Mixed Polymeric Micelles Research Articles

Molecular Interactions of the Antimicrobial Peptide Tritrpticin with Mixed Nanoaggregates: A Fluorescence Spectroscopy Study.

Tritrpticin (TRP3) is a peptide belonging to the cathelicidin family and has a broad spectrum of antimicrobial activity. However, this class of biomolecules can be easily degraded in the body, making it necessary to use an efficient transport system. The ability to form stable nanostructures from the interaction of glycyrrhizin saponin with the pluronic polymer F127 was demonstrated, forming mixed biopolymeric micelles, highly promising as drug carriers. The present work sought to understand the physicochemical interaction of the antimicrobial peptide TRP3 with the mixed polymeric micelle made from pluronic F127 and the saponin glycyrrhizin. The interaction of tritrpticin with mixed nanostructured micelles was evaluated through fluorescence spectroscopy and fluorescence quenching with acrylamide. The experiments were performed at room temperature (25 ± 1°C), adopting an excitation wavelength set to 280 nm and emission between 300 and 500 nm, with a slit of 5 nm. The interaction of the cationic peptide tritrpticin with the mixed biopolymeric micelles was observed through the blue shift of the fluorescence emission to shorter wavelengths, proving the change of tryptophan to a more hydrophobic environment. Through the fluorescence suppression technique, it was possible to indicate the location of the peptide in the mixed micelles, proving tritrpticin to be partially inserted inside them. It was concluded that tritrpticin interacted with mixed nanostructured micelles, forming a promising system for biotechnological applications.

Gram Negative Biofilms: Structural and Functional Responses to Destruction by Antibiotic-Loaded Mixed Polymeric Micelles.

Biofilms are a well-known multifactorial virulence factor with a pivotal role in chronic bacterial infections. Their pathogenicity is determined by the combination of strain-specific mechanisms of virulence and the biofilm extracellular matrix (ECM) protecting the bacteria from the host immune defense and the action of antibacterials. The successful antibiofilm agents should combine antibacterial activity and good biocompatibility with the capacity to penetrate through the ECM. The objective of the study is the elaboration of biofilm-ECM-destructive drug delivery systems: mixed polymeric micelles (MPMs) based on a cationic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA35-b-PCL70-b-PDMAEMA35) and a non-ionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO100-b-PPO65-b-PEO100) triblock copolymers, loaded with ciprofloxacin or azithromycin. The MPMs were applied on 24 h pre-formed biofilms of Escherichia coli and Pseudomonas aeruginosa (laboratory strains and clinical isolates). The results showed that the MPMs were able to destruct the biofilms, and the viability experiments supported drug delivery. The biofilm response to the MPMs loaded with the two antibiotics revealed two distinct patterns of action. These were registered on the level of both bacterial cell-structural alterations (demonstrated by scanning electron microscopy) and the interaction with host tissues (ex vivo biofilm infection model on skin samples with tests on nitric oxide and interleukin (IL)-17A production).

Oral and tumor-targeting mixed micelles based on pegylated biotin and chitosan-based conjugate for breast cancer treatment

Oral drug delivery with tumor-targeting treatment persists as a challenge. In this study, a mixed polymeric micelle (PM) delivery system was designed to overcome the barriers to oral administration for tumor-targeting delivery of paclitaxel (PTX) for breast cancer treatment. D-α-Tocopheryl polyethylene glycol 1000 succinate-modified carboxymethyl chitosan-rhein (TCR) conjugate and Biotin-polyethylene glycol 2000-Biotin (BPB) conjugate were mixed to form TCR-BPB PMs. The particle size and polydispersity index of optimized PTX-loaded TCR-BPB PMs (PTX/TCR-BPB PMs) was 195.90 ± 7.63 nm and 0.08 ± 0.00, with a drug-loading capacity of 41.94 ± 2.47 %. In simulated gastroenteric fluid and blood environments, the PMs presented a sustained-release manner. PTX/TCR-BPB PMs were taken up by Caco-2 and 4T1 cells and displayed strong cytotoxicity in a time- and concentration-dependent manner. PTX/TCR-BPB PMs significantly improved intestinal absorption of PTX. The pharmacokinetics, tissue distribution, and in vivo imaging indicated that PTX/TCR-BPB PMs could enhance oral bioavailability of PTX, prolong the retention time of PTX in the blood, and enhance PTX tumor-targeting ability. PTX/TCR-BPB PMs enhance the antitumor efficacy of PTX and reduce its toxicity in normal organs. Therefore, TCR-BPB PMs are expected to serve as delivery carriers for the oral and tumor-targeting delivery of hydrophobic antitumor drugs.

