Delivery System For Hydrophobic Drugs Research Articles

Nanosponges-Road Less Explored Changing Drug Delivery Approach: An Explicative Review.

Nanotechnology exhibits a wide range of applications in the domain of disease therapy, diagnosis, biological detection, and environmental safeguards. The cross-linked polymeric nanosponges (NSs) are a nanoscale drug carrier system with a 3D porous structure and high entrapment efficacy. NSs up to the fourth generation are currently accessible and can serve as a delivery system for both hydrophilic and hydrophobic drugs. The delivery system exhibits superiority over alternative methods due to its ability to achieve controlled and targeted drug delivery. The colloidal structure of NSs facilitates the encapsulation of a wide range of agents such as proteins and peptides, enzymes, antineoplastic drugs, volatile oil, vaccines, DNA, etc. NSs efficiently overcome the challenges associated with drug toxicity and poor aqueous solubility. NS formulations have been explored for various applications like gaseous encapsulation, enzyme immobilization, antifungal therapy, poison absorbent, water purification, etc. This review provides a comprehensive analysis regarding methods of synthesis, distinct polymeric NSs, mechanism of drug release, factors affecting NS development, applications, and patents filed in the field of NSs. Herein, the recently developed NS formulations, their potential in cancer therapy, and current progressions of NS for SARS-CoV-2 management are also deliberated with special attention, focusing on the significant challenges and future directions.

Nanosponges-Road Less Explored Changing Drug Delivery Approach: An Explicative Review.

Nanotechnology exhibits a wide range of applications in the domain of disease therapy, diagnosis, biological detection, and environmental safeguards. The cross-linked polymeric nanosponges (NSs) are a nanoscale drug carrier system with a 3D porous structure and high entrapment efficacy. NSs up to the fourth generation are currently accessible and can serve as a delivery system for both hydrophilic and hydrophobic drugs. The delivery system exhibits superiority over alternative methods due to its ability to achieve controlled and targeted drug delivery. The colloidal structure of NSs facilitates the encapsulation of a wide range of agents such as proteins and peptides, enzymes, antineoplastic drugs, volatile oil, vaccines, DNA, etc. NSs efficiently overcome the challenges associated with drug toxicity and poor aqueous solubility. NS formulations have been explored for various applications like gaseous encapsulation, enzyme immobilization, antifungal therapy, poison absorbent, water purification, etc. This review provides a comprehensive analysis regarding methods of synthesis, distinct polymeric NSs, mechanism of drug release, factors affecting NS development, applications, and patents filed in the field of NSs. Herein, the recently developed NS formulations, their potential in cancer therapy, and current progressions of NS for SARS-CoV-2 management are also deliberated with special attention, focusing on the significant challenges and future directions.

Synthesis and characterization of the redox-responsive amphiphilic fluorescent alginate derivatives as the multi-functional hydrophobic anticancer drug delivery system with visualization and sustained release

To develop the multi-functional hydrophobic anticancer drug carriers with visualization and sustained release, a novel amphiphilic alginate derivative (LSA-SS-DEAC) containing chromophobe groups was designed and synthesized by grafting hydrophobic fluorescent molecule, 7-(diethylamino-coumarin-3-carboxylic acid (DEAC-COOH) onto hydrophilic low molecular alginate backbone through cystamine by water-soluble carbodiimide chemical method. The molecular structure and self-assembly properties of the synthesized LSA-SS-DEAC were characterized. Furthermore, the encapsulation of anti-cancer drugs, doxorubicin hydrochloride (DOX) in LSA-SS-DEAC self-assembled micelles was realized by ultrasonic dialysis method. Subsequently, the in vitro drug release behavior and in vitro cytotoxicity of LSA-SS-DEAC micelles in simulated tumor microenvironment were also studied. The resultant LSA-SS-DEAC with the critical micelle concentration (CMC) of 0.26 mg/mL exhibited the ability to spontaneously form spherical micelles with the particle size of 250.2 ± 4.3 nm (PDI = 0.23) and zeta potential of −49.1 ± 0.4 mV, which presented good stability in pH 7.4 PBS and excellent fluorescence properties and redox responsiveness. The drug-loaded LSA-SS-DEAC micelles had the optimal EE value of about 42.2% when the DOX/LSA-SS-DEAC mass ratio was 3:10. Meanwhile, The drug-loaded LSA-SS-DEAC micelles exhibited sustained release in GSH-free environment, and the cumulative drug release rates were 40.3% and 46.6% in pH 7.4 and 5.0 PBS for 48 h, respectively. However, in the simulated tumor cell microenvironment (pH 5.0 PBS + 10 mM GSH), the disulfide bond between the core-shell was broken under the GSH trigger, and the LSA-SS-DEAC micelles collapsed, resulting in a cumulative drug release rate of about 64% at 12 h. In vitro cytotoxicity results showed that LSA-SS-DEAC had low cytotoxicity, and revealed obvious inhibitory effect on HeLa cells after DOX loading. Fluorescence imaging results indicated that LSA-SS-DEAC micelles could emit green light after ingested by cells, and their fluorescence properties were not affected after encapsulation of DOX. Accordingly, LSA-SS-DEAC micelles had the potential for drug localization tracking and rapid drug release at focal sites, which could be expected to be an ideal drug carriers for hydrophobic anticancer drug delivery.

