A "Ferroptosis-Amplifier" Hydrogel for Eliminating Refractory Cancer Stem Cells Post-lumpectomy.

The unique "Iron Addiction" feature of cancer stem cells (CSCs) with tumorigenicity and plasticity generally contributes to the tumor recurrence and metastasis after a lumpectomy. Herein, a novel "Ferroptosis Amplification" strategy is developed based on integrating gallic acid-modified FeOOH (GFP) and gallocyanine into Pluronic F-127 (F127) and carboxylated chitosan (CC)-based hydrogel for CSCs eradication. This "Ferroptosis Amplifier" hydrogel is thermally sensitive and achieves rapid gelation at the postsurgical wound in a breast tumor model. Specifically, gallocyanine, as the Dickkopf-1 (DKK1) inhibitor, can decrease the expression of SLC7A11 and GPX4 and synergistically induce ferroptosis of CSCs with GFP. Encouragingly, it is found that this combination suppresses the migratory and invasive capability of cancer cells via the downregulation of matrix metalloproteinase 7 (MMP7). The in vivo results further confirm that this "Ferroptosis Amplification" strategy is efficient in preventing tumor relapse and lung metastasis, manifesting an effective and promising postsurgical treatment for breast cancer.

Analysis of the impact of pluronic acid on the thermal stability and infectivity of AAV6.2FF.

BACKGROUND: The advancement of AAV vectors into clinical testing has accelerated rapidly over the past two decades. While many of the AAV vectors being utilized in clinical trials are derived from natural serotypes, engineered serotypes are progressing toward clinical translation due to their enhanced tissue tropism and immune evasive properties. However, novel AAV vectors require formulation and stability testing to determine optimal storage conditions prior to their use in a clinical setting. RESULTS: Here, we evaluated the thermal stability of AAV6.2FF, a rationally engineered capsid with strong tropism for lung and muscle, in two different buffer formulations; phosphate buffered saline (PBS), or PBS supplemented with 0.001% non-ionic surfactant Pluronic F68 (PF-68). Aliquots of AAV6.2FF vector encoding the firefly luciferase reporter gene (AAV6.2FF-ffLuc) were incubated at temperatures ranging from -20°C to 55°C for varying periods of time and the impact on infectivity and particle integrity evaluated. Additionally, the impact of several rounds of freeze-thaw treatments on the infectivity of AAV6.2FF was investigated. Vector infectivity was measured by quantifying firefly luciferase expression in HEK 293 cells and AAV particle integrity was measured by qPCR quantification of encapsidated viral DNA. CONCLUSIONS: Our data demonstrate that formulating AAV6.2FF in PBS containing 0.001% PF-68 leads to increased stability and particle integrity at temperatures between -20℃ to 21℃ and protection against the destructive effects of freeze-thaw. Finally, AAV6.2FF-GFP formulated in PBS supplemented with 0.001% PF-68 displayed higher transduction efficiency in vivo in murine lung epithelial cells following intranasal administration than vector buffered in PBS alone further demonstrating the beneficial properties of PF-68.

Modulation of macrophages by a phillyrin-loaded thermosensitive hydrogel promotes skin wound healing in mice.

BACKGROUND: Impaired wound healing in traumatic skin injuries remains a severe clinical challenge due to impaired re-vascularization, harmful bacteria infection, and inflammation dysregulation. Macrophages are recognized as prominent immune cells in tissue regeneration and wound healing. Consequently, the modulation of macrophages provides a promising therapeutic target for wound healing disorders. Here, we aimed to explore whether a novel constructed combination of thermosensitive hydrogel Pluronic F-127 (PF-127) and phillyrin (PH, the main active compound of forsythia suspensa) could improve skin wound healing. METHODS: Firstly, the biological effects of pH on the phenotype and inflammation of macrophages were assessed by flow cytometry and ELISA. The biocompatibility of the PF-127 plus PH combination was investigated on keratinocytes and red blood cells. The biological effect of PF-127/PH hydrogel on the migratory ability of keratinocytes in vitro was evaluated using the scratch and transwell migration assays. In addition,S. aureusandE. coliwere employed to test the antibacterial properties of the PF-127 plus PH combination. Finally, PF-127 plus PH scaffold was appliedto the full-thickness skin defect in mice. Histomorphological evaluation and immunochemistry were performed to explore the wound-healing activity of PF-127/PH hydrogel. RESULTS: PH can promote the polarization of macrophages from the M1 (pro-inflammatory) phenotype to the M2 (anti-inflammatory) phenotype. The PF-127/PH hydrogel was highly biocompatible and showed a potent stimulative effect on the migration of keratinocytesin vitro. The combination of PF-127 and PH exerted a pronounced antibacterial activity onS. aureusandE. coli in vitro.PF-127/PH hydrogel potently accelerates the healing of full-thickness skin defects by promoting skin cell proliferation, accelerating angiogenesis, and inhibiting inflammation. CONCLUSIONS: Our study suggests that PF-127/PH hydrogel has excellent potential for treating traumatic skin defects.

