Thermoresponsive Pluronic® F127 (PL) gels in water were investigated through rheological tests in different shear conditions. The gel strength was tuned with the addition of 1% polysaccharide solution. In the presence of xanthan gum (XG), the viscoelastic behavior of PL-based hydrogels was improved in aqueous environment, but the rheological behavior was less changed with the addition of XG in PBS solutions, whereas in the presence of 0.1 M NaCl, the viscoelastic parameters decreased. PL micellar networks exhibited a self-healing ability, recovering their initial structure after applying cycles of high strain. The rheological characteristics of the PL hydrogel changed with the addition of 1% polysaccharides (xanthan gum, alginate, κ-carrageenan, gellan, or chitosan). PL/polysaccharide systems form temperature-responsive hydrogels with shear thinning behavior, yield stress, and self-healing ability, being considered a versatile platform for injectable biomaterials or bioinks. Thus, in the presence of xanthan gum in aqueous medium, the gel strength was improved after applying a high strain (the values of elastic modulus increased). The other investigated natural polymers induced specific self-healing behaviors. Good performances were observed with the addition of gellan gum, alginate, and κ-carrageenan, but for high values of strain, the ability to recover the initial structure decreased. A modest self-healing behavior was observed in the presence of chitosan and xanthan gum dissolved in NaCl solution.

BACKGROUND: Streptococcus mutans and Candida albicans can colonize the teeth, the oral cavity as biofilm and can cause oral infections. Thus, strategies to prevent and control oral biofilms are requested. The present study aims the development and characterization of methylene blue (MB)-loaded polymeric micelles for antimicrobial photodynamic therapy (aPDT) against Streptococcus mutans and Candida albicans biofilms METHODS: MB-loaded polymeric micelles were produced and characterized by particle size, polydispersity index, morphology, zeta potential, stability, MB release profile, and antimicrobial effect against S. mutans and C. albicans biofilms.
RESULTS: MB-loaded polymeric micelles showed a reduced particle size, moderate polydisperse profile, spherical and neutral shape, which demonstrated to be promising features to allow micelles penetration into biofilms. Antimicrobial effect against bacterial and yeast biofilms was demonstrated once MB was irradiated by light under 660 nm (aPDT). Furthermore, MB-loaded polymeric micelles showed significant inhibition of S. mutans and C. albicans biofilms. Furthermore, the treatment with MB-micelles incubated with high pre-incubation times (15 and 30 min) were more effective than 5 min. It can be explained by the time required for this nanosystem to penetrate the innermost layer of biofilms and release MB for aPDT.
CONCLUSIONS: MB-loaded polymeric micelles can effectively decrease the bacteria and yeast viability and it may cause positive impacts in the clinical practice. Thus, the developed formulation showed potential in the treatment to remove oral biofilms, but clinical studies are needed to confirm its potential.

Ocular health may strongly benefit from the supply of antioxidant agents that counteract free radicals and reactive oxygen species responsible for long-term eye diseases. Additionally, natural antioxidants like resveratrol can inhibit bacteria growth and restore natural microbiota. However, their use is hindered by limited solubility, fast degradation, and low ocular permeability. This work aimed to overcome these limitations by preparing single and mixed micelles of Pluronic® F127 and casein that serve as resveratrol nanocarriers. Single and mixed (0.1 % casein) micelles (0.0 to -17.0 mV; 2.4 to 32.7 nm) increased 50-fold resveratrol solubility, remained stable for one month at 4 °C, withstood fast dilution, underwent sol-to-gel transitions in the 23.9-27.1 °C range, and exhibited potent antioxidant properties. All formulations successfully passed the HET-CAM assay but showed Pluronic®-casein dose-dependent toxicity in the zebrafish embryo model. Resveratrol-loaded single and mixed micelles (10-15 mM Pluronic® F127) displayed antimicrobial activity against S. aureus and P. aeruginosa. The micelles favored resveratrol accumulation in cornea and sclera, but mixed micelles showed larger lag times and provided lower amount of resveratrol permeated through sclera. In vivo (rabbit) tests confirmed the safety of resveratrol-loaded single micelles and their capability to supply resveratrol to anterior and posterior eye segments.

