles distinctly improved the absolute bioavailability of Dox compared with the free Dox and the Dox/BSP-SA micelles (p < 0.01) and prolong the mean residence time. The Dox/FA-BSP-SA micelles significantly increased the drug enrichment in the tumor sites and enhanced the antitumor effects in vivo. Taken together, the FA-BSP-SA micelle could be exploited as a potential platform for targeting anticancer drug delivery.

Preparation and optimization of biodegradable self-assembled PCL-PEG-PCL nano-sized micelles for drug delivery systems

Biodegradable polymeric micelles have potential therapeutic applications; nevertheless, preparing micelles of a specific diameter and uniform size distribution is a challenge. Micelles were formed from the copolymer of poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) and the effect of PCEC molecular weight, PCL/PEG ratio, solvent-water miscibility, solvent concentration on particle size, polydispersity index and zeta potential of micelles were also investigated. The average particle sizes of the PCEC micelles ranged between 225–959 and 232–1211 nm for micelles prepared with acetone and dimethylformamide, respectively. The encapsulation efficiency is 78.98%. These results indicate that PCEC micelles can be used as drug carriers in controlled delivery systems.

In vivo study of mPEG–PCL as a nanocarriers for anti-inflammatory drug delivery of simvastatin

Purpose: In this study, methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG–PCL) di-block copolymers were synthesized. The purpose of this work is to investigate the in vivo anti-inflammatory effects of simvastatin-loaded micelles.Methods: The structure of synthesized copolymers was characterized by using HNMR, FTIR, and GPC techniques. Simvastatin was encapsulated in micelles through a single-step nano-precipitation method, leading to the formation of simvastatin-loaded mPEG–PCL (simvastatin-mPEG–PCL) micelles. In this study, the anti-inflammatory effects of simvastatin/mPEG–PCL micelles versus indomethacin were investigated in acute inflammation-induced rats. The paw edema thickness was measured 1, 2, 3, and 4 h after injection of formulation. The inhibition of edema in various groups were calculated and reported by percentages.Results: The results showed that the zeta potential of micelles was about −14.9 ± 0.47 mV and the average size was in range of 66.10 ± 0.34 nm. Simvastatin was encapsulated in mPEG–PCL micelles with a loading capacity of 9.63 ± 0.87% and an encapsulation efficiency of 64.20 ± 0.79%. Simvastatin and simvastatin-mPEG–PCL micelles showed significant anti-inflammatory activity in the present study.Conclusions: This study revealed that simvastatin and simvastatin/mPEG–PCL micelles both have anti-inflammatory effects and suggested that statins have potential anti-inflammatory activity along with their lipid lowering properties.

Enhanced Therapeutic Effect of RGD-Modified Polymeric Micelles Loaded With Low-Dose Methotrexate and Nimesulide on Rheumatoid Arthritis.

Angiogenesis plays an essential role in the progression of rheumatoid arthritis (RA). RGD peptide shows high affinity and selectivity for integrin αvβ3, which is one of the most extensively examined target of angiogenesis. Nimesulide could improve the anti-rheumatic profile of methotrexate. But the clinical application was limited due to water-insolubility of both methotrexate and nimesulide and lacking targeting ability. Therefore, this study aimed to design a targeted drug delivery system of micelles mediated by RGD plus the passive targeting of micelles to solve the application problems of methotrexate and nimesulide (M/N), and thus enhance their combined therapeutic effect on RA.Methods: RGD was conjugated with NHS-PEG-PLA to form RGD-PEG-PLA for the preparation of RGD-modified drug-loaded micelles (R-M/N-PMs). The size and zeta potential of micelles were measured by dynamic light scattering. Morphology was detected by transmission electron microscopy. The inhibition effect of R-M/N-PMs on angiogenesis was assessed by the chick chorioallantoic membrane assay. The real-time fluorescence imaging analysis was conducted to examine the in vivo distribution of the fluorescence-labeled R-M/N-PMs. Rats arthritis model induced by Freund's adjuvant was used to evaluate the in vivo anti-inflammatory efficacy of R-M/N-PMs.Results: The in vitro study indicated successful development of R-M/N-PMs. R-M/N-PMs could markedly suppress the angiogenesis of chick embryos. The fluorescence-labeled R-M/N-PMs mainly accumulated in arthritic joints. RGD enhanced the targeting ability of micelles and thus promoted retention of micelles in arthritic joints. Moreover, R-M/N-PMs significantly alleviated the joint swelling while reducing bone erosion and serum levels of inflammatory cytokines. It helped to recover the bone microstructure of arthritic rats.Conclusion: Our results confirmed that the targeted delivery of the combination of a low dose of methotrexate and nimesulide mediated by RGD-modified polymeric micelles could enhance the therapeutic effect on rheumatoid arthritis. These findings provide a promising potential for the clinical therapy of rheumatoid arthritis.

