Controlled Release Research Articles

Injectable and pH-Responsive Metformin-Loaded Hydrogel for Active Inhibition of Posterior Capsular Opacification.

Posterior capsular opacification (PCO) is a common complication following cataract surgery, which can lead to a significant vision loss. This study introduces a facile method for developing a metformin-derived hydrogel (HCM6) stabilized by dynamic covalent bonds among natural polymers. This hydrogel demonstrates antifibrotic properties, on-demand drug release, pH responsiveness, injectability, and self-healing capabilities. Our in vitro experiments confirmed that the HCM6 hydrogel exhibits excellent biocompatibility, inhibiting lens epithelial cell migration, and transforming growth factor-2β (TGFβ2)-induced α-smooth muscle actin (α-SMA) expression in lens epithelial cells. In vivo studies conducted in a rat extracapsular lens extraction (ECLE) model revealed that HCM6 significantly suppressed PCO after 21 days of implantation with no observed pathological effects on surrounding tissues or the optic nerve. According to our experimental results, the inhibitory mechanism of PCO may be attributed to metformin's suppressive effect on lens cell migration, epithelial-mesenchymal transition (EMT), and lens fiber formation. In summary, the long-acting, controllable, and on-demand release characteristics of the HCM6 hydrogel not only provide an effective strategy for preventing PCO but also offer new avenues for treating undesirable proliferative conditions in ophthalmology and beyond.

Development, optimization, and characterization of polymeric micelles to improve dasatinib oral bioavailability: Hep G2 cell cytotoxicity and in vivo pharmacokinetics for targeted liver cancer therapy

The efficacy of dasatinib (DAS) in treating hepatocellular carcinoma (HCC) is hindered by its poor bioavailability, limiting its clinical potential. In this study, we explored the use of TPGS-Soluplus micelles as an innovative drug delivery platform to enhance DAS solubility, stability, and therapeutic impact. A series of TPGS-Soluplus copolymers were synthesized, varying the D-α-tocopheryl polyethylene glycol succinate (TPGS) forms (1000, 2000, and 3500) and adjusting the TPGS to Soluplus weight ratios (1:1, 1:2, and 1:3). Our goal was to identify the optimal formulation with the highest entrapment efficiency, smallest particle size, and enhanced drug loading. The TPGS1000-Soluplus copolymer, with a DAS-to-polymer ratio of 1:30 and a TPGS ratio of 1:2, demonstrated superior performance, achieving an entrapment efficiency of 64.479 ± 1.45 % and drug loading of 5.05 ± 1.01 %. The DAS-loaded micelles (DAS-PMs) exhibited a notably small particle size of 64.479 ± 1.45 nm and demonstrated controlled release kinetics, with 85.60 ± 5.4 % of the drug released over 72 h.Cellular uptake studies using Hep G2 cells revealed significantly enhanced absorption of DAS-PMs compared to free DAS, reflected in lower IC50 values in MTT assays at 24 and 48 h. Pharmacokinetic analysis further highlighted the benefits of the DAS-PMs, with an AUC0-∞ 2.16 times higher and mean residual time (MRT) 1.3 times longer than free DAS, a statistically significant improvement (p < 0.01). These findings suggest that TPGS-Soluplus micelles offer a promising strategy for improving the bioavailability and efficacy of DAS in HCC treatment, presenting a potential new therapeutic avenue for patients with limited options. This innovative formulation could significantly enhance DAS delivery, potentially leading to improved clinical outcomes in liver cancer therapy.

