Search Results (27)

The stability of cement slurries under high-temperature conditions poses a significant engineering challenge in cementing operations. This study explored the development of a novel tetrameric thermosensitive thickening polymer (TTSTC) as a solution to this problem. Aqueous free radical polymerization was employed to synthesize the polymer. The base monomers 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and acrylamide (AM) were employed, in conjunction with the long-chain thermosensitive monomers octadecyldimethylallylammonium chloride (C18DMAAC) and N-vinylpyrrolidone (NVP). The optimal synthesis conditions were determined by orthogonal experiments as follows: monomer molar ratio (AM:AMPS:C18DMAAC:NVP) = 15:10:5:5, initiator concentration of 16 wt%, cross-linker concentration of 0.45 wt%, pH 6, and polymerization temperature of 60 °C. The chemical structure of TTSTC was characterized by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H-NMR), gel permeation chromatography, scanning electron microscopy, Zeta potential, and particle size measurement. The results verified the successful synthesis of the target polymer. Its thermal stability, thermosensitive thickening behavior, and salinity resistance were systematically investigated. Furthermore, the impact of TTSTC on the settling stability, rheological characteristics, and compressive strength of cement paste was assessed. The experimental findings demonstrated that TTSTC displayed noteworthy thermosensitive thickening properties at temperatures up to 279 °C, pH values ranging from 11 to 13, and NaCl/CaCl₂ concentrations between 0.05 and 0.5 g/L. The optimal performance of TTSTC was observed at mass fractions ranging from 0.6 to 0.8 wt%. When incorporated into the slurry at 0.6–1.0 wt%, TTSTC significantly improved the slurry settling stability, thickening properties, and 28d compressive strength at elevated temperatures compared with the control. When comparing the temperature-sensitive thickening performance of the newly developed treatment agent with that of the commercially available xanthan gum thickener, the results showed that for the cement slurry system containing the new treatment agent at a mass fraction of 0.6%, the reduction in consistency was 30.9% less than that of the cement slurry system with xanthan gum at a mass fraction of 0.6%. These findings indicate that TTSTC has the potential to function as a highly effective additive in cementing operations conducted in extreme environments, thereby enhancing the stability and dependability of such operations. Full article

Objectives: Thermo-gelling hydrophilic polymers like PLGA–PEG–PLGA are known as injectable sustained-release depots for biologics, but they face challenges due to the occurrence of severe burst release. This study aimed to develop a strategy to avoid the initial burst release by pre-encapsulating proteins in polysaccharide microparticles through an aqueous–aqueous emulsion mechanism, thereby enhancing therapeutic retention and linear release kinetics. Methods: Five model proteins (G-CSF, GM-CSF, IGF-1, FVIII, BSA) were encapsulated in dextran microparticles, using an organic solvent-free aqueous–aqueous emulsion method. These particles were dispersed in a 23% (w/w) PLGA–PEG–PLGA solution and injected into a 37 °C release buffer to form a gel depot. The in vitro release profiles were quantified using ELISA and MicroBCA assays over 9–42 days. The bioactivity of the proteins was validated using cell proliferation assays (NFS-60, TF-1, MCF-7) and chromogenic kits. The in vivo pharmacokinetics of the FVIII-loaded formulations were evaluated in Sprague–Dawley rats (n = 5/group) over 28 days. Results: Protein-loaded dextran particles retained their structural integrity within the hydrogel and exhibited minimal burst release (≤5% within 30 min vs. >25% for free proteins). Sustained near-linear release profiles were observed for all the proteins, with complete release by day 9 (G-CSF, GM-CSF, BSA) or day 42 (FVIII). Rats administered with the thermal gel with FVIII–dextran particles showed a significantly lower peak plasma concentration (C_max: 88.25 ± 30.21 vs. 132.63 ± 66.67 ng/mL) and prolonged therapeutic coverage (>18 days vs. 15 days) compared to those administered with the thermal gel with the FVIII solution. The bioactivity of the released proteins remained at ≥90% of the native forms. Conclusions: Pre-encapsulation in dextran microparticles effectively mitigates burst release from thermosensitive hydrogels, while preserving protein functionality. Full article

