Pluronic Research Articles

Quantification of Pluronic F127 used on PLGA nanoparticle preparation and comparing purification techniques by centrifugation, tangential flow filtration, and ultrafiltration

Emerging research in polymeric nanoparticles (PNP) in the field of drug delivery systems focuses on the preferable use of biocompatible materials like poly(lactic-co-glycolic) acid (PLGA). However, the substantial use of surfactant in achieving colloidal stability requires its subsequent elimination to avoid side effects. This study aimed to establish suitable conditions for detecting and quantifying Pluronic® F127 (F127), a non-ionic surfactant widely used for this specific purpose, through a precise Size Exclusion Chromatography (SEC) method. Then, comparing the F127 removal efficacy via three purification techniques: Centrifugation (Cf), Ultrafiltration (UF), and tangential flow filtration (TFF), determining the minor influence of surfactant removal on the colloidal and morphological properties of surfactant-free PLGA suspensions. Thus, to determine the most suitable strategy for purifying PNP. The initial results of the SEC method revealed two distinct molar mass distributions of F127, associated with a blend of triblock alongside a minor fraction of homopolymer or diblock. The method exhibited a high linear correlation (R2 0.99991) for surfactant concentrations ranging from 0.3 to 14.7 mg/mL. While assessing the three purification techniques, UF demonstrated proficiency in concentrating nanoparticle suspensions, albeit tending to retain a significant portion of the surfactant. In contrast, Cf displayed a remarkable capability in removing more than 90 % of the incorporated F127. However, Cf recovered only 60 % of the initial nanoparticles, predominantly eliminating smaller diameter particles. Conversely, TFF demonstrated high efficacy in surfactant removal, requiring an extended washing process and leading to minimal nanoparticle loss while leaving the colloidal variables unaffected.

A facile one-step self-assembly strategy for constructing biocompatible and pH-sensitive polyphenol-based nanoparticles for high-efficiency tumor therapy

Self-assembled supramolecular nanoparticles possess several advantages, including convenient preparation process, high controllability, stability, and multifunctionality, which make them highly beneficial as drug-carriers in field of drug delivery. Size of nano-carriers plays a crucial role in their performance, affecting their ability for long-term circulation and deep penetration into tumor tissues within biological systems. In this study, we present a simple one-step self-assembly strategy for constructing biocompatible and pH-sensitive polyphenol-based nanoparticles for high-efficiency tumor therapy. The self-assembled DOX@F127-TA nanoparticles are achieved through a combination of hydrogen bonding and hydrophobic interactions. The Pluronic F127 (F127) and tannic acid (TA) endow high biocompatibility and satisfactory safety to nano-drug carriers. By adjusting DOX content, DOX@F127-TA nanoparticles are successfully prepared with advantages of high drug content, pH-sensitive, high stability and small size. Additionally, the nanoparticles exhibit low hemolysis performance and electronegativity, which contribute to their long-term circulation stability in vivo. Furthermore, in vitro cytotoxicity, cellular uptake and patient-derived organoids were utilized to evaluate the efficacy of the DOX@F127-TA. The results demonstrate efficient endocytosis, successful organoid drug delivery, and remarkable anti-tumor effects, while exhibiting minimal toxicity to normal cells. Overall, DOX@F127-TA nanoparticles demonstrate great potential as a promising drug delivery platform for high-efficient cancer therapy and practical application.