Bilosomes: An Overview of Advancements in Preparation, Characterization, and Applications

Bilosomes, also known as bile vesicles, are bilayer vesicles that are formed by the hydration of bile salts. They have gained significant attention in recent years due to their potential use in various applications, including drug delivery and nutraceuticals. In this review, we discuss the various techniques used for the preparation of Bilosomes, including the film hydration, reverse phase evaporation, and ether injection methods. We also discuss the characterization techniques used to study the properties of Bilosomes, such as transmission electron microscopy (TEM), dynamic light scattering (DLS), and small angle X-ray scattering (SAXS). Additionally, we discuss the potential applications of Bilosomes, including their use as drug delivery systems for hydrophobic drugs, as well as their use in the food and nutraceutical industries. Finally, we discuss the current state of the Bilosomes market, including the currently available commercial products. Overall, this review provides a comprehensive overview of the recent advancements in Bilosomes research and highlights the potential of Bilosomes in various fields.

Alginate hydrogel incorporating cellulose nanofiber from solid waste agar industry for hydrophobic antibiotic delivery: Synthesis and characterization

Undoubtedly, there is an increasing inclination towards the development of hydrogels derived from natural sources for the purpose of delivering hydrophobic antibiotics. In this study, alginate hydrogels containing cellulose nanofibrils (CNF) were synthesized from solid waste agar industry (SWAI) via Hydrated deep eutectic solvent (DES) hydrolysis and mechanical treatment, intending to encapsulate chloramphenicol and examine the properties of the alginate-CNF (ALG-CNF) hydrogel at various CNF concentrations. The CNF displays a fibrous morphology, surface charge of − 39.3 ± 0.3 mV, 62.95% crystallinity, and type-I cellulose. The incorporation of CNF notably affected the characteristics of the ALG-CNF hydrogel. Chloramphenicol was effectively encapsulated within the ALG-CNF hydrogel matrix. Chloramphenicol release showed a biphasic profile, with controlled release occurring within 48 h. The drug release kinetics adhered to the Korsmeyer-Peppas model, reflecting pseudo-Fickian diffusion (n < 0.45), with a high determination coefficient (R² ≈ 0.95). Antibacterial susceptibility tests demonstrated that ALG-CNF hydrogels inhibited the growth of E. coli, S. aureus, and P. aeruginosa. The ALG-CNF hydrogel demonstrated favorable physical properties, drug release, and antibacterial properties, making it a prospective candidate for future studies on wound dressings and hydrophobic drug delivery systems.