Chitosan xerogel embedded with green synthesized cerium oxide nanoparticle: An effective controlled release fertilizer for improved cabbage growth

With the growing awareness on the adverse effects of conventional fertilizers; the use of sustainable and controlled release fertilizers has garnered much significance. In the present study, we report the synthesis of chitosan-benzaldehyde Schiff base xerogel incorporated with green synthesized cerium oxide nanoparticle using Psidium guajava leaves extract as a sustainable fertilizer. Spherical CeO2 NPs having an average particle size of 15.3 nm and zeta potential of – 39.9 mV was obtained. The urea-loaded nanocomposite xerogel (CsB@U/CeO2) was examined for cabbage growth. The water retention capacity extended for >2 weeks. A controlled release profile for urea was accomplished from CsB@U/CeO2 for a period extending for 30 days. The kinetics assay suggested that presence of CeO2 NPs asserted a greater role in urea-controlled release from the CsB@U/CeO2 nanocomposite hydrogel owing to polymer relaxation. The growth parameters of cabbages such as head height, diameter, fresh head weight, head circumference was enhanced in plants fertilized by CsB@U/CeO2 as compared to urea. Furthermore, the phenolic content, free radical scavenging activity, protein content, sugar and flavonoid content were also found higher in CsB@U/CeO2 fertilized plants. This study puts forth CsB@U/CeO2 xerogel can be potentially harnessed as an alternative to urea in sustainable agriculture.

A NIR light activated self‐reporting carbon dots assembly as phototheranostics for tumor photodynamic therapy

AbstractPhotodynamic therapy (PDT) has emerged as a promising protocol for cancer therapy. However, real‐time monitoring of PDT progress and accurate determination of the optimal treatment timing remain challenges. In this work, we selected carbon dots (CDs) and new indocyanine green (IR820) as building units to fabricate a smart nanotheranostics (CDs‐IR820 assembly) with the characteristics of controlled release and real‐time imaging to solve the time gap between diagnosis and treatment. The fabricated CDs‐IR820 assembly locked the photosensitivity of the CDs and could degrade under 750 nm laser irradiation to achieve controlled release of the CDs, thus used for cell imaging and producing single oxygen under the white light. Besides, the released CDs could migrate from the mitochondria to the nucleus during the PDT process, indicating the cell activity, which facilitated the regulation of treatment parameters to achieve the precise PDT for cancer.

A pH-Responsive Ti-Based Local Drug Delivery System for Osteosarcoma Therapy.

Osteosarcoma is one of the major bone cancers, especially for youngsters. The current treatment usually requires systemic chemotherapy and the removal of bone tumors. Titanium (Ti)-based implants can be modified as local drug delivery (LDD) systems for controllable and localized chemotherapeutic drug release. In this work, a pH-responsive Ti-based LDD prototype was designed by introducing polydopamine (PDA) to release doxorubicin (DOX) around osteosarcoma cells with low pH. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and a contact angle meter were applied for surface characterization. Both direct and indirect cell culture modes were performed for biocompatibility and biofunction assessments. The results indicate that the Ti-based LDD prototype exhibits significant pH-dependent DOX release. The cumulative release can reach up to approximately 40% at pH = 6.0 after 72 h, but only around 20% at pH = 7.4. The Ti-based LDD implant shows good biocompatibility with approximately 93% viability of MC3T3 cells after direct culture in vitro for 24 h. Both direct and indirect culture modes verify the good anti-osteosarcoma function of the LDD implant, which should be attributed to the pH-responsive release of DOX.