Background/Objectives: Curcumin (CUR) is a natural compound with notable antitumor properties but faces limitations in topical applications due to poor aqueous solubility, instability, and insufficient skin penetration. To overcome these challenges, a nanomicellar formulation (TPGS30ELP15) was developed to enhance CUR solubility, stability, and skin penetration. This study aimed at evaluating the skin permeation and retention of CUR when delivered through nanomicelles alone or combined with a thermosensitive hydrogel for potential melanoma therapy. Methods: A CUR-loaded nanomicellar formulation containing CUR 5 mM was developed, characterized by particle sizes of 12–25 nm. Skin permeation studies utilized pig ear skin to assess CUR localization using both HPLC quantitative analysis and confocal microscopy. To improve patient comfort and application efficiency, the nanomicellar dispersion was incorporated into a thermosensitive hydrogel based on 16% Kolliphor^® P407 and was able to undergo a sol–gel transition at skin temperature (32–36 °C). Formulations were evaluated for physicochemical properties, stability, and CUR distribution within skin layers using in vitro permeation assays. Results: CUR-loaded nanomicelles demonstrated selective localization in the viable epidermis (100–150 µm depth), bypassing the stratum corneum. The addition of the thermosensitive hydrogel enhanced CUR retention and distribution, prolonging contact at the application site and providing a gradual release profile. The hydrogel’s sol–gel transition properties can facilitate ease of use and patient compliance. The combined system effectively delivered CUR to the basal epidermis, a target site for melanoma treatment, achieving therapeutically relevant drug concentrations. Conclusions: The incorporation of CUR-loaded nanomicelles into a thermosensitive hydrogel enhanced the solubility, stability, and targeted delivery of CUR to skin layers. This dual system represents a promising strategy for improving topical drug delivery for melanoma therapy, addressing limitations associated with CUR’s physicochemical properties while ensuring patient-friendly application and gradual drug release. Full article

Fungal keratitis is a severe ocular infection caused by pathogenic fungi, leading to potential vision loss if untreated. Current antifungal treatments face limitations such as low solubility, poor corneal penetration, and limited therapeutic options. This study aimed to develop a thermosensitive in situ gel incorporating ketoconazole nanoparticles (NPs) to enhance drug solubility, stability, and antifungal activity. Ketoconazole NPs were prepared using the solvent displacement method, achieving a particle size of 198.25 ± 27.51 nm, encapsulation efficiency of 94.08 ± 0.51%, polydispersity index of 0.42 ± 0.08, and a positive zeta potential value of +10.08 ± 0.19 mV. The NPs exhibited sustained zero-order release kinetics. The optimized NPs were incorporated into a poloxamer-based in situ gel, demonstrating a gelation temperature of 34.67 ± 0.58 °C and the shortest gelation time. The formulation provided a 5-fold increase in solubility and a 10-fold improvement in drug release compared to pure ketoconazole. Stability studies confirmed the gel retained its physicochemical and rheological properties for three months under various storage conditions. The in situ gel showed sustained release, effective antifungal activity against Malassezia furfur, and good tolerability, suggesting it as a promising alternative for treating fungal keratitis with improved bioavailability and patient compliance. Full article