GELLAN GUM- AND PECTIN-MAGNETIC GRAPHENE OXIDE NANOCARRIERS LOADED WITH CINNAMALDEHYDE FOR MOSQUITO LARVAE CONTROL

Magnetic nanoparticles have evolved over the last few decades as nanocarriers in drug delivery systems for hydrophobic drugs. Here, novel gellan gum magnetic graphene oxide (GG-GO-Fe3O4) and pectin magnetic graphene oxide (PEC-GO-Fe3O4) nanocomposites were prepared to carry cinnamaldehyde to control Aedes aegypti larvae. Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM) and scanning transmission electron microscopy (STEM) were employed to investigate the physicochemical characteristics of the nanocomposites. Entrapment efficiencies and loading capacities of nanocomposites on cinnamaldehyde were examined using ultraviolet-visible analysis. The successful cinnamaldehyde loading was confirmed by C-C and C-O stretches in the FTIR spectra. Results of in vitro release study showed the capabilities of GG-GO-Fe3O4 as a drug carrier system, extending the cinnamaldehyde release period for 36 h, and the release profiles for both nanocomposites fit the Korsmeyer-Peppas kinetic model with correlation coefficient (R2) values of over 0.9809. The cinnamaldehyde-loaded GG-GO-Fe3O4 nanocomposites induced 68% mortality after 72 h of exposure, with LC50 values ranging from 2.0488 and 15.9121 mg/L. The conjugation of GO-Fe3O4 with biopolymers improved the water solubility of cinnamaldehyde by 36.41 to 62.83 times vs. free cinnamaldehyde in water (1.42 mg/mL). Overall, these results are beneficial for researchers dealing with mosquito control and prevention.

Amphiphilic conjugates for solubilization of paclitaxel as efficient drug carriers based on hyaluronic acid and cyclodextrins

Despite paclitaxel (PTX) as the first-line anti-tumor drugs, the unsatisfactory low-solubility in water remained a barrier to clinical application. Thus, the present study aimed at enhancing the solubility of PTX. Accordingly, we designed the amphiphilic conjugates (HP) as the delivery system and prepared self-assembly nanoparticles by the conjugates. Hemolysis assays showed the good biocompatibility of the conjugates. Meanwhile, binding affinity between the conjugates and PTX was explored based on the critical aggregation concentration (cac). The biggest solubilization for the nanoparticles was 193.56-fold, which exhibited as the solubility of 48.39 μg/mL. Cellular uptake assays revealed the valid internalization of nanoparticles and the targetability. In addition, the nanoparticles arrested the mitosis and further apoptosis. Cytotoxicity and three-dimensional multicellular spheroid (3DMCS) assays proved the strong growth inhibition capacity and the superior penetration ability for the nanoparticles. These results suggested that the HP conjugate we synthesized could provide potential insights into the delivery system for hydrophobic drugs on the aspects of anti-tumor.

Layered Double Hydroxides as an Intercalation System for Hydrophobic Molecules.

Layered double hydroxides (LDHs) have been extensively studied as drug delivery systems due to their favorable characteristics, including biocompatibility, high loading efficiency, and pH-responsive release. However, the current research predominantly focuses on LDHs as carriers for various anionic drugs, while there are only limited reports on LDHs as carriers for hydrophobic drugs. In this study, we successfully achieved the loading of a hydrophobic drug mimic, Nile red (NR), into LDHs using sodium dodecyl sulfate (SDS) as an intermediate storage medium. Furthermore, we optimized the experimental methods and varied the SDS/NR molar ratio to optimize this intercalation system. With an increase in the SDS/NR molar ratio from 2/1 to 32/1, the loading efficiency of LDH-SDS-NR for NR initially increased from 1.32% for LDH-SDS-NR_2/1 to 4.46% for LDH-SDS-NR_8/1. Then, the loading efficiency slightly decreased to 3.64% for LDH-SDS-NR_16.8/1, but then increased again to 6.31% for LDH-SDS-NR_32/1. We believe that the established method and the obtained results in this study broaden the application scope of LDHs as delivery systems for hydrophobic drugs and contribute to the further expansion of the application scope of LDHs.

Formulation and evaluation of paclitaxel-loaded boronated chitosan/alginate nanoparticles as a mucoadhesive system for localized cervical cancer drug delivery.