In vitro and in vivo delivery of gliclazide loaded mPEG-PCL micelles and its kinetic release and solubility study

In this study, drug delivery system of gliclazide, a poorly soluble drug, was developed and evaluated in vitro and in vivo. We synthesized five series of mPEG-PCL di block copolymers. The structure of the copolymers was characterized by 1H-NMR, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) techniques. In this study, gliclazide was encapsulated within micelles through a single-step nano-precipitation method, leading to formation of gliclazide/mPEG-PCL micelles. The resulting micelles were characterized further by various techniques such as DLS and AFM. The serum glucose lowering effect of gliclazide micelles was studied in streptozotocin-diabetic rats and were compared with the gliclazide treated rats. The results showed that the zeta potential of micelles was about −14.9 mV and the average size was 83.12 nm. Gliclazide was encapsulated into mPEG-PCL micelles with loading capacity of 21.05 ± 0.14% and entrapment efficiency of 94.11 ± 0.12%. In vivo testing of the gliclazide micelles in diabetic rats demonstrated a significant antidiabetic effect of gliclazide micelles after the 7 day that lasted for 21 days when compared with gliclazide powder. The results suggest that gliclazide micelles are a valuable system for the sustained delivery of gliclazide.

Polymer Micelles Laden Hydrogel Contact Lenses for Ophthalmic Drug Delivery.

Hydrogel contact lens is an attractive drug carrier for the delivery of ophthalmic drugs. But limited drug loading capacity and burst release restricted its application in this field. Polymer micelle laden hydrogel contact lenses were designed for ophthalmic drug delivery in the work. β-CD/PAA/PEG ternary system was chosen to form polymer micelle. The micelle size could be adjusted by β-CD content and PAA/PEG concentration. The zeta potential of micelle was irrelevant to β-CD content, but influenced by PAA/PEG concentration. The absorbed drug concentration in micelle solution depended on both β-CD content and PAA/PEG concentration. Polymer micelle laden hydrogels were obtained by radical polymerization in situ. The transparency of polymer micelle laden hydrogel declined with PAA/PEG concentration increasing. The equilibrium water content and water loss showed that polymer micelle laden hydrogel with higher PAA/PEG concentration was in a higher swollen state. The dynamic viscoelastic properties howed that all polymer micelle laden hydrogels had some characteristics of crosslinked elastomers. The surface structure of freeze dried composite hydrogels was different from freeze dried pure hydrogel. The drug loading and releasing behaviors were detected to evaluate the drug loading and releasing capacity of hydrogels using orfloxacin and puerarin as model drugs. The results indicated the polymer micelle in hydrogel could hold or help to hold some ophthalmic drugs, and slow down orfloxacin release speed or keep puerarin stably stay for a time in hydrogels. In the end, it was found that the transparency of composite hydrogel became better after the hydrogel had been immersed in PBS for several weeks.

Zwitterionic polymeric micelles that undergo a pH-triggered positive charge for enhanced cellular uptake