Design of polymeric carriers to enhance antimicrobial photodynamic inactivation

Mixed polymeric micelles are a promising tool for the design of nanocarriers with pharmaceutical properties. These micellar systems allow reversing numerous properties of lipophilic drugs. Particularly, when applied to transport photosensitizers (PSs), they give rise to a wide variety of nanophotosensitizers (nPSs). These compounds are used to inactivate numerous bacteria resistant to conventional antibiotics. This research proposes the development of new mixed micelles, with better properties than simple micelles, for the trapping of Neutral Red (NR) and its monobrominated derivative (NRBr). Based on the combination of Pluronic P-123 with Pluronic F-108, Pluronic L-61 and Tween 80, 15 binary micellar systems were obtained. These mixed micelles presented a single population of homogeneous particles, with a diameter less than 70 nm. Moreover, several mixed micelles show smaller CMC than the simple system. These properties are predictors of high micellar stability and good anti-dilution properties, favoring their drug delivery applications. For these reasons, were loaded with NR and NRBr, showing good encapsulation efficiency. The 30 new nPSs presented an adequate size for pharmaceutical use and markedly enhanced the photochemical reactivity of the free PSs. Many of the mixed micellar systems showed greater production of singlet oxygen than the simple micelles of Pluronic P-123. Furthermore, all micellar systems increased the chemical stability of NRBr, which degrades in pH 7.4 buffer solution. Finally, all nPSs presented greater phototoxic activity against methicillin-resistant Staphylococcus aureus than free PSs. The nPSs formed by P-123: F-108 (90:10) + NR, P-123: F-108 (90:10) + NRBr, P-123: L-61 (80:20) + NRBr and P −123: T80 (80:20) + NRBr caused greater photodynamic inactivation of the microorganism than simple P-123 micellar systems. These nPSs could be considered excellent candidates for application in the treatment of infections caused by bacteria resistant to antibiotics.

Thermally-responsive and reduced glutathione-sensitive folate-targeted nanocarrier based on alginate and pluronic F127 for on-demand release of methotrexate

A specific rheumatoid arthritis (RA)-microenvironment-triggered nanocarrier for RA treatment of a first-line antirheumatic drug (Methotrexate, MTX) has been proposed. Reduced glutathione (GSH) responsivity, cystamine, was first introduced on the alginate backbone, which was then used as the bridge to connect pluronic F127 (temperature-responsive factor) and folic acid (targeting factor for active immune cells), resulting in dual-responsive triggered targeting carrier, PCAC-FA. In vitro study demonstrated that PCAC-FA was preferentially taken up by activated macrophage cells rather than normal ones, suggesting the targeting of PCAC-FA to inflamed tissue. The loading capacity of the designed carrier was 21.23 ± 0.91 %. MTX from the PCAC-FA carrier was significantly accelerated release in the presentation of glutathione or in cold shock condition, proposing the efficacy-controlled release. MTX@PCAC-FA showed excellent hemocompatibility, confirming a suitable application with parenteral administration. Notably, the acute and subacute toxicity in the mice model showed that the toxicity of MTX had significantly reduced after encapsulating in the PCAC-FA carrier. These nanoplatforms not only provide an alternative safe strategy for the clinical treatment of rheumatoid arthritis with MTX but also deliver MTX selectively and provide on-demand drug release via external and internal signals, thus emerging as a promising therapeutic option for precise RA therapy.

Excimer emission from polycyclic arenes bearing triphenylmethyl group: Solid-state fluorescence, mechanofluorochromism, aggregation-induced emission and cell imaging application

The excimer emission based on discrete π-stacked dimers of polycyclic π-systems has generated significant interest in the structure-luminescence relationship of excimers owing to their ultra-large Stokes shift. Herein, a series of excimer emissive luminogens were obtained by conjugating different polycyclic aromatic aldehydes (anthraldehyde, pyrenealdehyde and perylenealdehyde) with triphenylmethylamine. In crystalline states, all the molecules were arranged in the form of π-stacked arene dimers which were spatially isolated from each other by the bulky triphenylmethyl groups, and thus emitted bright excimer emission. The anthracene and pyrene derivatives showed fluorescence enhancement responses to grinding and the enhanced fluorescence could recover to the original state upon heating. The aggregation-induced emission (AIE) properties of them were dependent on the shapes and sizes of the polycyclic aromatic groups. The pyrene derivative showed the most excellent excimer-based AIE behavior among them. All of them were more apt to exhibit the excimer emission when formed nanoparticles with pluronic F-127 than that without pluronic F-127. Furthermore, PETP was utilized for bioimaging of living Hela cells and the high-resolution image was observed.

Modulation of Heterotypic and Homotypic Interactions to Visualize the Evolution of Organic Aggregates in a Fluorescence Turn-on Manner.