Cervical cancer remains a significant global health challenge, and there is a need for innovative drug delivery systems to improve the efficacy of anticancer drugs. In this study, we developed and evaluated boronated chitosan/alginate nanoparticles (BCHIALG NPs) as a localized mucoadhesive drug delivery system for cervical cancer. Boronated chitosan (BCHI) was synthesized by incorporating 4-carboxyphenylboronic acid onto chitosan (CHI), and boronated chitosan/alginate nanoparticles (BCHIALG NPs) with varying polymer ratios were prepared using an ionic gelation method. The physical properties, drug loading capacity/encapsulation efficiency, mucoadhesive properties, and in vitro drug release profile of the nanoparticles were evaluated. The BCHIALG NPs exhibited a size of less than 390 nm and demonstrated high drug encapsulation efficiency (98.1 - 99.8%) and loading capacity (326.9 - 332.7 μg/mg). Remarkably, the BCHIALG NPs containing 0.03% boronated chitosan and 0.07% alginate showed superior mucoadhesive capability compared to CHIALG NPs, providing sustained drug release and they showed the most promising results as a transmucosal drug delivery system for hydrophobic drugs like paclitaxel (PTX). To the best of our knowledge, this is the first report investigating BCHIALG NPs for cervical drug delivery. The new mucoadhesive paclitaxel formulation could offer an innovative strategy for improving cervical cancer treatment.

Recent progress in thermosensitive hydrogels and their applications in drug delivery area

AbstractThe scientific community has widely recognized thermosensitive hydrogels as highly biocompatible material with immense potential in drug delivery systems. When the temperature of these hydrogels approaches that of human body, a phase change occurs, enhancing their usefulness in a range of medical scenarios. This review article highlighted the background of thermosensitive hydrogels, their properties, and their applications in transdermal, oral, ophthalmic, intravaginal, nasal, rectal, cancer therapy, and cell‐loaded drug delivery systems. The literature suggests numerous advantages of these hydrogels over conventional drug delivery systems and find applications in various fields, such as therapeutic systems, filling processes, and sustained drug delivery systems. One of their key benefits is the ability to eliminate invasive procedures like surgery, providing a noninvasive alternative for drug administration. Moreover, they streamline the formulation process for both hydrophilic and hydrophobic drug delivery systems, simplifying the development of effective treatments. The thermosensitive hydrogels have been found to be green materials with negligible side effects and desirable drug delivery properties. The thermosensitive hydrogel's sustained‐release characteristics, immunogenicity, and biodegradability have also gained increased interest. Some of the disadvantages of thermosensitive hydrogels include delayed temperature response, weak mechanical characteristics, and poor biocompatibility, which limits their potential use in drug delivery applications.

Preparation of pH-sensitive lignin nanoparticles and its application in hydrophobic drug delivery

The majority of current oral drugs are hydrophobic, and have the toxic side effects to the gastrointestinal tract, which limit their therapeutic efficacy. In order to improve the performance of drug formulations, the development of new functional materials is crucial for the technological breakthroughs in the pharmaceutical industry. The antimicrobial and antioxidant properties of lignin nanoparticles (LNPs) give them great potential for application in this field. LNPs consist of a hydrophilic shell and hydrophobic core, which is particularly suitable for the capsulation of hydrophobic drugs, and then it would increase the stability and solubility of drugs and reduced the irritation to the stomach. In this study, alkali lignin (AL) was fractionated by 80% methanol to obtain targeted MAL with low molecular weight, high phenolic hydroxyl content and good homogeneity. The LNPs was prepared by quaternization modification of MAL and self-assembling in an ethanol/water mixture. Their application in the hydrophobic oral drug delivery system was evaluated and Ibuprofen (IBU) was used as a drug pattern. The effect of solvent exchange time (24 h, 36 h, 48 h and 60 h) on the formation process of IBU-loaded LNPs (IBU-LNPs) was investigated. The in vitro release experiments were conducted and it revealed that IBU release occurred priority in the intestine rather than the stomach, which were meeting the release requirements of ideal oral carrier. In addition, IBU-LNPs showed non-cytotoxic against the L929 cells and improved the bioavailability of IBU drugs. Therefore, this work proposes a preparation method of the smart lignin nanoparticle by screening characteristic lignin with higher reactivity and by modulating the solvent exchange time during the preparation process. Overall, LNPs showed the great potential of application in pharmaceuticals industry and was demonstrated a promising and green product.

Injectable Thermosensitive Nanocomposites Based on Poly(N-vinylcaprolactam) and Silica Particles for Localized Release of Hydrophilic and Hydrophobic Drugs.