Lysosome-targeted ruthenium(II) complex encapsulated with pluronic® F-127 induces oncosis in A549 cells.

Transition metal complexes with characteristics of unique packaging in nanoparticles and remarkable cancer cell cytotoxicity have emerged as potential alternatives to platinum-based antitumor drugs. Here we report the synthesis, characterization, and antitumor activities of three new Ruthenium complexes that introduce 5-fluorouracil-derived ligands. Notably, encapsulation of one such metal complex, Ru3, within pluronic® F-127 micelles (Ru3-M) significantly enhanced Ru3 cytotoxicity toward A549 cells by a factor of four. To determine the mechanisms underlying Ru3-M cytotoxicity, additional in vitro experiments were conducted that revealed A549 cell treatment with lysosome-targeting Ru3-M triggered oxidative stress, induced mitochondrial membrane potential depolarization, and drastically reduced intracellular ATP levels. Taken together, these results demonstrated that Ru3-M killed cells mainly via a non-apoptotic pathway known as oncosis, as evidenced by observed Ru3-M-induced cellular morphological changes including cytosolic flushing, cell swelling, and cytoplasmic vacuolation. In turn, these changes together caused cytoskeletal collapse and activation of porimin and calpain1 proteins with known oncotic functions that distinguished this oncotic process from other cell death processes. In summary, Ru3-M is a potential anticancer agent that kills A549 cells via a novel mechanism involving Ru(II) complex triggering of cell death via oncosis.

Antimicrobial potential of a biosurfactant gel for the prevention of mixed biofilms formed by fluconazole-resistant C. albicans and methicillin-resistant S. aureus in catheters.

Dual-species biofilms formed by Candida albicans and Staphylococcus aureus have high virulence and drug resistance. In this context, biosurfactants produced by Pseudomonas aeruginosa have been widely studied, of which a new derivative (RLmix_Arg) stands out for possible application in formulations. The objective of this study was to evaluate the antibiofilm activity of RLmix_Arg, both alone and incorporated in a gel prepared with Pluronic F-127, against dual-species biofilms of fluconazole-resistant C. albicans (FRCA) and methicillin-resistant S. aureus (MRSA) in impregnated catheters. Broth microdilution tests, MTT reduction assays of mature biofilms, impregnation of RLmix_Arg and its gel in peripheral venous catheters, durability tests and scanning electron microscopy (SEM) were performed. RLmix_Arg showed antimicrobial activity against Candida spp. and S. aureus, by reducing the cell viability of mixed biofilms of FRCA and MRSA, and preventing their formation in a peripheral venous catheter. The incorporation of this biosurfactant in the Pluronic F-127 gel considerably enhanced its antibiofilm activity. Thus, RLmix_Arg has potential application in gels for impregnation in peripheral venous catheters, helping to prevent development of dual-species biofilms of FRCA and MRSA.

Treatment using vanillin-derived synthetic molecules incorporated into polymeric micelles is effective against infection caused by Leishmania amazonensis species.