The abnormal evolution of membrane-less organelles into amyloid fibrils is a causative factor in many neurodegenerative diseases. Fundamental research on evolving organic aggregates is thus instructive for understanding the root causes of these diseases. In-situ monitoring of evolving molecular aggregates with built-in fluorescence properties is a reliable approach to reflect their subtle structural variation. To increase the sensitivity of real-time monitoring, we presented organic aggregates assembled by TPAN-2MeO, which is a triphenyl acrylonitrile derivative. TPAN-2MeO showed a morphological evolution with distinct turn-on emission. Upon rapid nanoaggregation, it formed non-emissive spherical aggregates in the kinetically metastable state. Experimental and simulation results revealed that the weak homotypic interactions between the TPAN-2MeO molecules liberated their molecular motion for efficient non-radiative decay, and the strong heterotypic interactions between TPAN-2MeO and water stabilized the molecular geometry favorable for the non-fluorescent state. After ultrasonication, the decreased heterotypic interactions and increased homotypic interactions acted synergistically to allow access to the emissive thermodynamic equilibrium state with a decent photoluminescence quantum yield (PLQY). The spherical aggregates were eventually transformed into micrometer-sized blocklike particles. Under mechanical stirring, the co-assembly of TPAN-2MeO and Pluronic F-127 formed uniform fluorescent platelets, inducing a significant enhancement in PLQY. These results decipher the stimuli-triggered structural variation of organic aggregates with concurrent sensitive fluorescence response and pave the way for a deep understanding of the evolutionary events of biogenic aggregates.

Tailoring pore size of mesoporous silica and organosilica using biodegradable pentablock copolymer templates via EISA process

In this work, we have designed unique poly(lactic acid-co-glycolic acid)-b-poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide)-b-poly(lactic acid-co-glycolic acid) pentablock copolymers using Pluronic F68 and F108 triblock copolymers as macroinitiators. The poly(lactic acid-co-glycolic acid) (PLGA) blocks were attached as glycolide and lactide monomers at the both ends of each F68 and F108 triblock copolymer. The molecular weights and the block fractions were confirmed by gel permeation chromatography (GPC) and proton nuclear magnetic resonance (1H NMR) for the four kinds of pentablock copolymers. Using these pentablock copolymers as templates, we synthesized mesoporous ethane-silicas as well as silicas by the evaporation-induced self-assembly (EISA) method. 1,2-bis(triethoxysily)ethane (BTEE) were used as an organosilica precursor. The mesoporous ethane-silica samples were characterized using synchrotron small angle X-ray scattering (SAXS), nitrogen sorption experiments, transmission electron microscopy (TEM), and solid-state 29Si CP-MAS NMR. Based on the experimental results, it was confirmed that the porosity and pore diameter can be varied with the PLGA weight fraction of the pentablock copolymer. It is due to the PLGA block in polymer forming the hydrophobic domain in micelles, which leads to the formation of increased pore size over 20 nm without any additive pore expander. In addition, it seems that as the organosilica precursor increases, the association number of block copolymers forming one micelle decreases, resulting in a decrease in pore size. In summary, the polymer template plays a vital part in tuning the structure of the mesoporous ethane-silica samples. Thus, the development of synthetic method of mesoporous organosilica materials using polymer templates with different topology is still challenging and can endow the unique structure and property for mesoporous organosilica for future applications.

An Activatable Dual Polymer Nanosystem for Photoimmunotherapy and Metabolic Modulation of Deep-Seated Tumors.