The systemic delivery of drugs employed by conventional methods has shown to be less effective than a localized delivery system. Many drugs have the effectiveness reduced by fast clearance, increasing the amount required for an efficient treatment. One way to overcome this drawback is through the use of thermoresponsive polymers that undergo a sol-gel transition at physiological temperature, allowing their injection directly in the desired site. In this work, thermosensitive nanocomposites based on poly(N-vinylcaprolactam) and silica particles with 80 and 330 nm were synthesized to be employed as delivery systems for hydrophobic (naringin) and hydrophilic (doxorubicin hydrochloride) drugs. The insertion of SiO2 increased the rheological properties of the nanocomposite at 37 °C, which helps to prevent its diffusion away from the site of injection. The synthesized materials were also able to control the drug release for a period of 7 days under physiological conditions. Due to its higher hydrophobicity and better interaction with the PNVCL matrix, naringin presented a more controlled release. The Korsmeyer-Peppas model indicated different release mechanisms for each drug. At last, a preliminary in vitro study of DOX-loaded nanocomposites cultured with L929 and MB49 cells showed negligible toxic effects on healthy cells and better efficient inhibition of carcinoma cells.

Amphiphilic Polypeptides Obtained by the Post-Polymerization Modification of Poly(Glutamic Acid) and Their Evaluation as Delivery Systems for Hydrophobic Drugs.

Synthetic poly(amino acids) are a unique class of macromolecules imitating natural polypeptides and are widely considered as carriers for drug and gene delivery. In this work, we synthesized, characterized and studied the properties of amphiphilic copolymers obtained by the post-polymerization modification of poly(α,L-glutamic acid) with various hydrophobic and basic L-amino acids and D-glucosamine. The resulting glycopolypeptides were capable of forming nanoparticles that exhibited reduced macrophage uptake and were non-toxic to human lung epithelial cells (BEAS-2B). Moreover, the developed nanoparticles were suitable for loading hydrophobic cargo. In particular, paclitaxel nanoformulations had a size of 170-330 nm and demonstrated a high cytostatic efficacy against human lung adenocarcinoma (A549). In general, the obtained nanoparticles were comparable in terms of their characteristics and properties to those based on amphiphilic (glyco)polypeptides obtained by copolymerization methods.

Biointerfacial giant capsules with high paclitaxel loading and magnetic targeting for breast tumor therapy

High drug loading, targeted delivery, prolonged drug release, and low systemic toxicity are effective weapons for hydrophobic drug delivery systems to solve serious concerns in poor water-solubility and toxicity of paclitaxel (PTX). Herein, we reported that biointerfacial giant multilayer microcapsules (BGMs) with the feature of high-density drug loading and high-efficiency magnetic delivery were fabricated templated by PTX-liposome-microbubble complex using the layer-by-layer self-assembly (LbL) technique. The drug loading capacity of BGMs was improved by optimizing the structure of microbubbles and capsules to increase the PTX-contained layers, and the resultant BGMs exhibited high drug loading content (50.56 ± 0.09 %) and sustained drug release properties. The BGMs with an average diameter of 74.1 ± 12.1 µm and an average thickness of 275.5 ± 48.4 nm contained abundant magnetic nanoparticles (MNPs) in their cavity, which endowed these capsules with outstanding magnetic properties and fast magnetophoretic velocity in the blood (∼0.3 mm/s, ▽B = 1 T/mm). Moreover, both in vitro and in vivo studies demonstrated that the biocompatible PTX-loaded magnetic BGMs (Capsule@PLMPPL) caused notable death (71.3 ± 2.9 %) of 4 T1 breast cancer cells through PTX diffusion, capsules degradation, and subsequent endocytosis by cancer cells, and ultimately effectively inhibited tumor growth. In general, the developed BGM with good deformability and degradation was the first reported giant polyelectrolyte capsule to be used in tumor therapy, which could notably improve the therapeutic efficacy of PTX while reducing its side effects.