Optimizing revision arthroplasty: the role of customized articulating spacers

Introduction The advancement of surgery is set against a backdrop of continuous development and surgical innovations have transformed the way clinical care is delivered. Revision surgery might be required to address complications of primary arthroplasty. The first stage of revision arthroplasty would involve removal of an implant and placement of an antibiotic-impregnated cement spacer to maintain the joint space and stability, prevent soft tissue retraction, provide local antibiotic release and preserve bone tissue for revision implantation at the final stage of revision. Custom-made articulating spacers are a promising tool for optimizing the first stage of revision arthroplasty.The objective was to summarize the current data and present comprehensive information about spacers used in two-stage revision arthroplasty including manufacturing techniques, physical and chemical properties, clinical applications, the possibility of customization within the first stage of revision arthroplasty, current and promising directions for research.Material and methods The original literature search was conducted on key resources including Scientific Electronic Library (www.elibrary.ru), the National Library of Medicine (www.pubmed.org), the Cochraine Library (www.cochranelibrary.com) between 2018 and 2023 using search words and phrases: total arthroplasty, complications, revision arthroplasty, articulating spacer, periprosthetic joint infection, additive manufacturing, 3D printing.Results A comparative analysis of factory supplied, home-made, dynamic and static spacer models showed that the choice of articulating spacers for revision arthroplasty of major joints is of great relevance. Advantages of factory-made spacers include standardized range of sizes, the reliability and availability for medical institutions. They are characterized by limited use in repair of severe bone defects.Discussion Custom-made articulating spacers enable specific tailoring to accommodate individual defects. Despite high expectations from custom-made spacers, development of optimal technologies for rapid prototyping is essential. Investments in research and development in this area have the potential to create innovative solutions that can significantly improve the results of revision arthroplasty.Conclusion The paper explores the importance of systemization of knowledge about spacers and the role of new research in improving the design and functionality. Progress in the field of materials science, additive technologies and a personalized approach to spacer manufacturing can expand possibilities of revision arthroplasty and the effectiveness. Personalized approaches and improved methods of local drug delivery that provide controlled release of antibiotics can improve the results of treatment of periprosthetic joint infections.

Processing Solid Hydrogels into Hollow Structures by Infrared Laser Light for Highly-Efficient Drug Loading and Controlled Release.

Hollow hydrogels, characterized by their three-dimensional networks akin to biological tissues, are extensively utilized in artificial blood vessels, drug delivery, and nerve conduits due to their superior biocompatibility and fluid-transportation capacity. Nonetheless, the fabrication of hollow hydrogels presents significant challenges, including intricate steps, costly equipment, and structural instability. Consequently, refining the preparation techniques for hollow hydrogels remains paramount to surmounting the limitations of conventional methods. This research introduces an innovative approach that markedly diverges from traditional techniques, offering notable convenience and efficiency in the creation of hollow hydrogel structures. The central novelty of this method lies in employing laser light to induce an in situ photothermal effect, leading to the formation of hollow configurations. This laser-driven transformation of solid hydrogels into hollow structures addresses numerous shortcomings associated with traditional methods. For instance, conventional chemical approaches often necessitate several days to yield hollow hydrogels, and the resultant structures tend to be fragile and susceptible to damage under external pressure. In contrast, the laser-assisted technique facilitates the formation of hollow structures within 240 s, significantly outpacing traditional methods. To achieve controlled drug release, silk fibroin was integrated into the wall of the hollow hydrogels, enabling modulation of wall permeability and directing the drug release process.

Gravity-guided snapping sequence in 3D modular multistable metamaterials

The snapping sequence of multistable metamaterials is critical for their applications in elastic wave control and energy release. Despite being a fundamental property, the effect of gravity on the snapping sequence has never been studied. This paper investigates the mechanical mechanism how structural gravity affects the snapping sequence of multistable metamaterials to construct deterministic static and dynamic snapping sequences. A biaxial snap-through availability three-dimensional (3D) modular multistable metamaterial (MMM) is developed. The 3D MMM is assembled from unit cells consisting of a dismountable middle bar (M-bar) and a fixed frame containing two bistable curved beams. Except experimental tests and numerical simulations, analytical analyses are also conducted to verify the snapping sequence induced by gravity in the 3D MMM. In addition, given that the M-bar is dismountable, the effects of its length on the mechanical properties and the impact resistance of the 3D MMM are discussed in detail. It is found that gravity can guide both static and dynamic deterministic snapping sequences of the 3D MMM to optimize the process of elastic wave propagation and energy release, and the proposed 3D MMM can enhance structural impact resistance through elastic deformations.