Treatment against leishmaniasis presents problems, mainly due to the toxicity of the drugs, high cost, and the emergence of resistant strains. A previous study showed that two vanillin-derived synthetic molecules, 3s [4-(2-hydroxy-3-(4-octyl-1H-1,2,3-triazol-1-yl)propoxy)-3-methoxybenzaldehyde] and 3t [4-(3-(4-decyl-1H-1,2,3-triazol-1-yl)-2-hydroxypropoxy)-3-methoxybenzaldehyde], presented antileishmanial activity against Leishmania infantum, L. amazonensis, and L. braziliensis species. In the present work, 3s and 3t were evaluated to treat L. amazonensis-infected mice. Molecules were used pure or incorporated into Poloxamer 407-based micelles. In addition, amphotericin B (AmpB) and its liposomal formulation, Ambisome®, were used as control. Animals received the treatment and, one and 30 days after, they were euthanized to evaluate immunological, parasitological, and biochemical parameters. Results showed that the micellar compositions (3s/Mic and 3t/Mic) induced significant reductions in the lesion mean diameter and parasite load in the infected tissue and distinct organs, as well as a specific and significant antileishmanial Th1-type immune response, which was based on significantly higher levels of IFN-γ, IL-12, nitrite, and IgG2a isotype antibodies. Drug controls showed also antileishmanial action; although 3s/Mic and 3t/Mic have presented better and more significant parasitological and immunological data, which were based on significantly higher IFN-γ production and lower parasite burden in treated animals. In addition, significantly lower levels of urea, creatinine, alanine transaminase, and aspartate transaminase were found in mice treated with 3s/Mic and 3t/Mic, when compared to the others. In conclusion, results suggest that 3s/Mic and 3t/Mic could be considered as therapeutic candidates to treat against L. amazonensis infection.

Pluronic F127 hydrogel-loaded extracellular vesicles from adipose-derived mesenchymal stem cells promote tracheal cartilage regeneration via SCNN1B delivery.

Extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (AMSC-EVs) have been highlighted as a cell-free therapy due to their regenerative capability to enhance tissue and organ regeneration. Herein, we aimed to examine the mechanism of PF127-hydrogel@AMSC-EVs in promoting tracheal cartilage defect repair. Based on bioinformatics methods, SCNN1B was identified as a key gene for the osteogenic differentiation of AMSCs induced by AMSC-EVs. EVs were isolated from rat AMSCs and then loaded onto thermo-sensitive PF-127 hydrogel to develop PF127-hydrogel@AMSC-EVs. It was established that PF127-hydrogel@AMSC-EVs could effectively deliver SCNN1B into AMSCs, where SCNN1B promoted AMSC osteogenic differentiation. The promotive effect was evidenced by enhanced ALP activity, extracellular matrix mineralization, and expression of s-glycosaminoglycan, RUNX2, OCN, collagen II, PERK, and ATF4. Furthermore, the in vivo experiments revealed that PF127-hydrogel@AMSC-SCNN1B-EVs stimulated tracheal cartilage regeneration in rats through PERK/ATF4 signaling axis activation. Therefore, PF127-hydrogel@AMSC-SCNN1B-EVs may be a novel cell-free biomaterial to facilitate tracheal cartilage regeneration and cartilage injury repair.

Pea Seed Priming with Pluronic P85-Grafted Single-Walled Carbon Nanotubes Affects Photosynthetic Gas Exchange but Not Photosynthetic Light Reactions.

Nanotechnology is rapidly advancing towards the development of applications for sustainable plant growth and photosynthesis optimization. The nanomaterial/plant interaction has been intensively investigated; however, there is still a gap in knowledge regarding their effect on crop seed development and photosynthetic performance. In the present work, we apply a priming procedure with 10 and 50 mg/L Pluronic-P85-grafted single-walled carbon nanotubes (P85-SWCNT) on garden pea seeds and examine the germination, development, and photosynthetic activity of young seedlings grown on soil substrate. The applied treatments result in a distorted topology of the seed surface and suppressed (by 10-19%) shoot emergence. No priming-induced alterations in the structural and functional features of the photosynthetic apparatus in 14-day-old plants are found. However, photosynthetic gas exchange measurements reveal reduced stomatal conductance (by up to 15%) and increased intrinsic water use efficiency (by 12-15%), as compared to hydro-primed variants, suggesting the better ability of plants to cope with drought stress-an assumption that needs further verification. Our study prompts further research on the stomatal behavior and dark reactions of photosynthesis in order to gain new insights into the effect of carbon nanotubes on plant performance.

Effects of Commonly used Surfactants, Poloxamer 188 and Tween 80, on the Drug Transport Capacity of Intestinal Glucose Transporters.