To achieve a good stealth property and to enhance the uptake by tumor cells, polymeric micelles containing a slightly negatively charged and zwitterionic corona at pH 7.4 (i.e., blood pH) and a positively charged surface at a slightly acidic pH (i.e., tumor extracellular pH) were prepared. The amphiphilic diblock copolymer which was used to prepare the polymeric micelles contains a hydrophilic block comprised of nonionic hydrophilic groups, negatively charged groups (carboxyl groups) and pH-triggered positive charge-generation groups (morpholino groups). The zeta potential of the micelles was found to increase as the pH decreased over the pH range covering the blood and tumor tissue pH ranges, and the corona of the micelles should contain zwitterionic groups. This could be due to that, in the pH range studied, more morpholino groups become protonated as the pH decreased, whereas the carboxyl groups were almost completely deprotonated to form carboxylate anions. Furthermore, by adjusting the molar ratio of morpholino to carboxyl groups, the zeta potential of the polymeric micelles was controlled to achieve a slightly negative value at pH 7.4. Thus, the combination of a slightly negatively charged surface and a zwitterionic corona suggests that these micelles would possess good stealth property. When the pH decreased from 7.4 to 6.8 or 6.5, the zeta potential value of the micelles became positive due to increased protonation of the morpholino groups. Correspondingly, the cellular uptake of the micelles by HeLa cells was enhanced.

Effect of surface charge of polymeric micelles on in vitro cellular uptake

This work focuses on the interaction between polymeric micelles with different charged surfaces and cancer cells in order to study the influence of surface charge on the in vitro cellular uptake efficiency. The amphiphilic diblock copolymers poly(ɛ-caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) with different functional groups at the end of hydrophilic block were synthesized. The functional groups endue the micelles with different charges on the surfaces. The cellular uptake of micelles to T-24 cells (human bladder tumor cells), HepG2 cells (human liver hepatocellular carcinoma cell line) and Hela cells (human epithelial cervical cancer cells) was studied by means of flow cytometer and confocal laser scanning microscopy. The results indicate that the surface charges showed great influence on zeta potential of micelles at different pH values. The in vitro cellular uptake efficiency of micelles with different charged surfaces demonstrated different cellular uptake patterns to three kinds of cancer cells.

Counter‐ion Effect on Micellization of Ionic Surfactants: A Comprehensive Understanding with Two Representatives, Sodium Dodecyl Sulfate (SDS) and Dodecyltrimethylammonium Bromide (DTAB)

AbstractVarious micelle parameters viz., critical micelle concentration (CMC), counter‐ion binding (β), aggregation number (N), hydrodynamic radius (Rh), micelle zeta potential (ζ) and energetic parameters, free energy of micellization (), enthalpy of micellization () and entropy of micelle formation () were determined for sodium dodecylsulfate, and dodecyltrimethylammonium bromide in the presence of NaCl for the former and NaBr for the latter. Conductometry and calorimetry methods were used for the measurements of CMC and energetic parameters. The fluorimetric (static quenching) method was employed to determine N and dynamic light scattering to estimate Rh and ζ. The conductometrically determined β was verified from the CMC values by calorimetry using the Corrin–Harkins equation. The results found for the two surfactants of identical tails but different head groups have been presented and discussed. A detailed report on the salt effect using salts containing counter‐ions the same as those in the surfactant is found only limitedly in the literature.

Bulk properties of nonionic surfactant and chitosan mixtures

Bulk properties in mixtures of the nonionic surfactant Lutrol ® F127 and cationic polyelectrolyte chitosan in water and acetate buffer (pH 6.0 and 6.5 and ionic strength 0.1 and 0.5, respectively) were studied by fluorescence spectroscopy, dynamic light scattering and zeta potential measurements. It was observed that the addition of chitosan to F127 systems in water had little effect on critical micelle concentration (cmc) values. On the contrary, the addition of chitosan to F127 systems in acetate buffer shifted cmc to higher values. Independently of pH and ionic strength, the cmc increase was more pronounced as the chitosan concentration in the system increased. The antagonistic mixing behaviour of the present nonionic surfactant and polyelectrolyte was observed at pH 6.5 and an ionic strength of 0.5 at 34 °C. The micelles in mixed F127/chitosan systems had an average hydrodynamic diameter of 25 nm and were larger than F127 micelles themselves (22.5 nm). The zeta potential of micelles in F127 water systems and in both acetate buffer systems was almost neutral, due to the nonionic nature of F127. In water and both acetate buffer mixed F127/chitosan systems, the zeta potential of micelles was positive and increased with increasing chitosan concentration, due to the electropositive charge of chitosan. The effect was more pronounced in water systems. Results are discussed in terms of electrostatic, hydrophobic and interpolymer interactions.