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.

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.

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.

Mixed Micellar Gel of Poloxamer Mixture for Improved Solubilization of Poorly Water-Soluble Ibuprofen and Use as Thermosensitive In Situ Gel.

The aqueous solution of binary mixtures of amphiphilic copolymers is a potential platform for fabricating mixed polymeric micelles for pharmaceutical applications, particularly in developing drug delivery depots for a poorly water-soluble compound. This study fabricated and investigated binary mixtures of poloxamer 403 (P403) and poloxamer 407 (P407) at varying P403:P407 molar ratios to develop a vehicle for the poorly water-soluble compound, using ibuprofen as a model drug. The cooperative formation of mixed micelles was obtained, and the solubility of ibuprofen in the binary mixtures was enhanced compared to the solubility in pure water and an aqueous single P407 solution. The binary mixture with the P403:P407 molar ratio of 0.75:0.25 at a total polymer concentration of 19% w/v exhibited the temperature dependence of micellization and sol-to-gel characteristics of the thermosensitive mixed micellar gels. It possessed suitable micellization and gelation characteristics for in situ gelling systems. The release of ibuprofen from the thermosensitive mixed micellar depots was sustained through a diffusion-controlled mechanism. The findings can aid in formulating binary mixtures of P403 and P407 to achieve the desired properties of mixed micelles and micellar gels.

Polymeric Mixed Micelle-Loaded Hydrogel for the Ocular Delivery of Fexofenadine for Treating Allergic Conjunctivitis.

This study was designed to formulate a polymeric mixed micelle (PMM) formulation to sustainably release fexofenadine (FEX) to treat allergic conjunctivitis effectively. A 32 factorial design was employed where the studied factors were PL90G amount (X1) and Pluronic (F127 and P123) mixture ratio (X2), and the dependent variables were entrapment efficacy (EE, Y1, %), particle size (PS, Y2, nm), zeta potential (ZP, Y3, mV), and the percent of drug released after 6 h (Q6h, Y4, %). The optimized formula was blended with a hydrogel base to develop an FEX-PMM hydrogel, where the safety and efficiency of this hydrogel were evaluated using in vivo studies. The EE% of FEX-PMM ranged from 62.15 ± 2.75 to 90.25 ± 1.48%, the PS from 291.35 ± 6.43 to 467.95 ± 3.60 nm, the ZP from -5.41 ± 0.12 to -9.23 ± 0.23 mV, and the Q6h from 50.27 ± 1.11 to 95.38 ± 0.92%. The Draize test results confirmed the safety of the FEX-PMM hydrogel. Furthermore, the FEX-PMM hydrogel showed rapid recovery in animals with induced allergic conjunctivitis compared to the free drug hydrogel. These results assure PMM's capability to deliver FEX to the conjunctival surface in a sustained pattern, consequently achieving better therapeutic outcomes.

Innovations in Skin Cancer Nanotechnology: A Comprehensive Review.

Skin cancer is the most common type of cancer among white people, according to the World Health Organisation. The incidence of melanoma and non-melanoma skin cancers has increased to epidemic levels, making them the most widespread type of skin cancer. Melanoma is a very aggressive form of cancer, characterized by limited treatment choices due to multidrug resistance and an extremely low probability of patient survival. This article explores the various impediments and limitations associated with conventionally available treatments. Chemotherapy, radiation, immunotherapy, and targeted therapy are among the conventional treatments for melanoma; however, each of these approaches has several adverse reactions. Recently, there has been a focus on biological and pharmacological research on developing alternative, site-specific therapy approaches. Nanotechnology offers several benefits in this regard, with the potential to enhance the longevity of melanoma patients while minimizing adverse effects. Nanoparticles serve as effective drug carrier systems due to their capacity to improve the solubility of medications with low water solubility, modify pharmacokinetics, prolong drug half-life by reducing immunogenicity, boost bioavailability, and decrease drug metabolism. This article highlights recent advancements in utilizing several nanotechnological techniques, including solid lipid nanoparticles, nanostructured lipid carriers, liposomes, transferosomes, ethosomes, and nanoemulsion polymeric mixed micelles.