Some glycoside drugs can be transported through intestinal glucose transporters (IGTs). The surfactants used in oral drug preparations can affect the function of transporter proteins. This study aimed to investigate the effect of commonly used surfactants, Poloxamer 188 and Tween 80, on the drug transport capacity of IGTs. Previous studies have shown that gastrodin is the optimal drug substrate for IGTs. Gastrodin was used as a probe drug to evaluate the effect of these two surfactants on intestinal absorption in SD rats through pharmacokinetic and in situ single-pass intestinal perfusion. Then, the effects of the two surfactants on the expression of glucose transporters and tight-junction proteins were examined using RT-PCR and western blotting. Additionally, the effect of surfactants on intestinal permeability was evaluated through hematoxylin-eosin staining. The results found that all experimental for Poloxamer 188 (0.5%, 2.0% and 8.0%) and Tween 80 (0.1% and 2.0%) were not significantly different from those of the blank group. However, the AUC(0-∞) of gastrodin increased by approximately 32% when 0.5% Tween 80 was used. The changes in IGT expression correlated with the intestinal absorption of gastrodin. A significant increase in the expression of IGTs was observed at 0.5% Tween 80. In conclusion, Poloxamer 188 had minimal effect on the drug transport capacity of IGTs within the recommended limits of use. However, the expression of IGTs increased in response to 0.5% Tween 80, which significantly enhanced the drug transport capacity of IGTs. However, 0.1% and 2.0% Tween 80 had no significant effect.

Gabexate Mesylate-Poloxamer 407 Conjugate Alleviates Sodium Taurocholate-Induced Severe Acute Pancreatitis in an Optimized Rat Model.

BACKGROUND AND AIMS: We have previously shown that gabexate mesylate-poloxamer 407 conjugate (GMTI) alleviates traumatic pancreatitis in rats. In this study, we evaluated the therapeutic effect of GMTI on sodium taurocholate-induced severe acute pancreatitis (SAP) in an optimized rat model. METHODS: An SAP rat model was established via microinjection of 3.5% sodium taurocholate and retention in the bile duct for 1 min. SAP rats were administered GMTI via tail vein injection (i.v.) or tail vein injection + intraperitoneal injection (i.v. + i.p.). All rats were sacrificed at 12 h after treatment. Biochemical approach and enzyme-linked immunosorbent assay were performed to measure the serum levels of amylase (AMY), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Hematoxylin and eosin staining and TUNEL assay were conducted to examine histopathology and acinar cell apoptosis in the rat pancreas. RESULTS: SAP was successfully induced in all model rats, as evidenced by progressively aggravating SAP symptoms and signs, pancreatic histopathological abnormalities, as well as elevated serum levels of TNF-α, IL-6, and AMY. The mortality rates at 1 h, 6 h, and 12 h were 0%, 0%, and 25%, respectively. GMTI therapy via i.v. or i.v. + i.p. significantly reduced pancreatic wet weights, ascites amounts, pathological scores, and circulating levels of TNF-α and IL-6 while promoting acinar cell apoptosis in SAP rats. GMTI therapy via i.v. + i.p. outperformed i.v. in improving pancreatic histology and reducing TNF-α and IL-6 serum levels in SAP rats. CONCLUSIONS: Our optimized SAP rat model is reliable and reproducible. GMTI therapy is a promising approach against SAP.

P188 Therapy in In Vitro Models of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality worldwide. Varied mechanisms of injury contribute to the heterogeneity of this patient population as demonstrated by the multiple published grading scales and diverse required criteria leading to diagnoses from mild to severe. TBI pathophysiology is classically separated into a primary injury that is characterized by local tissue destruction as a result of the initial blow, followed by a secondary phase of injury constituted by a score of incompletely understood cellular processes including reperfusion injury, disruption to the blood-brain barrier, excitotoxicity, and metabolic dysregulation. There are currently no effective pharmacological treatments in the wide-spread use for TBI, in large part due to challenges associated with the development of clinically representative in vitro and in vivo models. Poloxamer 188 (P188), a Food and Drug Administration-approved amphiphilic triblock copolymer embeds itself into the plasma membrane of damaged cells. P188 has been shown to have neuroprotective properties on various cell types. The objective of this review is to provide a summary of the current literature on in vitro models of TBI treated with P188.

Evaluation of Antibacterial Efficacy of Two Commercially Available Probiotics as Intracanal Medicament against Enterococcus faecalis: An In Vitro Study.