Nebivolol hydrochloride (NEB), a 3rd-generation beta-blocker, was recently explored in managing open-angle glaucoma due to its mechanism of action involving nitric oxide release for the vasodilation. To overcome the issue of low ocular bioavailability and the systemic side effects associated with conventional ocular formulation (aqueous suspension), we designed and optimized polycaprolactone polymeric nanoparticles (NEB-PNPs) by applying design of experiments (DoE). The particle size and drug loading of the optimized NEB-PNPs were 270.9 ± 6.3 nm and 28.8 ± 2.4%, respectively. The optimized NEB-PNPs were suspended in a dual-sensitive in situ gel prepared using a mixture of P407 + P188 (as a thermo-sensitive polymer) and κCRG (as an ion-sensitive polymer), reported previously by our group. The NEB-PNPs-loaded in situ gel (NEB-PNPs-ISG) formulation was characterized for its rheological behavior, physical and chemical stability, in vitro drug release, and in vivo efficacy. The NEB-PNPs-loaded in situ gel, in ocular pharmacokinetic studies, achieved higher aqueous humor exposure (AUC_0–t = 329.2 ng × h/mL) and for longer duration (mean residence time = 9.7 h) than compared to the aqueous suspension of plain NEB (AUC_0–t = 189 ng × h/mL and mean residence time = 6.1 h) reported from our previous work. The pharmacokinetic performance of NEB-PNPs-loaded in situ gel translated into a pharmacodynamic response with 5-fold increase in the overall percent reduction in intraocular pressure by the formulation compared to the aqueous suspension of plain NEB reported from our previous work. Further, the mean response time of NEB-PNPs-loaded in situ gel (12.4 ± 0.6 h) was three times higher than aqueous suspension of plain NEB (4.06 ± 0.3 h). Full article

Iron deficiency anemia (IDA) presents a global health challenge, impacting crucial development stages in humans and other mammals. Pigs, having physiological and metabolic similarities with humans, are a valuable model for studying and preventing anemia. Commonly, a commercial iron dextran formulation (CIDF) with iron dextran particles (IDPs) is intramuscularly administered for IDA prevention in pigs, yet its rapid metabolism limits preventive efficacy. This study aimed to develop and evaluate chitosan thermosensitive hydrogels (CTHs) as a novel parenteral iron supplementation strategy, promoting IDPs’ prolonged release and mitigating their rapid metabolism. These CTHs, loaded with IDPs (0.1, 0.2, and 0.4 g of theoretical iron/g of chitosan), were characterized for IM iron supplementation. Exhibiting thermosensitivity, these formulations facilitated IM injection at ~4 °C, and its significant increasing viscosity at 25–37 °C physically entrapped the IDPs within the chitosan’s hydrophobic gel without chemical bonding. In vitro studies showed CIDF released all the iron in 6 h, while CTH0.4 had a 40% release in 72 h, mainly through Fickian diffusion. The controlled release of CTHs was attributed to the physical entrapment of IDPs within the CTHs’ gel, which acts as a diffusion barrier. CTHs would be an effective hydrogel prototype for prolonged-release parenteral iron supplementation. Full article

Gel-immobilized colloidal amorphous structures comprise short-range-ordered monodisperse submicrometer particles embedded into a soft polymer gel. They exhibit an angle-independent structural color that is tunable in response to external stimuli via a volume change in the gel, which has significant potential for the development of sensors that respond to stimuli via angle-independent color changes. In this study, the amorphous structure of a charged colloidal suspension in water was immobilized in a thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) gel film and simultaneously attached to a polyethylene terephthalate (PET) substrate. The gel film exhibited a uniform angle-independent color that changed in response to changes in temperature (i.e., thermosensitivity). Attachment to the PET substrate suppressed changes in the gel film area and film distortion, despite significant volume changes in the gel. Consequently, the degree of thermosensitivity was enhanced. The PET-attached gel-immobilized colloidal amorphous film was easy to handle and had excellent flexibility, allowing it to wrap around the surfaces of curved objects. These features are advantageous for sensor applications. Full article

Biocompatible particle-stabilized emulsions have gained significant attention in the biomedical industry. In this study, we employed dynamic high-pressure microfluidization (HPM) to prepare a biocompatible particle emulsion, which effectively enhances the thermal stability of core materials without the addition of any chemical additives. The results demonstrate that the HPM-treated particle-stabilized emulsion forms an interface membrane with high expansion and viscoelastic properties, thus preventing core material agglomeration at elevated temperatures. Furthermore, the particle concentration used for constructing the emulsion gel network significantly impacts the overall strength and stability of the material while possessing the ability to inhibit oxidation of the thermosensitive core material. This investigation explores the influence of particle concentration on the stability of particle-stabilized emulsion gels, thereby providing valuable insights for the design, improvement, and practical applications of innovative clean label emulsions, particularly in the embedding and delivery of thermosensitive core materials. Full article