Microfluidic preparation and optimization of sorafenib-loaded poly(ethylene glycol-block-caprolactone) nanoparticles for cancer therapy applications

The use of amphiphilic block copolymers to generate colloidal delivery systems for hydrophobic drugs has been the subject of extensive research, with several formulations reaching the clinical development stages. However, to generate particles of uniform size and morphology, with high encapsulation efficiency, yield and batch-to-batch reproducibility remains a challenge, and various microfluidic technologies have been explored to tackle these issues. Herein, we report the development and optimization of poly(ethylene glycol)-block-(ε-caprolactone) (PEG-b-PCL) nanoparticles for intravenous delivery of a model drug, sorafenib. We developed and optimized a glass capillary microfluidic nanoprecipitation process and studied systematically the effects of formulation and process parameters, including different purification techniques, on product quality and batch-to-batch variation. The optimized formulation delivered particles with a spherical morphology, small particle size (dH < 80 nm), uniform size distribution (PDI < 0.2), and high drug loading degree (16 %) at 54 % encapsulation efficiency. Furthermore, the stability and in vitro drug release were evaluated, showing that sorafenib was released from the NPs in a sustained manner over several days. Overall, the study demonstrates a microfluidic approach to produce sorafenib-loaded PEG-b-PCL NPs and provides important insight into the effects of nanoprecipitation parameters and downstream processing on product quality.

Redox-Sensitive multifunctional hyaluronic acid-based nanomicelles with Fine-controlled anticancer drug release

A significant contributor to cancer-related death globally is metastatic breast cancer. To reduce death rates, tumor-specific penetration and triggered drug release are crucial. Herein, targeted intracellular doxorubicin (Dox) delivery system was effectively prepared based on redox-sensitive hyaluronic acid-palmitoyl (HA-ss-PA) copolymers. The amphiphilic copolymers self-assembled into nano and showed outstanding drug-loading capacities and encapsulation efficiency for Dox. Micelles were stable under physiological conditions, but they quickly disintegrated in the presence of a reducing agent. The intracellular location of the fluorescent probe rhodamine b demonstrated that HA-ss-PA micelles are an efficient approach for drug delivery in breast cancer cells. Based on flow cytometry and live/dead assay, observations indicated that micelles induce apoptosis in both MCF-7 and MDA-MB-231 cells. In vivo evaluation in tumor-bearing mice confirmed that HA-ss-PA micelles exhibited excellent tumor-targeting activity. These findings imply that redox-sensitive HA-ss-PA micelles are promising candidates for use as intracellular delivery systems for hydrophobic anti-cancer drugs.

Construction of pH-responsive nanoplatform from stable magnetic nanoparticles for targeted drug delivery and intracellular imaging

Currently, developing responsive hydrophobic drug delivery systems centered on magnetic nanoparticles is a promising approach for the efficient delivery of hydrophobic drugs to living cells. Here, an efficacious designed strategy was proposed to construct pH-responsive nanoplatform for targeted hydrophobic drug delivery based on the formation of surface-anchored targeting molecules on the surface of Fe3O4 @C via single electron transfer living radical polymerization (SET-LRP) method. First, we prepared polymer-modified Fe3O4 @C using 4-vinylphenylboronic acid (VB) and polyethylene glycol methyl ether methacrylate (PEGMA) as polymerized monomers and confirmed that Fe3O4 @C-VB-PEGMA had high biocompatibility and low cytotoxicity. Next, we prepared curcumin-containing Fe3O4 @C-VB-PEGMA-Cur nanoplatform with an encapsulation efficiency for Cur as high as 67.7%. Furthermore, the nanoplatform not only displayed pH-responsive release behaviors of Cur under different pH values (pH=7.2, 6.5, 5.4), but also can be effectively targeted into HepG2 cells. More importantly, the nanoplatform also exhibited effectively inhibiting the growth of HepG2 cells and continuously intracellular imaging by the targeted releasing of loaded Cur. It is envisaged that these findings are a step forward in the construction of pH-responsive platform as a tool for clinical hydrophobic drug delivery.

Current development of cabazitaxel drug delivery systems.