AIM: This study was performed to evaluate the antibacterial efficacy of two commercially available probiotics (BIFILAC and VSL 3) as intracanal medicament against Enterococcus faecalis in endodontic therapy. MATERIALS AND METHODS: Microorganisms from commercially available probiotics (BIFILAC and VSL 3) were extracted via the manufacturer's recommendations and mixed by weight. About 30 microliters were then placed on sterile discs. The pathogenic test organism was E. faecalis set to a 1 McFarland standard challenge. A two-probiotic disc template on blood agar plates was inoculated with E. faecalis and incubated at 37°C for 48 hours and 1 week respectively. Phase-1 of the study was conducted by a disc diffusion assay test to evaluate zones of inhibition (ZOI) in millimeters (mm). Phase-2 was conducted by mixing 9 mL of 30% poloxamer 407 and MRS broth in a test tube, together with the two probiotic mixtures and E. faecalis, set at a 2 McFarland standard. Serial dilutions up to 108 were done and the mixture was placed inside root canals and incubated at 37ºC for 36 hours and evaluated for colony-forming unit (CFU)/mL counts. RESULTS: The results of phase-1 showed that probiotics Lactobacillus rhamnosus and Bifidobacterium species are effective in fighting against E. faecalis with the acceptable zone of inhibition. The results of phase-2 showed that both the probiotics are effective against E. faecalis with a reduction in the number of CFU after probiotic usage. CONCLUSION: Commercially available probiotics can be used effectively as an intracanal medicament to fight against E. faecalis, Poloxamer 407 is a promising vehicle for delivering probiotics inside the root canal system. Further in vitro and in vivo studies are needed to determine the full potential of "Bacteriotherapy" with an application of probiotics. CLINICAL SIGNIFICANCE: If probiotics are proved to be an effective intracanal medicament against E.faecalis they can be used as an alternative to calcium hydroxide as intracanal medicament with no side effects to the host.

All-in-one nanosponge with pluronic shell for synergistic anticancer therapy through effectively overcoming multidrug resistance in cancer.

Overexpression of P-glycoprotein (P-gp) on cancer cells is a major hurdle to effectively treat tumors with multidrug resistance (MDR). The current study aimed to explore anticancer drug and P-gp inhibitor delivery as a promising strategy to efficiently treat colorectal cancer with MDR. To this end, a multidrug-loaded all-in-one nanosponge (ANS) was developed to simultaneously deliver doxorubicin (DOX), paclitaxel (PTX), and the P-gp inhibitor tetrandrine (TET), referred to as DOX/PTX/TET@ANS, without chemical conjugation. ANS with high loading content and efficiency facilitated a pH-dependent and controlled release with different profiles. Compared to free drugs and DOX/PTX@ANS, DOX/PTX/TET@ANS exhibited more effective anticancer effects on P-gp-overexpressing colorectal cancer cells and solid tumor mouse xenografts, without major toxicity. Notably, ANS composed of pluronic shell induced in vitro P-gp inhibition compared to TET, implying a synergistic anticancer effect. These findings suggest that ANS can encapsulate multiple drugs to efficiently deliver chemotherapy, particularly in MDR tumors.

Effect of curcumin-encapsulated Pluronic® F-127 over duo-species biofilm of Streptococcus mutans and Candida albicans.

To assess the effect of curcumin-encapsulated Pluronic® F-127 (Cur-Plu) during antimicrobial photodynamic therapy (aPDT) over duo-species biofilm of Streptococcus mutans and Candida albicans. Thermal analysis, optical absorption, and fluorescence spectroscopy were evaluated. Minimum inhibitory concentration (MIC) and minimum bactericidal/fungal concentration were obtained. The biofilms were cultured for 48 h at 37 °C and treated according to the groups: P + M + L + (photosensitizer encapsulated with Pluronic® F-127 + light); P + D + L + (photosensitizer incorporated in 1% DMSO + light); P - M + L + (no Pluronic® F-127 + light); P - D + L + (1% DMSO + light); P - L + (Milli-Q water + light); P + M + L - (photosensitizer encapsulated with Pluronic® F-127 no light); P + D + L - (photosensitizer in 1% DMSO, no light); P - M + L - (Pluronic® F-127 no light); P - D + L - (1% DMSO, no light); P - L - (Milli-Q water, no light; negative control group); CHX (0.2% chlorhexidine, positive control group); and NYS (Nystatin). Dark incubation of 5 min was used. The groups that received aPDT were irradiated by blue LED (460 nm, 15 J/cm2). Cell viability of the biofilms was performed by colony-forming units (CFU/mL) and confocal microscopy. Two-way ANOVA followed by Tukey's post hoc test was used at a significance level of 5%. P + D + L + and P + M + L + groups exhibited better log-reduction for both Candida albicans and Streptococcus mutans biofilms than P - M + L + , P - L + , and P - D + L + experimental groups. Furthermore, P + M + L + and P + D + L + showed greater reduction for Candida albicans than for Streptococcus mutans. aPDT mediated by Cur-Plu can be a potential strategy for biofilm control against duo-species biofilm of Streptococcus mutans and Candida albicans.