Light/pH dual controlled drug release "nanocontainer" alleviates tumor hypoxia for synergistic enhanced chemotherapy, photodynamic therapy and chemodynamic therapy

Light/pH dual controlled drug release "nanocontainer" alleviates tumor hypoxia for synergistic enhanced chemotherapy, photodynamic therapy and chemodynamic therapy

Preparation and characterization of high-methoxyl pectin/glycerides emulsion for pH-responsive, targeting, and sustained release of fat-soluble substances

In this study, a pH-responsive emulsion system was prepared, combining high-methoxyl pectin (HMP) with camellia oil glycerides (CG). The emulsion was characterized as O/W type, with HMP serving as the wall material and CG as the oil phase. The physicochemical properties, pH responsiveness, digestion stability, and encapsulated delivery capabilities of the HMP-CG emulsion were investigated. The emulsion showed an average droplet size of 480.47 ± 76.19 nm, possessing a negative charge and a pronounced core-shell structure. HMP package CG enhanced hydrophilic ability and enabled targeted release within the small intestine through the structural changes of HMP. The presence of HMP and CG increased droplet dispersion and target digestibility of the emulsion system, leading to sustainable small intestine-specific release. Overall, HMP-CG emulsion system, composed of natural materials, exhibited the ability to achieve targeted and controllable release via pH-responsive mechanisms, offering an alternative for developing gel materials incorporating fat-soluble substances.

RABV antigenic peptide loaded polymeric nanoparticle production, characterization, and preliminary investigation of its biological activity

Nanoparticle-based antigen carrier systems have become a significant area of research with the advancement of nanotechnology. Biodegradable polymers have emerged as particularly promising carrier vehicles due to their ability to address the limitations of existing vaccine systems. In this study, we successfully encapsulated the G5-24 linear peptide, located between amino acids 253 and 275 in the primary sequence of the rabies virus G protein, into biodegradable and biocompatible PLGA copolymer using the double emulsion solvent evaporation method. The resulting nanoparticles had a size of approximately 230.9 ± 0.9074 nm, with a PDI value of 0.168 ± 0.017 and a zeta potential value of -9.86 ± 0.132 mV. SEM images confirmed that the synthesized nanoparticles were uniform in size and distribution. Additionally, FTIR spectra indicated successful peptide loading into the nanoparticles. The encapsulation efficiency of the peptide-loaded nanoparticles was 73.3%, with a peptide loading capacity of 48.2% and a reaction yield of 30.4%. Peptide release studies demonstrated that 65.55% of the peptide was released in a controlled manner over 28 d, following a 'biphasic burst release' profile consistent with the degradation profile of PLGA. This controlled release is particularly beneficial for vaccine studies. Cytotoxicity tests revealed that the R-NP formulation did not induce cytotoxicity in fibroblast cells and enhanced NO production in macrophages, indicating its potential for vaccine development.

Electrospun poly(N-vinylpyrrolidone) membranes with Ag nanoparticles for wound dressings: Production and characterization

Wound dressings have long been used to promote the healing of skin injuries. In the work reported here, fibrous membranes were produced by electrospinning poly(N-vinylpyrrolidone) (PVP) solutions containing silver nitrate at varying mass ratios (1:200, 1:100 and 1:50 AgNO3:PVP). PVP solutions without AgNO3 were used as a control. The electrospun membranes were irradiated using 254 nm UV light to simultaneously photo-crosslink PVP and promote the formation of silver nanoparticles (AgNPs). The formation of AgNPs was confirmed by scanning electron microscopy and transmission electron microscopy, as well as by detecting the surface plasmon resonance peak at 420 nm in the UV–Vis spectrum during release studies. The swelling rate of fibrous membranes was lower for those containing AgNPs compared to PVP-only membranes. The Kirby-Bauer diffusion test performed against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Candida albicans showed that all AgNPs-containing membranes exhibited an inhibitory effect on all microorganisms tested. The in vitro cytotoxicity assay showed that membranes with lower silver concentration were less cytotoxic. This study presents a simple route to producing a wound dressing with antimicrobial action that has a swelling behavior capable of absorbing exudates, provides controlled release of silver and has low cytotoxicity.