The second-generation taxane cabazitaxel has been clinically approved for the treatment of metastatic castration-resistant prostate cancer after docetaxel failure. Compared with the first-generation taxanes paclitaxel and docetaxel, cabazitaxel has potent anticancer activity and is less prone to drug resistance due to its lower affinity for the P-gp efflux pump. The relatively high hydrophobicity of cabazitaxel and the poor aqueous colloidal stability of the commercial formulation, following its preparation for injection, presents opportunities for new cabazitaxel formulations with improved features. This review provides an overview of cabazitaxel drug formulations and hydrophobic taxane drug delivery systems in general, and particularly focuses on emerging cabazitaxel delivery systems discovered in the past 5 years. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Combined Shikonin-Loaded MPEG-PCL Micelles Inhibits Effective Transition of Endothelial-to-Mesenchymal Cells.

IntroductionShikonin is well known for its anti-inflammatory activity in cardiovascular diseases. However, the application of shikonin is limited by its low water solubility and poor bioavailability. Methoxy poly (ethylene glycol)-b-poly (ε-caprolactone) (MPEG-PCL) is considered a promising delivery system for hydrophobic drugs. Therefore, in this study, we prepared shikonin-loaded MPEG-PCL micelles and investigated their effect on endothelial-to-mesenchymal transition (EndMT) induced by inflammatory cytokines.MethodsShikonin was encapsulated in MPEG-PCL micelles using an anti-solvent method and the physiochemical characteristics of the micelles (particle size, zeta potential, morphology, critical micelle concentration (CMC), drug loading and encapsulation efficiency) were investigated. Cellular uptake of micelles in human umbilical vein endothelial cells (HUVECs) was evaluated using fluorescence microscopy. In vitro EndMT inhibition was explored in HUVECs by quantitative real-time PCR analysis.ResultsThe average particle size of shikonin-loaded MPEG-PCL micelles was 54.57±0.13 nm and 60 nm determined by dynamic light scattering and transmission electron microscopy, respectively. The zeta potential was −6.23±0.02 mV. The CMC of the micelles was 6.31×10−7mol/L. The drug loading and encapsulation efficiency were 0.88±0.08% and 43.08±3.77%, respectively. The MPEG-PCL micelles significantly improved the cellular uptake of cargo with low water solubility. Real-time PCR analysis showed that co-treatment with TNF-α and IL-1β successfully induced EndMT in HUVECs, whereas this process was significantly inhibited by shikonin and shikonin-loaded MPEG-PCL micelles, with greater inhibition mediated by the shikonin-loaded MPEG-PCL micelles.ConclusionShikonin-loaded MPEG-PCL micelles significantly improved the EndMT-inhibiting effect of the free shikonin. MPEG-PCL is suitable for use more generally as a lipophilic drug carrier.

Thermosensitive core-rigid micelles of monomethoxy poly(ethylene glycol)-deoxy cholic acid

BackgroundThermosensitive micelles with rigid cores that exhibit a reversible lower critical solution temperature at 30–35 °C can be applied for drug delivery.MethodHydrophilic monomethoxy poly(ethylene glycol) was conjugated to hydrophobic deoxycholic acid to prepare monomethoxy poly(ethylene glycol)-deoxycholic acid (mPEG-DC). Micelle formation and thermosensitive solution behavior were studied using various methods, including hydrophobic dye solubilization, transmission electron microscopy, dynamic light scattering, turbidity measurement, microcalorimetry, and 1H-NMR spectroscopy. Drug release from the thermosensitive micelles was demonstrated using estradiol, a model drug.ResultsThe mPEG-DC formed micelles with a critical micelle concentration of 0.05 wt.% and an average size of 15 nm. Aqueous mPEG-DC solutions exhibit a lower critical solution temperature (LCST) that is independent of concentration and reversible over heating and cooling cycles. The LCST transition is an entropically driven process involving dehydration of the PEG shell. The thermosensitive mPEG-DC micelles with rigid DC cores were applied as an estradiol delivery system in which estradiol was released, without initial burst, over the 16 days in a diffusion-controlled manner.ConclusionsThis study suggests that mPEG-DCs form thermosensitive micelles with rigid cores that can function as an excellent diffusion-controlled hydrophobic drug delivery system without initial burst release.Graphical Thermosensitive core-rigid micelles of monomethoxy poly(ethylene glycol)-deoxy cholic acid