Dual drug-loaded polymeric mixed micelles for ovarian cancer: Approach to enhanced therapeutic efficacy of albendazole and paclitaxel.

Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug-loaded nanomicelle system comprising albendazole (ABZ) and paclitaxel (PTX), encapsulated in a novel carrier matrix of D-tocopheryl polyethylene glycol 1000 succinate vitamin E (TPGS), soluplus and folic acid. Our objective was to develop and optimize this nanoparticulate delivery system using solvent evaporation techniques to enhance the therapeutic efficacy against ovarian cancer. The formulation process involved pre-formulation, formulation, optimization, and comprehensive characterization of the micelles. Optimization was conducted through a 32 factorial design, focusing on the effects of polymer ratios on particle size, zeta potential, polydispersity index (PDI) and entrapment efficiency (%EE). The optimal formulation demonstrated improved dilution stability, as indicated by a critical micelle concentration (CMC) of 0.0015 mg/mL for the TPGS-folic acid conjugate (TPGS-FOL). Extensive characterization included differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FTIR). The release profile exhibited an initial burst followed by sustained release over 90 h. The cytotoxic potential of the formulated micelles was superior to that of the drugs alone, as assessed by MTT assays on SKOV3 ovarian cell lines. Additionally, invivo studies confirmed the presence of both drugs in plasma and tumour tissues, suggesting effective targeting and penetration. In conclusion, the developed TPGS-Fol-based nanomicelles for co-delivering ABZ and PTX show promising results in overcoming drug resistance, enhancing solubility, sustaining drug release, and improving therapeutic outcomes in ovarian cancer treatment.

Celastrol-loaded polymeric mixed micelles shows improved antitumor efficacy in 4 T1 bearing xenograft mouse model through spatial targeting

In this study, we have proposed a novel approach that combines hyaluronic acid (HA), folic acid (FA), and celastrol (CLS) within a polymeric micelle system (CLS-HF/MLs), offering a dual-action strategy against breast cancer. Polymeric mixed micelles were prepared through the thin-film hydration method, and comprehensive quality control parameters were established, encompassing particle size, polydispersity index, zeta potential, surface morphology, encapsulation efficiency, drug content, in vitro drug release, and storage stability assessment. The average particle size of CLS-HF/MLs micelles was found to be 120 nm and their drug loading and encapsulation efficiencies were 15.9 % and 89.52 %, respectively. The in vitro release data showed that the CLS-HF/MLs targeted mixed micelles displayed a prolonged release profile compared to the free drug. Additionally, the stability of the developed polymeric mixed micelles was maintained for up to 8 weeks of storage in terms of particle size and drug content. Furthermore, both flow cytometry and confocal laser scanning microscopy studies indicated a significant enhancement in the cellular uptake efficiency and cytotoxicity of CLS-HF/MLs mixed micelles against MCF-7 cell line. In terms of pharmacokinetic analysis, the half-life and AUC values of CLS-HF/MLs mixed micelles were found to be approximately 4.71- and 7.36-folds higher than the values of free drug (CLS), respectively. The CLS-HF/MLs micelles exhibited remarkable antitumor efficacy (almost complete ablation of the 4 T1-cell bearing tumor xenografts mouse model) due to the dual receptor (CD44 and folate) targeting effects with minimal side effects. When considering the cumulative findings of our present research, it becomes evident that mixed micelles designed for chemotherapy offer a promising and potentially effective therapeutic avenue for the treatment of breast cancer

Tailoring micellar nanocarriers for pemetrexed in breast cancer: design, fabrication and in vitro evaluation.