Background: Cervical intraepithelial neoplasia, the predisposing factor for cervical cancer (CC), is caused by human papillomavirus (HPV) infection and can be treated with imiquimod (IMQ). However, poor water solubility and side effects such as local inflammation can render IMQ ineffective. The aim of this study is to design a prolonged release nano system in combination with mucoadhesive–thermosensitive properties for an effective vaginal drug delivery. Methods: Polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), poly lactide-co-caprolactone (PLA-PCL), and poly L-lactide-co-caprolactone-co-glycolide (PLGA-PCL) were used to create IMQ nanoparticles. Chitosan (CS) was then added to the surfaces of the IMQ NPs for its mucoadhesive properties. The NPs were then incorporated into poloxamer hydrogels. The NPs’ size and morphology, encapsulation efficiency (EE), in vitro drug release, gel characterization, ex vivo drug permeation, and in vitro safety and efficacy were characterized. Results: Two batches of NPs were prepared, IMQ NPs and CS-coated NPs (CS-IMQ NPs). In general, both types of NPs were uniformly spherical in shape with average particle sizes of 237.3 ± 4.7 and 278.2 ± 5.4 nm and EE% of 61.48 ± 5.19% and 37.73 ± 2.88 for IMQ NPs and CS-IMQ NPs, respectively. Both systems showed prolonged drug release of about 80 and 70% for IMQ NPs and CS-IMQ NPs, respectively, within 48 h. The gelation temperatures for the IMQ NPs and CS-IMQ NPs were 30 and 32 °C, respectively; thus, suitable for vaginal application. Although ex vivo permeability showed that CS-IMQ NPs showed superior penetration compared to IMQ NPs, both systems enhanced drug penetration (283 and 462 µg/cm² for IMQ NPs and CS-IMQ NPs, respectively) relative to the control (60 µg/cm²). Both systems reduced the viability of cervical cancer cells, with a minimal effect of the normal vaginal epithelium. However, IMQ NPs exhibited a more pronounced cytotoxic effect. Both systems were able to reduce the production of inflammatory cytokines by at least 25% in comparison to free IMQ. Conclusion: IMQ and CS-IMQ NP in situ gels enhanced stability and drug release, and improved IMQ penetration through the vaginal tissues. Additionally, the new systems were able to increase the cytotoxic effect of IMQ against CC cells with a reduction in inflammatory responses. Thus, we believe that these systems could be a good alternative to commercial IMQ systems for the management of CC. Full article

A keloid is a benign tumor manifested as abnormal fibroplasia on the surface of the skin. Curing keloids has become a major clinical challenge, and searching for new treatments and medications has become critical. In this study, we developed a LA67 liposome-loaded thermo-sensitive hydrogel (LA67-RL-Gel) with active targeting for treating keloids via peritumoral injection and explored the anti-keloid mechanism. Firstly, Arg-Gly-Asp (RGD) peptide-modified liposomes (LA67-RL) loaded with LA67 were prepared with a particle size of 105.9 nm and a Zeta potential of −27.4 mV, and an encapsulation efficiency of 89.6 ± 3.7%. We then constructed a thermo-sensitive hydrogel loaded with LA67-RL by poloxamer 407 and 188. The formulation was optimized through the Box–Behnken design, where the impact of the proportion of the ingredients on the quality of the hydrogel was evaluated entirely. The optimal formulation was 20.7% P407 and 2.1% P188, and the gelation time at 37 °C was 9.5 s. LA67-RL-Gel slowly released 92.2 ± 0.8% of LA67 at pH 6.5 PBS for 72 h. LA67-RL-Gel increased adhesion with KF cells; increased uptake; promoted KF cells apoptosis; inhibited cell proliferation; reduced α-SMA content; decreased collagen I, collagen III, and fibronectin deposition; inhibited angiogenesis; and modulated the keloid microenvironment, ultimately exerting anti-keloid effects. In summary, this simple, low-cost, and highly effective anti-keloid liposome hydrogel provides a novel approach for treating keloids and deserves further development. Full article