Nanomedicine in combination with immunotherapy has shown great potential in the cancer treatment, but phototherapeutic nanomaterials that specifically activate the immunopharmacological effects in deep tumors have rarely been developed due to limited laser penetration depth and tumor immune microenvironment. Herein, this work reports a newly synthesized semiconducting polymer (SP) grafted with imiquimod R837 and indoxmid encapsulated micelle (SPRIN-micelle) with strong absorption in the second near infrared window (NIR-II) that can relieve tumor immunosuppression and enhance the photothermal immunotherapy and catabolic modulation on tumors. Immune agonists (Imiquimod R837) and immunometabolic modulators (indoxmid) are covalently attached to NIR-II SP sensors via a glutathione (GSH) responsive self-immolation linker and then loaded into Pluronic F127 (F127) micelles by a temperature-sensitive critical micelle concentration (CMC)-switching method. Using this method, photothermal effect of SPRIN-micelles in deep-seated tumors can be activated, leading to effective tumor ablation and immunogenic cell death (ICD). Meanwhile, imiquimod and indoxmid are tracelessly released in response to the tumor microenvironment, resulting in dendritic cell (DC) maturation by imiquimod R837 and inhibition of both indoleamine 2,3-dioxygenase (IDO) activity and Treg cell expression by indoxmid. Ultimately, cytotoxic T-lymphocyte infiltration and tumor metastasis inhibition in deep solid tumors (9mm) are achieved. In summary, this work demonstrates a new strategy for the combination of photothermal immunotherapy and metabolic modulation by developing a dual functional polymer system including activable SP and temperature-sensitive F127 for the treatment of deep solid tumors.

Design of Liquid Formulation Based on F127-Loaded Natural Dimeric Flavonoids as a New Perspective Treatment for Leishmaniasis.

Infectious and Parasitic Diseases (IPD) remain a challenge for medicine due to several interconnected reasons, such as antimicrobial resistance (AMR). American tegumentary leishmaniasis (ATL) is an overlooked IPD causing persistent skin ulcers that are challenging to heal, resulting in disfiguring scars. Moreover, it has the potential to extend from the skin to the mucous membranes of the nose, mouth, and throat in both humans and various animals. Given the limited effectiveness and AMR of current drugs, the exploration of new substances has emerged as a promising alternative for ATL treatment. Arrabidaea brachypoda (DC). Bureau is a native Brazilian plant rich in dimeric flavonoids, including Brachydin (BRA), which displays antimicrobial activity, but still little has been explored regarding the development of therapeutic formulations. In this work, we present the design of a low-cost liquid formulation based on the use of Pluronic F127 for encapsulation of high BRA concentration (LF-B500). The characterization techniques revealed that BRA-loaded F127 micelles are well-stabilized in an unusual worm-like form. The in vitro cytotoxicity assay demonstrated that LF-B500 was non-toxic to macrophages but efficient in the inactivation of forms of Leishmania amazonensis promastigotes with IC50 of 16.06 µg/mL. The results demonstrated that LF-B500 opened a new perspective on the use of liquid formulation-based natural products for ATL treatment.

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.

Long-acting anti-inflammatory injectable DEX-Gel with sustained release and self-healing properties regulates TH1/TH2 immune balance for minimally invasive treatment of allergic rhinitis

BackgroundAllergic rhinitis (AR) is a prevalent immune-related allergic disease, and corticosteroid nasal sprays serve as the primary treatment for this patient population. However, their short duration of efficacy and frequent administration pose challenges, leading to drug wastage and potential adverse effects. To overcome these limitations, we devised a novel approach to formulate DEX-Gel by incorporating dexamethasone (DEX) into a blend of Pluronic F127, stearic acid (SA), and polyethylene glycol 400 (PEG400) to achieve sustained-release treatment for AR.ResultsFollowing endoscopic injection into the nasal mucosa of AR rats, DEX-Gel exhibited sustained release over a 14-day period. In vivo trials employing various assays, such as flow cytometry (FC), demonstrated that DEX-Gel not only effectively managed allergic symptoms but also significantly downregulated helper T-cells (TH) 2 and TH2-type inflammatory cytokines (e.g., interleukins 4, 5, and 13). Additionally, the TH1/TH2 cell ratio was increased.ConclusionThis innovative long-acting anti-inflammatory sustained-release therapy addresses the TH1/TH2 immune imbalance, offering a promising and valuable approach for the treatment of AR and other inflammatory nasal diseases.Graphical

Formulation, characterization, in vitro and in vivo evaluation of thermoresponsive lawsone-based Pluronic F-127 nanogels for wound healing