Aim: To investigate the pemetrexed encapsulated polymeric mixed micelles (PMMs) against breast cancer treatment.Methods: We meticulously optimized the formulation and conducted extensive characterizations, including photon correlation spectroscopy for micellization, advanced analytical techniques and in vitro cell line assessments.Results: The PMM exhibited favorable characteristics, with a spherical morphology, hydrodynamic particle size of 19.58±0.89nm, polydispersity index of 0.245±0.1, and a surface charge of -9.70±0.61mV. Encapsulation efficiency and drug payload reached 96.16±0.37% and 4.5±0.32%, respectively. Cytotoxicity analysis indicated superior efficacy of the PMM over the drug solution.Conclusion: The PMM formulation exhibited controlled release of the drug, and demonstrated enhanced cytotoxicity against breast cancer cells, highlighting its therapeutic promise.

Modulatory Effect of Erucin and Its Polymeric Mixed Micelles on 3-nitropropionic Acid-induced Neurodegeneration (P10-3.009)

Modulatory Effect of Erucin and Its Polymeric Mixed Micelles on 3-nitropropionic Acid-induced Neurodegeneration (P10-3.009)

Phyto-cosmeceutical gel containing curcumin and quercetin loaded mixed micelles for improved anti-oxidant and photoprotective activity

Ultra Violet radiations induced skin damage and associated skin disorders are a widespread concern. The consequences of sun exposure include a plethora of dermal conditions like aging, solar urticaria, albinism and cancer. Sunscreens provide effective protection to skin from these damages. Besides FDA approved physical and chemical UV filters, phytoconstituents with their multi functionalities are emerging as frontrunners in Therapy of skin disorders. Objective of this study was to develop novel phyto-dermal gel (PDG) with dual action of sun protection and antioxidant potential using polymeric mixed micelles (PMMs) are nanocarriers. PMMs of Pluronic F127 and Pluronic F68 loaded with curcumin and quercetin were optimized by 32 factorial designs. Responses studied were vesicle size, SPF, entrapment efficiency of curcumin and quercetin and antioxidant activity. Droplet size ranged from 300 to 500 nm with PDI in between 0.248 and 0.584. Combination of curcumin and quercetin showed enhanced sun protection and antioxidant activity. Pluronics played a significant positive role in various parameters. In present studies vesicle size of factorial batches was found to be between 387 and 527 nm, and SPF was found to be between 18.86 and 28.32. Transmission electron microscopy revealed spherical morphology of micelles. Optimized micelles were incorporated into Carbopol 940. Optimized PDG was evaluated for pH, drug content, spreadability, rheology, syneresis, ex vivo permeation, and skin retention. Hysteresis loop in the rheogram suggested thixotropy of PDG. Syneresis for gels from day 0–30 days was found to be between 0% and 12.46% w/w. SPF of optimized PDG was 27±0.5. Optimized PDG showed no signs of erythema and edema on Wistar rats. PMMs thus effectively enhanced antioxidant and skin protective effect of curcumin and quercetin.

Preparation, Optimization and In Vitro Characterization of Fluticasoneloaded Mixed Micelles Based on Stearic Acid-g-chitosan as a Pulmonary Delivery System.

The primary objective of this study was to optimize formulation variables and investigate the in vitro characteristics of fluticasone propionate (FP)-loaded mixed polymeric micelles, which were composed of depolymerized chitosan-stearic acid copolymer (DC-SA) in combination with either tocopheryl polyethylene glycol succinate or dipalmitoylphosphatidylcholine for pulmonary drug delivery. A D-optimal design was employed for the optimization procedure, considering lipid/ polymer ratio, polymer concentration, drug/ polymer ratio, and lipid type as independent variables. Dependent variables included particle size, polydispersion index, zeta potential, drug encapsulation efficiency, and loading efficiency of the polymeric micelles. Additionally, the nebulization efficacy and cell viability of the optimal FP-loaded DC-SA micellar formulations were evaluated. The mixed polymeric micelles were successfully prepared with properties falling within the desired ranges, resulting in four optimized formulations. The release of FP from the optimal systems exhibited a sustained release profile over 72 hours, with 70% of the drug still retained within the core of the micelles. The nebulization efficiency of these optimal formulations reached up to 63%, and the fine particle fraction (FPF) ranged from 41% to 48%. Cellular viability assays demonstrated that FP-loaded DC-SA polymeric micelles exhibited lower cytotoxicity than the free drug but were slightly more cytotoxic than empty mixed micelles. In conclusion, this study suggests that DC-SA/ lipid mixed micelles have the potential to serve as effective carriers for nebulizing poorly soluble FP.