The present study investigates the brain-targeted efficiency of atomoxetine (AXT)-loaded nanostructured lipid carrier (NLC)-laden thermosensitive in situ gel after intranasal administration. AXT-NLC was prepared by the melt emulsification ultrasonication method and optimized using the Box–Behnken design (BBD). The optimized formulation (AXT-NLC) exhibited particle size PDI, zeta potential, and entrapment efficiency (EE) of 108 nm, 0.271, −42.3 mV, and 84.12%, respectively. The morphology of AXT-NLC was found to be spherical, as confirmed by SEM analysis. DSC results displayed that the AXT was encapsulated within the NLC matrix. Further, optimized NLC (AXT-NLC13) was incorporated into a thermosensitive in situ gel using poloxamer 407 and carbopol gelling agent and evaluated for different parameters. The optimized in situ gel (AXT-NLC13G4) formulation showed excellent viscosity (2532 ± 18 Cps) at 37 °C and formed the gel at 28–34 °C. AXT-NLC13-G4 showed a sustained release of AXT (92.89 ± 3.98% in 12 h) compared to pure AXT (95.47 ± 2.76% in 4 h). The permeation flux through goat nasal mucosa of AXT from pure AXT and AXT-NLC13-G4 was 504.37 µg/cm²·h and 232.41 µg/cm²·h, respectively. AXT-NLC13-G4 intranasally displayed significantly higher absolute bioavailability of AXT (1.59-fold higher) than intravenous administration. AXT-NLC13-G4 intranasally showed 51.91% higher BTP than pure AXT (28.64%) when administered via the same route (intranasally). AXT-NLC13-G4 showed significantly higher BTE (207.92%) than pure AXT (140.14%) when administered intranasally, confirming that a high amount of the AXT reached the brain. With the disrupted performance induced by L-methionine, the AXT-NLC13-G4 showed significantly (p < 0.05) better activity than pure AXT as well as donepezil (standard). The finding concluded that NLC in situ gel is a novel carrier of AXT for improvement of brain delivery by the intranasal route and requires further investigation for more justification. Full article

Most injectable preparations for the articular cavity are solution-type preparations that are frequently administered because of rapid elimination. In this study, triptolide (TPL), an effective ingredient in the treatment of rheumatoid arthritis (RA), was prepared in the form of a nanoparticle thermosensitive gel (TPL-NS-Gel). The particle size distribution and gel structure were investigated by TEM, laser particle size analysis and laser capture microdissection. The effect of the nanoparticle carrier material PLGA on the phase transition temperature was investigated by ¹H variable temperature NMR and DSC. The tissue distribution, pharmacokinetic behavior, four inflammatory factors and therapeutic effect were determined in a rat RA model. The results suggested that PLGA increased the gel phase transition temperature. The drug concentration of the TPL-NS-Gel group in joint tissues was higher than that in other tissues at different time points, and the retention time was longer than that of the TPL-NS group. After 24 days of administration, TPL-NS-Gel significantly improved the joint swelling and stiffness of the rat models, and the improvement degree was better than that of the TPL-NS group. TPL-NS-Gel significantly decreased the levels of hs-CRP, IL-1, IL-6 and TNF-α in serum and joint fluid. There was a significant difference between the TPL-NS-Gel and TPL-NS groups on Day 24 (p < 0.05). Pathological section results showed that inflammatory cell infiltration was lower in the TPL-NS-Gel group, and no other obvious histological changes were observed. Upon articular injection, the TPL-NS-Gel prolonged drug release, reduced the drug concentration outside the articular tissue and improved the therapeutic effect in a rat RA model. The TPL-NS-Gel can be used as a new type of sustained-release preparation for articular injection. Full article