This study aimed to develop and evaluate thermoresponsive in situ microgels for the local ocular delivery of prednisolone (PRD) (PRD microgels) to improve drug bioavailability and prolong ocular drug residence time. Lipid nanosystems of PRD microemulsions (PRD-MEs) were prepared and evaluated at a drug concentration of 0.25-0.75%. PRD microgels were prepared by incorporating PRD-MEs into 10 and 12% Pluronic® F127 (F127) or combinations of 12% F127 and 1-10% Kolliphor®P188 (F68). PRD microgels were characterized for physicochemical, rheological, and mucoadhesive properties, eye irritation, and stability. Results showed that PRD-MEs were clear, miscible, thermodynamically stable, and spherical with droplet size (16.4 ± 2.2 nm), polydispersity index (0.24 ± 0.01), and zeta potential (-21.03 ± 1.24 mV). The PRD microgels were clear with pH (5.37-5.81), surface tension (30.96-38.90 mN/m), size, and zeta potential of mixed polymeric micelles (20.1-23.9 nm and -1.34 to -10.25 mV, respectively), phase transition temperature (25.3-36 °C), and gelation time (1.44-2.47 min). The FTIR spectra revealed chemical compatibility between PRD and microgel components. PRD microgels showed pseudoplastic flow, viscoelastic and mucoadhesive properties, absence of eye irritation, and drug content (99.3 to 106.3%) with a sustained drug release for 16-24 h. Microgels were physicochemically and rheologically stable for three to six months. Therefore, PRD microgels possess potential vehicles for local ocular delivery.

In this work, the miscibility of blends of thermoplastic Achira Starch (AS) and polylactic acid (PLA) was evaluated, assisted by Pluronic® F127 an amphiphilic triblock copolymer that acts as a surfactant and promotes the reduction of surface tension among AS and PLA in solution by emulsion stabilization. Different formulations of AS/PLA blends were obtained at 75:25, 50:50, and 25:75 containing 0 %, 4 %, and 8 % of Pluronic® F127, and glycerol was used as a plasticizer. Solvent casting was the method used to obtain blended polymeric films, which were characterized by Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), Thermogravimetric Analysis (TGA), differential scanning calorimetry (DSC) and wettability by contact angle measurements. The results demonstrate that miscibility of PLA in AS or vice versa was achieved. The stability of emulsion and posterior drying of the different formulations allows the production of films for packaging, pharmaceutical, or biomedical applications.

Carvedilol (CAR) is a widely studied, beta and alpha-1 blocker, antihypertensive drug due to its poor water solubility and low oral bioavailability (25-35%). The aim of this work is to improve poor water solubility and the pharmacokinetic parameters of carvedilol by using an optimized and self-assembly prepared micelle formulation. Optimized micelle formulation composed of Pluronic® F127, D-α-tocopheryl polyethylene glycol 1000 succinate, L-cysteine HCl in a ratio of 4:3:3. Micellar size, polydispersity index, zeta potential, morphology, critical micelle concentration, thermal behaviors, in-vitro dissolution of micelles and pharmacokinetic parameters in rats were characterized in this study. Carvedilol aqueous solubility increased (up to 271-fold) as a result of its encapsulation within a mixed micelle formulation. The measured micellar sizes of blank and carvedilol loaded mixed micelles are lower than 30 nm with size distributions of 26.69 ± 2.93 nm and 24.16 ± 4.89 nm, respectively. Transmission electron microscopy revealed that the micelles were spherically shaped. There is a significant enhancement of carvedilol dissolution compared to commercially available tablet formulation (f2 < 50). The in-vivo test demonstrated that the t1/2 and AUC0-∞ values of micelles were approximately 10.89- and 2.65-fold greater than that of the commercial tablets, respectively. Based on our study, bring such applications into being may provide effective new drugs for treatment armamentarium of cardiovascular diseases and hypertension in near future.