Retraction: Development and optimization of TPGS/P84 mixed polymeric micelles: enhanced stability and anticancer effect of paclitaxel against tumor therapy

Dear Editor, In our subsequent study after the receipt of the article, it was found that the P84Ms carrier had certain cytotoxicity. As can be seen from the Figure 1 and Figure 2, compared with the cells in the control group, after incubation with different prepare preparations, the single carrier group Micelles-Blank and Mixed Micelles-Blank could inhibit the growth of the cells. However, the cytotoxicity data in the paper did not set Micelles-Blank and Mixed Micelles-Blank groups, which was also an oversight of our design at that time. Hence it is hard to say whether the therapeutic effect of the preparation is due to the toxicity of the carrier or the therapeutic effect of the drug in this article Therefore, the statement in the article that the carrier is safe and effective may be wrong. So the article needs to be withdrawn, and we will further modify the carrier in the future to reduce its toxicity.

An approach for an enhanced anticancer activity of ferulic acid-loaded polymeric micelles via MicroRNA-221 mediated activation of TP53INP1 in caco-2 cell line

Ferulic acid (FA) has powerful antioxidant and antitumor activities, but it has low bioavailability owing to its poor water solubility. Our aim is to formulate polymeric mixed micelles loaded with FA to overcome its poor solubility and investigate its potential anticancer activity via miRNA-221/TP53INP1 axis-mediated autophagy in colon cancer. A D-optimal design with three factors was used for the optimization of polymeric mixed micelles by studying the effects of each of total Pluronics mixture (mg), Pluronic P123 percentage (%w/w), and drug amount (mg) on both entrapment efficiency (EE%) and particle size. The anticancer activity of FA and Tocopheryl polyethylene glycol 1000 succinate (TPGS) mixed micelles formula (O2) was assessed by MTT and flow cytometry. O2 showed an EE% of 99.89%, a particle size of 13.86 nm, and a zeta potential of − 6.02 mv. In-vitro drug release studies showed a notable increase in the release rate of FA from O2, as compared to the free FA. The (IC50) values for FA from O2 and free FA were calculated against different cell lines showing a prominent IC50 against Caco-2 (17.1 µg/ml, 191 µg/ml respectively). Flow cytometry showed that FA caused cell cycle arrest at the G2/M phase in Caco-2. RT-PCR showed that O2 significantly increased the mRNA expression level of Bax and CASP-3 (4.72 ± 0.17, 3.67 ± 0.14), respectively when compared to free FA (2.59 ± 0.13, 2.14 ± 0.15), while miRNA 221 levels were decreased by the treatment with O2 (0.58 ± 0.02) when compared to free FA treatment (0.79 ± 0.03). The gene expression of TP53INP1 was increased by the treatment with O2 compared to FA at P < 0.0001. FA-loaded TPGS mixed micelles showed promising results for enhancing the anticancer effect of FA against colorectal cancer, probably due to its enhanced solubility. Thus, FA-loaded TPGS mixed micelles could be a potential therapeutic agent for colorectal cancer by targeting miRNA-221/TP53INP1 axis-mediated autophagy.

Mixed Pluronic/lecithin micelles formulation for oral bioavailability of candesartan cilexetil drug: in vitro characterization and in vivo pharmacokinetic investigations