The aim of the present study was to formulate and characterize lawsone-loaded Pluronic F-127 based nanogels for wound healing application. Polymeric nanoparticles at different concentrations (0.5 %, 1 %, 1.5 %) were prepared employing Eudragit RS100 via solvent evaporation technique followed by incorporation of Pluronic F-127 into the respective batches of nanoparticles to formulate nanogels. The particle size, morphology, % entrapment efficiency, FT-IR and x-ray diffraction analysis, in vitro release study and anti-bacterial studies against Staphylococcus aureus and Escherichia coli bacterial strains were evaluated. Spherical shaped particles with transition to amorphous state having a sustained release profiles were evaluated. All the nanogels were assessed for visual examination, spreadability and occlusivity study, rheological measurements, texture analysis, in vitro release, skin irritation, wound healing and histological examinations. Good homogeneity and consistency were found among all the nanogels with having highest viscosity for lawsone loaded nanogel in comparison to blank nanogel. Higher hardness and cohesiveness were observed for lawsone loaded in comparison to blank nanogel showing no skin irritation. In vitro and in vivo results revealed that all the nanogels could be used as effective treatments on the Wistar rats revealing lawsone loaded nanogel had the highest healing on the excision cutaneous wounds showing presence of intact layers of epidermis, granulation tissue, sweat and sebaceous glands, justifying the formulation could be used as an effective treatment in medicine.

Cytotoxicity of Laser-Synthesized Nanoparticles of Elemental Bismuth.

High X-ray absorption combined with photothermal properties make bismuth nanoparticles (Bi NP) a promising agent for multimodal cancer theranostics. However, the synthesis of Bi NP by the "classical" chemical methods has numerous limitations, including potential toxicity of the produced nanomaterials. Here we studied in vitro toxicity of laser-synthesized Bi NP coated with Pluronic F-127 on mouse fibroblast cell line L929. The survival of L929 cells decreased linearly with increasing the concentration of Bi NP in a concentration range of 3-500 μg/ml; the LC50 value was 57 μg/ml. The unique combination of functional properties and moderate toxicity of the laser-synthesized Bi NP makes them a new promising platform for sensitization of multimodal cancer theranostics.

Formulation, characterization and and evaluation of aloe-emodin-loaded solid dispersions for dissolution enhancement.

To prepare aloe-emodin solid dispersion (AE-SD) and determine the metabolic process of AE and AE-SD in vivo. AE-SD was prepared viasolvent evaporation or solvent melting using PEG-6000 and PVP-K30 as carriers. Thermogravimetric analysis, X-ray diffraction spectroscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of AE-SD. Optimal prescriptions were screened viathe dissolution degree determination method. Using Phoenix software, AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo after AE was prepared as a solid dispersion. Acute toxicity was assessed in mice, and the physiological toxicity was used as the determination criterion for toxicity. AE-SD showed that AE existed in the carrier in an amorphous state. Compared with polyethylene glycol, polyvinylpyrrolidone (PVP) inhibited AE crystallization, causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug dispersion. Therefore, it was more suitable as a carrier material for AE-SD. The addition of poloxamer (POL) was more beneficial to the stability of solid dispersions and could reduce the amount of PVP. The dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1：2：2, and its dissolution effect was also optimal. Based on the pharmacokinetic comparison, the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE, the Cmax of AE-SD was greater than that of AE, and t1/2 and mean residence time of AE-SD were less than AE. The results showed that the drug metabolism in AE-SD was better, and the residence time was shorter. The toxicology study showed that both AE and AE-SD had no toxicity. This paper established that the solubility of the drug could be increased after preparing a solid dispersion, as demonstrated by in vitro dissolution experiments. In vivo pharmacokinetics studies confirmed that AE-SD could improve the bioavailability of AE in vivo, providing a new concept for the research and development of AE preparations.

PH-Dependent Lyotropic Liquid Crystalline Mesophase and Ionization Behavior of Phytantriol-Based Ionizable Lipid Nanoparticles.