Development of a new micellar formulation of carvedilol and curcumin to enhance blood pressure reduction in a spontaneously hypertensive rat model.

Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide, requiring innovative therapeutic strategies. This project explores a nano-pharmaceutical approach to enhance the efficacy of cardiovascular drugs, focusing on carvedilol and curcumin. These agents, known for their potential cardiovascular benefits, are encapsulated within Soluplus® micelles to form a novel drug delivery system. The novelty of this formulation lies in its ability to significantly improve the solubility of both carvedilol and curcumin, which have traditionally been limited by their hydrophobic nature. By utilizing Soluplus® micelles, we have developed a unique delivery system that optimizes the therapeutic potential of both drugs. The nanomicelles were meticulously characterized for drug loading, size distribution, and morphological features. The carvedilol and curcumin release patterns were investigated, revealing sustained and controlled release profiles. Additionally, the antioxidant capacity of the micellar formulation was evaluated, demonstrating the preservation of curcumin's antioxidative properties. In vivo studies using spontaneously hypertensive male rats explored the pharmacokinetics and hemodynamic effects of the nanomicellar system. These results indicated successful encapsulation of both drugs without altering their plasma profiles. Furthermore, the administration of carvedilol and curcumin micelles exhibited a more significant reduction in mean arterial pressure compared to individual drug administration, suggesting a potential synergistic effect. In conclusion, this nano-pharmaceutical approach offers a promising avenue for cardiovascular therapy, providing a platform for combined drug delivery and potential synergistic effects. The optimized formulation could lead to improved patient outcomes and enhanced cardiovascular health.

Cu-doped calcium phosphate supraparticles for bone tissue regeneration.

Calcium phosphate (CaP) minerals have shown great promise as bone replacement materials due to their similarity to the mineral phase of natural bone. In addition to biocompatibility and osseointegration, the prevention of infection is crucial, especially due to the high concern of antibiotic resistance. In this context, a controlled drug release as well as biodegradation are important features which depend on the porosity of CaP. An increase in porosity can be achieved by using nanoparticles (NPs), which can be processed to supraparticles, combining the properties of nano- and micromaterials. In this study, Cu-doped CaP supraparticles were prepared to improve the bone substitute properties while providing antibacterial effects. In this context, a modified sol-gel process was used for the synthesis of CaP NPs, where a Ca/P molar ratio of 1.10 resulted in the formation of crystalline β-tricalcium phosphate (β-TCP) after calcination at 1000 °C. In the next step, CaP NPs with Cu2+ (0.5-15.0 wt%) were processed into supraparticles by a spray drying method. Cu release experiments of the different Cu-doped CaP supraparticles demonstrated a long-term sustained release over 14 days. The antibacterial properties of the supraparticles were determined against Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, where complete antibacterial inhibition was achieved using a Cu concentration of 5.0 wt%. In addition, cell viability assays of the different CaP supraparticles with human telomerase-immortalized mesenchymal stromal cells (hMSC-TERT) exhibited high biocompatibility with particle concentrations of 0.01 mg mL-1 over 72 hours.