Connexin Signaling Is Involved in the Reactivation of a Latent Stem Cell Niche after Spinal Cord Injury.

The ependyma of the adult spinal cord is a latent stem cell niche that is reactivated by spinal cord injury contributing new cells to the glial scar. The cellular events taking place in the early stages of the reaction of the ependyma to injury remain little understood. Ependymal cells are functionally heterogeneous with a mitotically active subpopulation lining the lateral domains of the central canal (CC) that are coupled via gap junctions. Gap junctions and connexin hemichannels are key regulators of the biology of neural progenitors during development and in adult neurogenic niches. Thus, we hypothesized that communication via connexins in the CC is developmentally regulated and may play a part in the reactivation of this latent stem cell niche after injury. To test these possibilities, we combined patch-clamp recordings of ependymal cells with immunohistochemistry for various connexins in the neonatal and the adult (P > 90) normal and injured spinal cord of male and female mice. We find that coupling among ependymal cells is downregulated as postnatal development proceeds but increases after injury, resembling the immature CC. The increase in gap junction coupling in the adult CC was paralleled by upregulation of connexin 26, which correlated with the resumption of proliferation and a reduction of connexin hemichannel activity. Connexin blockade reduced the injury-induced proliferation of ependymal cells. Our findings suggest that connexins are involved in the early reaction of ependymal cells to injury, representing a potential target to improve the contribution of the CC stem cell niche to repair.SIGNIFICANCE STATEMENT Ependymal cells in the adult spinal cord are latent progenitors that react to injury to support some degree of endogenous repair. Understanding the mechanisms by which these progenitor-like cells are regulated in the aftermath of spinal cord injury is critical to design future manipulations aimed at improving healing and functional recovery. Gap junctions and connexin hemichannels are key regulators of the biology of neural progenitors during development and in adult neurogenic niches. We find here that connexin signaling in the ependyma changes after injury of the adult spinal cord, functionally resembling the immature active-stem cell niche of neonatal animals. Our findings suggest that connexins in ependymal cells are potential targets to improve self-repair of the spinal cord.

Electrophysiological analysis of healthy and dystrophic 3-D bioengineered skeletal muscle tissues.

Recently, methods for creating three-dimensional (3-D) human skeletal muscle tissues from myogenic cell lines have been reported. Bioengineered muscle tissues are contractile and respond to electrical and chemical stimulation. In this study, we provide an electrophysiological analysis of healthy and dystrophic 3-D bioengineered skeletal muscle tissues, focusing on Duchenne muscular dystrophy (DMD). We enlist the 3-D in vitro model of DMD muscle tissue to evaluate muscle cell electrical properties uncoupled from presynaptic neural inputs, an understudied aspect of DMD. Our data show that previously reported electrophysiological aspects of DMD, including effects on membrane potential and membrane resistance, are replicated in the 3-D muscle tissue model. Furthermore, we test a potential therapeutic compound, poloxamer 188, and demonstrate capacity for improving the membrane potential in DMD muscle. Therefore, this study serves as a baseline for a new in vitro method to examine potential therapies for muscular disorders.

Skin microbiota dynamics following B. subtilis formulation challenge: an in vivo study in mice.