Thermosensitive gels based on copolymers (PEG–chitosan, chitosan–polyethylenimine, chitosan–arginine and glycol–chitosan–spermine) are presented as promising polycations for the formation of DNA polyplexes and the potential for the development of drugs with prolonged release (up to 30 days). Being in liquid form at room temperature, such compounds can be injected into muscle tissue with rapid gel formation at human body temperature. An intramuscular depot is formed with a therapeutic agent that provides a gradual release of the drug, such as an antibacterial or cytostatic. The physico-chemical parameters of the formation of polyplexes between polycationic polymers of various compositions and molecular architecture and DNA were studied via FTIR, UV-vis and fluorescence spectroscopy using the dyes rhodamine 6G (R6G) and acridine orange (AO). The competitive displacement of AO from AO-DNA complexes showed that, with a ratio of N/P = 1, most of the DNA is bound to a polycation. During the formation of polyplexes, the DNA charge is neutralized by a polycation, which is reflected in electrophoretic immobility. The cationic polymers described in this work at a concentration of 1–4% are capable of forming gels, and the thermoreversible property is most characteristic of pegylated chitosan. BSA, as a model anionic molecule, is released by half in 5 days from the Chit5-PEG5 gel; full release is achieved in 18–20 days. At the same time, in 5 days, the gel is destroyed up to 30%, and in 20 days, by 90% (release of chitosan particles). For the first time, flow cytometry was used to study DNA polyplexes, which showed the existence of fluorescent particles in a much larger number in combination with free DNA. Thus, functional stimulus-sensitive polymers are potentially applicable for the creation of prolonged therapeutic formulations for gene delivery systems, which were obtained. The revealed regularities appear to be a platform for the design of polyplexes with controllable stability, in particular, fulfilling the requirements imposed for gene delivery vehicles. Full article

Super absorbent resin particles used as profile control and water plugging agent remains a deficiency that the particles swells with high speed when absorbing water, resulting in low strength and limited depth of migration. To address this issue, we proposed a thermosensitive particle gel possessing the upper critical solution temperature (UCST), which was synthesized from hydrophobically modified poly(vinyl alcohol)s (PVA) with glutaraldehyde (GA) as a cross-linker. The structure of the hydrogel was characterized by Fourier transform infrared spectrophotometer (FTIR) and nuclear magnetic resonance (NMR). The thermosensitive-transparency measurement and swelling experiment show that the hydrophobic-modified PVA solutions and corresponding hydrogels exhibited thermosensitive phase transition behaviors with lower critical solution temperature (LCST) and UCST. The results indicated that the temperature-induced phase transition behavior of CHPVA hydrogels leads to their retarding swelling property and great potential as an efficient water plugging agent with excellent temperature and salt resistance. Full article

Thermosensitive chitosan/collagen hydrogels are osteoconductive and injectable materials. In this study, we aimed to improve these properties by adjusting the ratio of nanohydroxyapatite particles to calcium carbonate microcapsules in a β-glycerophosphate-crosslinked chitosan/collagen hydrogel. Two hydrogel systems with 2% and 5% nanohydroxyapatite particles were studied, each of which had varying microcapsule content (i.e., 0%, 1%, 2%, and 5%). Quercetin-incorporated calcium carbonate microcapsules were prepared. Calcium carbonate microcapsules and nanohydroxyapatite particles were then added to the hydrogel according to the composition of the studied system. The properties of the hydrogels, including cytotoxicity and biocompatibility, were investigated in mice. The calcium carbonate microcapsules were 2–6 µm in size, spherical, with rough and nanoporous surfaces, and thus exhibited a burst release of impregnated quercetin. The 5% nanohydroxyapatite system is a solid particulate gel that supports homogeneous distribution of microcapsules in the three-dimensional matrix of the hydrogels. Calcium carbonate microcapsules increased the mechanical and physical strength, viscoelasticity, and physical stability of the nanohydroxyapatite hydrogels while decreasing their porosity, swelling, and degradation rates. The calcium carbonate microcapsules–nanohydroxyapatite hydrogels were noncytotoxic and biocompatible. The properties of the hydrogel can be tailored by adjusting the ratio of calcium carbonate microcapsules to the nanohydroxyapatite particles. The 1% calcium carbonate microcapsules containing 5% nanohydroxyapatite particle–chitosan/collagen hydrogel exhibited mechanical and physical strength, permeability, and prolonged release profiles of quercetin, which were superior to those of the other studied systems and were optimal for promoting bone regeneration and delivering natural flavonoids. Full article