Review of Lipid Nanoparticles for Breast Cancer Management: Targeting Strategies and Clinical Perspective

Abstract: Chemotherapy, a conventional breast cancer treatment, has limitations due to its nonspecific mechanisms and undesirable side effects. Lipid-based nanoparticles (LNPs) have emerged as a versatile and superior platform for targeted breast cancer treatment, offering several distinct advantages over traditional therapies. This class of nanocarriers, which includes solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and liposomes, enhances the bioavailability and stability of therapeutic agents while minimizing systemic toxicity. LNPs can be engineered to precisely target breast cancer cells by exploiting tumor-specific markers, enabling selective delivery of chemotherapeutic agents and reducing off-target effects. SLNs provide controlled drug release and improved drug retention within the tumor, while NLCs offer higher drug-loading capacities and better stability. Liposomes, with their flexible design, allow for the encapsulation of both hydrophilic and hydrophobic drugs and can be modified for active targeting through surface functionalization. These lipid-based carriers also address the challenges of multi-drug resistance (MDR) by enhancing intracellular drug concentration and overcoming efflux mechanisms. In this review, we focus on lipid-based nanoparticles- a subtype of nanoparticles, and their potential advantages as drug delivery systems for breast cancer treatment. Results revealed that lipidbased nanoparticles have shown potential in breast cancer management, these include improved drug efficacy, enhanced ability to overcome cancer therapy resistance, and effective drug carrier for co-loaded drugs.

Preparation of ternary hybridized chitosan microspheres with photothermal effect for pH-sensitive long-lasting controlled release system and its release mechanism

To enhance the effective utilization of drugs and diminish the number of medications for patients, it is vital to investigate controlled long-acting drug release systems and their release mechanisms. In this study, chitosan microspheres were synthesized by cross-linking pH-sensitive Schiff bases, and Zif-8, a pH-sensitive component, was encapsulated within them. Furthermore, MXene was incorporated as a third component to augment the strength and photothermal synergistic characteristics of the microspheres. By adjusting the ratio of each component, the optimal ternary heterogeneous functional pH-controllable long-lasting drug release system was obtained. The optimal coating and the most effective adsorption-release effect were achieved. The release mechanism was examined under varying pH and temperature conditions. The release process was found to be divided into three stages. The initial phase was predominantly governed by the Fick diffusion mechanism, whereas the subsequent phases were primarily regulated by the pH-induced co-decomposition of CS and Zif-8, and the individual decomposition of CS, respectively.The drug was observed to be released in a linear manner during the latter two stages of the experiment. This was evidenced by the persistent release of ciprofloxacin hydrochloride in response to pH changes, and further supported by the results of tests on its antimicrobial properties. The drug release persisted for over three days at pH 5.4 and could be utilized repeatedly, exhibiting promising applications in drug delivery. Moreover, the drug's photothermal properties offer the possibility of developing synergistic therapeutic programs.

PLGA/Ti-Zn as Nanocomposite for Drug Delivery of Oleoresin

Capsicum annuum L. var. “Chile de árbol” combined with poly(lactic-co-glycolic acid) (PLGA) and TiO2-ZnO oxides synthesized at different molar ratios and pH (Ti-Zn A and B 3:1, 1:1, and 1:3) via the sol-gel method was characterized by the Brunauer–Emmett–Teller (BET) method, a UV-Vis spectrophotometer (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), High-Performance Liquid Chromatography (HPLC-DAD), and a release profile through mathematical models to explain its behavior. Furthermore, FTIR revealed the presence of PLGA, TiO2, and ZnO as well as amino group characteristics from oleoresin components, principally alkaloid groups (capsaicin and dihydrocapsaicin), as evidenced by HPLC, to identify the presence of capsaicin and dihydrocapsaicin. The UV-Vis spectra showed a slight hypsochromic shift in the PLGA treatments. The release profile demonstrated a higher controllable release in the PLGA treatments than in the double nanoemulsions. Moreover, it is important to note that the effect of NPs influenced the release profile itself, increasing the release when NPs were synthesized at an acidic pH. Therefore, the TiZnOl/PLGA A characteristics suggest that these results have potential for pharmaceutical (as drug carriers) and medical applications.