BACKGROUND: Modulating the microbiota is a leading-edge strategy for the restoration and maintenance of a healthy, balanced environment. The use of health-promoting bacteria has demonstrated some potential benefits as an alternative for skin microbiota intervention. Here, we investigate the manipulation of mice skin microbiota using B. subtilis incorporated into a supportive Pluronic F-127 hydrogel formulation. The formula plays an important role in delivering the bacteria to the desired action site. RESULTS: The B. subtilis challenge induced a shift in the composition and abundance of the skin microbiota. Containment of B. subtilis in the Pluronic F-127 hydrogel accelerated bacterial modulation compared with free B. subtilis. The abundance of both Staphylococcus and Corynebacterium spp. was altered as a result of the live bacterial intervention: the abundance of Corynebacterium increased while that of Staphylococcus decreased. Four days after last application of the B. subtilis formulation, B. subtilis counts returned to its initial level. CONCLUSIONS: B. subtilis intervention can induce a shift in the skin microbiota, influencing the abundance of commensal, beneficial, and pathogenic bacteria. Containment of B. subtilis in Pluronic hydrogel accelerates the microbial alteration, probably by facilitating bacterial attachment and supporting continuous growth. Our results reveal the ability of B. subtilis in Pluronic to modulate the skin microbiota composition, suggesting that the formulation holds therapeutic potential for skin disease treatment.

Codelivery of satraplatin and aminopyrrolic receptor with Pluronic F127-based polyaniline nanoparticles with NIR induced release for combined chemotherapy.

The acquired drug resistance of the platinum-based drug is a main obstacle in cancer therapy. Herein, an aminopyrrolic receptor 1 was synthesized to sensitize satraplatin for overcoming the drug resistance as well as improving tumor targeted ability. Thus, Pluronic F127-based polyaniline nanoparticles were designed to co-deliver satraplatin and aminopyrrolic receptor 1, which could control the drug release with the Near Infrared laser irradiation (808 nm) due to the polyaniline mediated photothermal conversion. Biological evaluation shows prepared nanoparticles (Pt-ARNPs) exhibited more effective cytotoxicity (IC50 = 2.7µM) against the tested cancer cell lines under laser irradiation, compared with free satraplatin or treatment without Near-infrared radiation. Moreover, Pt-ARNPs showed comparable cytotoxicity against A549 and A549/cis cells, implying that the combination of satraplatin and aminopyrrolic receptor 1 with nano carrier might be a promising strategy to reduce platinum resistance and improve therapeutic effect in cancer therapy.

No Direct Postconditioning Effect of Poloxamer 188 on Mitochondrial Function after Ischemia Reperfusion Injury in Rat Isolated Hearts.

Myocardial infarction is a leading cause for morbidity and mortality worldwide. The only viable treatment for the ischemic insult is timely reperfusion, which further exacerbates myocardial injury. Maintaining mitochondrial function is crucial in preserving cardiomyocyte function in ischemia reperfusion (IR) injury. Poloxamer (P) 188 has been shown to improve cardiac IR injury by improving cellular and mitochondrial function. The aim of this study was to show if P188 postconditioning has direct protective effects on mitochondrial function in the heart. Langendorff prepared rat hearts were subjected to IR injury ex-vivo and reperfused for 10 min with 1 mM P188 vs. vehicle. Cardiac mitochondria were isolated with 1 mM P188 vs. 1 mM polyethylene glycol (PEG) vs. vehicle by differential centrifugation. Mitochondrial function was assessed by adenosine triphosphate synthesis, oxygen consumption, and calcium retention capacity. Mitochondrial function decreased significantly after ischemia and showed mild improvement with reperfusion. P188 did not improve mitochondrial function in the ex-vivo heart, and neither further P188 nor PEG induced direct mitochondrial protection after IR injury in this model.

Polymeric Drug Delivery System Based on Pluronics for Cancer Treatment.

Pluronic polymers (pluronics) are a unique class of synthetic triblock copolymers containing hydrophobic polypropylene oxide (PPO) and hydrophilic polyethylene oxide (PEO) arranged in the PEO-PPO-PEO manner. Due to their excellent biocompatibility and amphiphilic properties, pluronics are an ideal and promising biological material, which is widely used in drug delivery, disease diagnosis, and treatment, among other applications. Through self-assembly or in combination with other materials, pluronics can form nano carriers with different morphologies, representing a kind of multifunctional pharmaceutical excipients. In recent years, the utilization of pluronic-based multi-functional drug carriers in tumor treatment has become widespread, and various responsive drug carriers are designed according to the characteristics of the tumor microenvironment, resulting in major progress in tumor therapy. This review introduces the specific role of pluronic-based polymer drug delivery systems in tumor therapy, focusing on their physical and chemical properties as well as the design aspects of pluronic polymers. Finally, using newer literature reports, this review provides insights into the future potential and challenges posed by different pluronic-based polymer drug delivery systems in tumor therapy.