Self-assembled lipid nanoparticles (LNPs), serving as essential nanocarriers in recent COVID-19 mRNA vaccines, provide a stable and versatile platform for delivering a wide range of biological materials. Notably, LNPs with unique inverse mesostructures, such as cubosomes and hexosomes, are recognized as fusogenic nanocarriers in the drug delivery field. This study delves into the physicochemical properties, including size, lyotropic liquid crystalline mesophase, and apparent pKa of LNPs with various lipid components, consisting of two ionizable lipids (ALC-0315 and SM-102) used in commercial COVID-19 mRNA vaccines and a well-known inverse mesophase structure-forming helper lipid, phytantriol (PT). Two partial mesophase diagrams are generated for both ALC-0315/PT LNPs and SM-102/PT LNPs as a function of two factors, ionizable lipid ratio (α, 0-100 mol%) and pH condition (pH 3-11). Furthermore, the impact of different LNP stabilizers (Pluronic F127, Pluronic F108, and Tween 80) on their pH-dependent phase behavior is evaluated. The findings offer insights into the self-assembled mesostructure and ionization state of the studied LNPs with potentially enhanced endosomal escape ability. This research is relevant to developing innovative next-generation LNP systems for delivering various therapeutics.

Surfactant-induced AIE-active tin(IV) micelles for sensing naproxen residues in pharmaceutical effluents

Nonsteroidal anti-inflammatory drugs, including naproxen (NPX), are highly consumed globally and their prolonged presence in the environment has detrimental effects on human health and aquatic ecosystems. In the present study, fluorescent micelles of thiophene appended chromone-based diorganotin(IV) crystalline solid (TBSn) have been obtained for the spectrofluorimetric detection of NPX in aqueous systems. Two diorganotin(IV) compounds, TBSn and TMSn were obtained from 2-thiocarboxaldehyde substituted 3-hydroxy-benzo-γ-pyrone and characterized by using FT-IR spectroscopy, multi-nuclear NMR (1H, 13C, and 119Sn) spectroscopy, mass spectrometry, CHN elemental analyses, and single-crystal X-ray diffraction. TBSn and TMSn molecules form brickwork architecture via C–H·····Sn, C–H·····O, C–H·····S, and π⋯π contacts which make them insoluble in water. However, the compounds form nano-aggregated AIE-active micelles with the aid of Pluronic F-127 in water. The micellar solution undergoes rapid elevation in emission intensity (within 5–7 s) in the presence of NPX, showcasing its effectiveness in analyzing NPX in the aqueous medium with the detection limit of 0.11 μM with a linear range of 0.5 to 9.5 μM. Therefore, the micellar formulation can be used as an effective chemosensor for the analysis of NPX in aqueous and pharmaceutical samples. This study marks a pioneering achievement in the spectrofluorimetric analysis based on turn-on detection of NPX utilizing TBSn micelles.

Mechanistic Insight in Permeability through Different Membranes in the Presence of Pharmaceutical Excipients: A Case of Model Hydrophobic Carbamazepine.

The present study reports the effects of two pharmaceutical excipients of differing natures-non-ionic surfactant pluronic F127 (F127) and anionic sulfobutylether-β-cyclodextrin (SBE-β-CD)-on the permeation of the model compound, carbamazepine (CBZ). The permeability coefficients of CBZ at three concentrations of the excipients were measured through two different artificial barriers: hydrophilic cellulose membrane (RC) and lipophilic polydimethylsiloxane-polycarbonate membrane (PDS). The equilibrium solubility of CBZ in F127 and SBE-β-CD solutions was determined. The micellization, complexation, and aggregation tendencies were investigated. Systemically increasing the solubility and the reduction of permeation upon the excipients' concentration growth was revealed. The quantitative evaluation of the permeability tendencies was carried out using a Pratio parameter, a quasi-equilibrium mathematical mass transport model, and a correction of permeability coefficients for the free drug concentration ("true" permeability values). The results revealed the mutual influence of the excipient properties and the membrane nature on the permeability variations.

Potential anti-acne loaded nanogel formulations of Origanum majorana L. and Chrysanthemum morifolium Ramat. essential oils