Chemical Composition, Antioxidant, Antibacterial, and Hemolytic Properties of Ylang-Ylang (Cananga odorata) Essential Oil: Potential Therapeutic Applications in Dermatology

Background/Objectives: This study investigates the chemical composition, antioxidant, antibacterial, and hemolytic properties of ylang-ylang (Cananga odorata) essential oil, with a focus on its potential therapeutic applications for dermatological diseases and the importance of transforming such bioactive properties into a stable, safe, and effective formulation. Methods/Rsults: Essential oils were extracted from flowers harvested in northern Grande Comore using hydro distillation at three different distillation times to examine the impact on yield and quality. Gas chromatographic analysis identified a complex mixture of compounds, including linalool, geranyl acetate, and benzyl benzoate. Antioxidant activity was assessed using DPPH, FRAP, TAC, and beta-carotene bleaching inhibition assays, revealing significant radical scavenging capabilities, with DPPH IC50 varying between 1.57 and 3.5 mg/mL. Antibacterial activity was tested against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa, showing promising inhibition zones and minimum inhibitory concentrations. Hemolytic tests indicated varying degrees of red blood cell damage, emphasizing the need for careful concentration management in therapeutic applications. Molecular docking studies highlighted potential therapeutic targets for dermatological conditions, identifying high binding affinities for specific compounds against proteins involved in acne, eczema, and psoriasis. Conclusions: This comprehensive analysis underscores the potential of ylang-ylang essential oil (YEOs) as a natural alternative for antimicrobial treatments and dermatological applications, with its success dependent on optimized extraction methods and precise formulation to reduce cytotoxic effects. A formulation approach is crucial to ensure controlled release, improve bioavailability, and minimize skin irritation.

A Targeted Click-to-Release Activation of the Last-Resort Antibiotic Colistin Reduces its Renal Cell Toxicity.

The use of highly potent but very toxic antibiotics such as colistin has become inevitable due to the rise of antimicrobial resistance. We aimed for a chemically-triggered, controlled release of colistin at the infection site to lower its systemic toxicity by harnessing the power of click-to-release reactions. Kinetic experiments with nine tetrazines and three dienophiles demonstrated a fast release via an inverse-electron-demand Diels-Alder reaction between trans-cyclooctene (TCO) and the amine-functionalised tetrazine Tz7. The antibiotic activity of colistin against Escherichia coli was masked by TCO units, but restored upon reaction with d-Ubi-Tz, a tetrazine functionalised with the bacterial binding peptide d-Ubi29-41. While standard TCO did not improve toxicity against human proximal tubular kidney HK-2 cells, the installation of an aspartic acid-modified TCO masking group reduced the overall charge of the peptide and entry to the kidney cells, thereby dramatically lowering its toxicity. The analog Col-(TCO-Asp)1 had favourable pharmacokinetic properties in mice and was successfully activated locally in the lung by d-Ubi-Tz in an in vivo infection model, whereas it remained inactive and non-harmful without the chemical trigger. This study constitutes the first example of a systemically acting two-component antibiotic with improved drug tolerability.

Triethanolamine-modified poloxamer temperature-sensitive hair care gel for intelligent controlled release of sodium thioglycolat

Abstract A triethanolamine-modified poloxamer temperature-sensitive hair care gel was formulated in order to reduce the adverse health effects associated with sodium thioglycolate (TGA(Na)), the active component in hair treatment agents, while maintaining excellent efficacy. It was found that TEA-3 gelled at 32 °C with a triethanolamine concentration of 3 %. This formulation exhibited a reversible phase transition, transitioning to a solid state upon contact with the scalp (&gt;32 °C) and reverting to a liquid state when in contact with hair (&lt;32 °C). The release behavior of TGA(Na) from the gel was assessed by both in vitro release studies and transdermal experiments. In addition, it was observed that the triethanolamine-modified poloxamer gel exhibited improved hair care efficiency compared to conventional hair care agents. These results suggest that the triethanolamine-modified poloxamer gel is a promising alternative to conventional hair care products, offering improved efficacy while minimizing potential adverse health effects.