Objective This study aimed to develop a mixed polymeric micelle formulation incorporating candesartan cilexetil (CAND) drug to enhance its oral bioavailability for the better treatment of hypertension. Methods A Box–Behnken design was utilized to optimize the CAND-incorporated mixed polymeric micelles formulation (CAND-PFLC) consisting of Pluronics (P123 and F68) and lecithin (LC). The optimized CAND-PFLC micelles formulation was characterized for size, shape, zeta potential, polydispersity index (PDI), and entrapment efficiency (%EE). An in vitro release study, ex vivo permeability investigation, and an in vivo pharmacokinetic analysis were carried out to evaluate the performance of the formulation. Results The optimized CAND-PFLC micelles formulation demonstrated a spherical shape, a particle size of 44 ± 2.03 nm, a zeta potential of −7.07 ± 1.39 mV, a PDI of 0.326 ± 0.06, and an entrapment efficiency of 87 ± 3.12%. The formulation exhibited excellent compatibility, better stability, and a noncrystalline nature. An in vitro release study revealed a faster drug release of 7.98% at gastric pH in 2 hrs and 94.45% at intestinal pH within 24 hrs. The ex vivo investigation demonstrated a significantly enhanced permeability of CAND, with 94.86% in the micelle formulation compared to 9.03% of the pure drug. In vivo pharmacokinetic analysis showed a 4.11-fold increase in oral bioavailability of CAND compared to the marketed formulation. Conclusion The CAND-PFLC mixed micelle formulation demonstrated improved performance compared to pure CAND, indicating its potential as a promising oral drug delivery system for the effective treatment of hypertension.

Inhalation of taraxasterol loaded mixed micelles for the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal lung disease characterized by pulmonary inflammation, oxidative stress, and excessive extracellular matrix (ECM) deposition. Current anti-fibrotic drugs for IPF treatment in the clinic lack selectivity and demonstrate unsatisfactory efficacy, highlighting the urgent necessity for a novel therapeutic strategy. Taraxasterol (TA), which has biological activities against lung injury induced by various factors, is a potential anti-IPF drug due to its anti-inflammatory, antioxidant and lung-protective effects. However, the protective effect of TA on IPF has not been confirmed, and its clinical application is limited due to its poor aqueous solubility. In this study, we demonstrated that TA could inhibit epithelial-mesenchymal transition (EMT) and migration of A549 cells by inhibiting the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. To improve the aqueous solubility and pulmonary administration performance of TA, we prepared TA loaded methoxy poly(ethylene glycol)-poly(d,l-lactide) (mPEG-PLA)/d-α-tocopheryl polyethylene glycol succinate (TPGS) mixed polymeric micelles (TA-PM). Then a MicroSprayerⓇ Aerosolizer was used to deliver TA-PM once every two days for three weeks to evaluate their therapeutic effects on bleomycin (BLM)-induced IPF mice. Our results demonstrated that inhaled TA-PM significantly inhibited BLM-induced inflammation, oxidative stress and fibrosis in lung tissue. Furthermore, TA-PM exhibited high pulmonary deposition and retention by pulmonary administration, along with a favorable safety profile. Overall, this study emphasizes the potential of inhaled TA-PM as a promising treatment for IPF, providing a new opportunity for their clinical application.

Folic acid grafted mixed polymeric micelles as a targeted delivery strategy for tamoxifen citrate in treatment of breast cancer

The objective of this study was to develop folic acid (FA) grafted mixed polymeric micelles loaded with Tamoxifen citrate (TMXC) to enhance its antitumor activity in breast tissues. The conjugated folic acid Pluronic 123 (FA-P123) was prepared using carbonyl diimidazole cross-linker chemistry and confirmed using FTIR and 1HNMR. TMXC-loaded P123/P84 (unconjugated) and TMXC-loaded FA-P123/P84 (conjugated) micelles were examined for encapsulation efficiency, particle size, surface charge, in vitro drug release, cytotoxic effect, and cellular uptake by a breast cancer cell line. The conjugated TMXC-loaded micelle exhibited a nanoparticle size of 35.01 ± 1.20 nm, a surface charge of—20.50 ± 0.95 mV, entrapped 87.83 ± 5.10% and released 67.58 ± 2.47% of TMXC after 36 h. The conjugated micelles exhibited a significantly higher cellular uptake of TMXC by the MCF-7 cell line and improved in vitro cytotoxicity by 2.48 folds compared to the TMXC-loaded unconjugated micelles. The results of in vivo studies indicated that TMXC-loaded FA-P123/P84 has a potential antitumor activity, as revealed by a significant reduction of tumor volume in tumor-bearing mice compared to TMXC-loaded unconjugated micelles. In conclusion, the obtained results suggested that conjugated FA-P123/P84 micelles could be an encouraging carrier for the treatment of breast cancer with TMXC.Graphical abstract