The ability to formulate cubosomes and hexosomes with a single lipid by changing only the colloidal stabiliser presents a unique opportunity to directly compare the biological performance of these uniquely structured nanoparticles. This was explored here via the encapsulation and brain delivery of a model anti-seizure drug, phenytoin, in selachyl alcohol cubosomes and hexosomes. Nanoparticles were prepared with Pluronic® F127 or Tween 80® as the stabiliser and characterised. The internal nanostructure of nanoparticles shifted from hexosomes when using Pluronic® F127 as the stabiliser to cubosomes when using Tween 80® and was conserved following loading of phenytoin, with high encapsulation efficiencies (>97%) in both particle type. Cytotoxicity towards brain endothelial cells using the hCMEC/D3 line was comparable regardless of stabiliser type. Finally, in vivo brain delivery of phenytoin encapsulated in cubosomes and hexosomes after intravenous administration to rats was studied over a period of 60 min, showing cubosomes to be superior to hexosomes, both in terms of brain concentrations and brain to plasma ratio. While the role of stabiliser and/or internal nanostructure remains to be conclusively determined, this study is the first in vivo comparison of cubosomes and hexosomes for the delivery of a therapeutic drug molecule across the BBB and into the brain.

The aim of this study was the development of hard-cellulose capsules containing cefpodoxime proxetil (CEF) (BCS Class II) loaded novel Pluronic® F127 (P127)/Polyvinylpyrrolidone K30 (PVP) solid dispersions (SDs) using ultrasonic probe induced solvent-lyophilization method for effective antibacterial treatment by means of improved saturated aqueous solubility, dissolution rate, reduced particle size, and wettability. SDs were evaluated for physical and solid-state analyses. The solubility of pure CEF was calculated as 0.269 ± 0.005 mg/mL, SDs formulated with P127/PVP exhibited increased solubility from 3.5- to 8-fold. Molecular distribution of CEF in SDs and formation of CEF loaded amorphous polymeric network were confirmed with morphological study, thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), and 1H-NMR studies. Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), and Klebsiella pneumoniae (ATCC 700603) were used to investigate the antibacterial effectiveness of the SDs. The minimum inhibitory concentration (MIC) values of the P127/PVP SDs were found 2-8 times lower than the pure CEF. All SDs from hard-cellulose capsules exhibited significantly faster release than unprocessed CEF. The profiles of SDs and reference were detected to be dissimilar according to difference (f1) and similarity factor (f2). Hard-cellulose capsules containing CEF loaded P127/PVP SDs appear to be feasible alternative to commercially available CEF tablets for effective antibacterial therapy at lowest dose.

Bladder cancer has a high incidence and recurrence rate among patients worldwide. This study aimed to evaluate the cytotoxic activity of fractions of Sambucus nigra L. flower extracts on bladder carcinoma cells (T24 cells) and human fibroblast cells (MRC-5). The butanolic fraction (F-BuOH) was characterized by UPLC-DAD-MS/MS and nine flavonoids were identified. Rutin was the major compound. The cytotoxic activity of this fraction was observed in the T24 cells but not in MRC-5 cells, indicating selectivity. F-BuOH was incorporated in micellar solutions of Pluronic® F127 and cytotoxic effect for T24 cells was observed again. In vitro assay demonstrated a controlled release of the fraction from the micelles. The results obtained showed that flavonoids are the possible responsible for cytotoxic activity in bladder carcinoma cells. In addition, micellar solutions act together to increase the action of the butanolic fraction.

Acyclovir (ACV) is one of the most used antiviral drugs for the treatment of herpes simplex virus infections and other relevant mucosal infections caused by viruses. Nevertheless, the low water solubility of ACV limits both its bioavailability and antiviral performance. The combination of block copolymer micelles and cyclodextrins (CDs) may result in polypseudorotaxanes with tunable drug solubilizing and gelling properties. However, the simultaneous addition of various CDs has barely been investigated yet. The aim of this work was to design and characterize ternary combinations of Pluronic® F127 (PF127), αCD and βCD in terms of polypseudorotaxane formation, rheological behavior, and ACV solubilization ability and controlled release. The formation of polypseudorotaxanes between PF127 and the CDs was confirmed by FT-IR spectroscopy, X-ray diffraction, and NMR spectroscopy. The effects of αCD/βCD concentration range (0-7% w/w) on copolymer (6.5% w/w) gel features were evaluated at 20 and 37 °C by rheological studies, resulting in changes of the copolymer gelling properties. PF127 with αCD/βCD improved the solubilization of ACV, maintaining the biocompatibility (hen\'s egg test on the chorio-allantoic membrane). In addition, the gels were able to sustain acyclovir delivery. The formulation prepared with similar proportions of αCD and βCD provided a slower and more constant release. The results obtained suggest that the combination of Pluronic with αCD/βCD mixtures can be a valuable approach to tune the rheological features and drug release profiles from these supramolecular gels.