Acne is a highly prevalent skin disease with a great psychological impact on patients as self-perception, self-confidence, and depression. This work aimed to develop an anti-acne preparation from active anti-bacterial medicinal plants to circumvent the severe side effects and drug resistance commonly reported with topical erythromycin anti-acne preparations. Essential oils: Salvia officinalis L. (sage), Rosmarinus officinalis L. (rosemary), Commiphora myrrha Nees Engl. (myrrh), Origanum majorana L. (marjoram), Pelargonium zonale L. L’Hér. ex Aiton (geranium) and Chrysanthemum morifolium Ramat. (chrysanthemum) were extracted by hydrodistillation and analyzed using gas chromatography/mass spectrometry (GC/MS). The anti-acne activities of the oils against Cutibacterium acnes ATCC 6919 were evaluated by microdilution methods to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The most active essential oils were loaded in a film-forming nanogel prepared with chitosan, pluronic F127 and glycerol in the ratio of 3:1:1, prior to investigation in a murine acne in vivo model. Marjoram and chrysanthemum oils showed the highest antimicrobial activity against C. acnes (MIC = 0.156% v/v and 0.125% v/v, respectively). GC/MS of the actives showed that gamma-terpinene (26.46%) and terpinen-4-ol (22.24%) were the predominant constituents in marjoram, whereas chrysanthenone (32.79%) was the main component in chrysanthemum. The formulated essential oil-loaded film-forming nanogels of both oils exhibited significant anti-acne activity in mice via reducing the bacterial loads, activating the antioxidant nuclear factor erythroid 2–related factor 2 (Nrf2) pathway and inhibiting the inflammatory tumor necrosis factor-alpha (TNF-α) pathway. Further studies should be designed to evaluate the clinical evidence for the use of marjoram and chrysanthemum oil products in acne treatment.Graphical

Facile preparation of self-healing hydrogels based on chitosan and PVA with the incorporation of curcumin-loaded micelles for wound dressings

The increased demand for improved strategies for wound healing has, in recent years, motivated the development of multifunctional hydrogels with favorable bio-compatibility and antibacterial properties. To this regard, the current study presented the design of a novel self-healing composite hydrogel that could perform as wound dressing for the promotion of wound healing. The composite hydrogels were composed of polyvinyl alcohol (PVA), borax and chitosan functionalized with sialic acid (SA-CS) and curcumin loaded pluronic F127 micelles. The hydrogels were formed through the boronic ester bond formation between PVA, SA-CS and borax under physiological conditions and demonstrated adjustable mechanical properties, gelation kinetics and antibacterial properties. When incubating with NIH3T3 cells, the hydrogels also demonstrated good biocompatibility. These aspects offer a promising foundation for their prospective applications in developing clinical materials for wound healing.

A theragenerative bio-nanocomposite consisting of black phosphorus quantum dots for bone cancer therapy and regeneration

Recently, the term theragenerative has been proposed for biomaterials capable of inducing therapeutic approaches followed by repairing/regenerating the tissue/organ. This study is focused on the design of a new theragenerative nanocomposite composed of an amphiphilic non-ionic surfactant (Pluronic F127), bioactive glass (BG), and black phosphorus (BP). The nanocomposite was prepared through a two-step synthetic strategy, including a microwave treatment that turned BP nanosheets (BPNS) into quantum dots (BPQDs) with 5 ± 2 nm dimensions in situ. The effects of surfactant and microwave treatment were assessed in vitro: the surfactant distributes the ions homogenously throughout the composite and the microwave treatment chemically stabilizes the composite. The presence of BP enhanced bioactivity and promoted calcium phosphate formation in simulated body fluid. The inherent anticancer activity of BP-containing nanocomposites was tested against osteosarcoma cells in vitro, finding that 150 μg mL−1 was the lowest concentration which prevented the proliferation of SAOS-2 cells, while the counterpart without BP did not affect the cell growth rate. Moreover, the apoptosis pathways were evaluated and a mechanism of action was proposed. NIR irradiation was applied to induce further proliferation suppression on SAOS-2 cells through hyperthermia. The inhibitory effects of bare BP nanomaterials and nanocomposites on the migration and invasion of bone cancer, breast cancer, and prostate cancer cells were assessed in vitro to determine the anticancer potential of nanomaterials against primary and secondary bone cancers. The regenerative behavior of the nanocomposites was tested with healthy osteoblasts and human mesenchymal stem cells; the BPQDs-incorporated nanocomposite significantly promoted the proliferation of osteoblast cells and induced the osteogenic differentiation of stem cells. This study introduces a new multifunctional theragenerative platform with promising potential for simultaneous bone cancer therapy and regeneration.