Thermoresponsive Gel Research Articles

Lidocaine-Loaded Thermoresponsive Gel for Accelerated Wound Healing in Dry Socket and Oral Wounds

Lidocaine-Loaded Thermoresponsive Gel for Accelerated Wound Healing in Dry Socket and Oral Wounds

3D-printed porous titanium rods equipped with vancomycin-loaded hydrogels and polycaprolactone membranes for intelligent antibacterial drug release

Implant-related infections pose significant challenges to orthopedic surgeries due to the high risk of severe complications. The widespread use of bioactive prostheses in joint replacements, featuring roughened surfaces and tight integration with the bone marrow cavity, has facilitated bacterial proliferation and complicated treatment. Developing antibacterial coatings for orthopedic implants has been a key research focus in recent years to address this critical issue. Researchers have designed coatings using various materials and antibacterial strategies. In this study, we fabricated 3D-printed porous titanium rods, incorporated vancomycin-loaded mPEG750-b-PCL2500 gel, and coated them with a PCL layer. We then evaluated the antibacterial efficacy through both in vitro and in vivo experiments. Our coating passively inhibits bacterial biofilm formation and actively controls antibiotic release in response to bacterial growth, providing a practical solution for proactive and sustained infection control. This study utilized 3D printing technology to produce porous titanium rod implants simulating bioactive joint prostheses. The porous structure of the titanium rods was used to load a thermoresponsive gel, mPEG750-b-PCL2500 (PEG: polyethylene glycol; PCL: polycaprolactone), serving as a novel drug delivery system carrying vancomycin for controlled antibiotic release. The assembly was then covered with a PCL membrane that inhibits bacterial biofilm formation early in infection and degrades when exposed to lipase solutions, mimicking enzymatic activity during bacterial infections. This setup provides infection-responsive protection and promotes drug release. We investigated the coating’s controlled release, antibacterial capability, and biocompatibility through in vitro experiments. We established a Staphylococcus aureus infection model in rabbits, implanting titanium rods in the femoral medullary cavity. We evaluated the efficacy and safety of the composite coating in preventing implant-related infections using imaging, hematology, and pathology. In vitro experiments demonstrated that the PCL membrane stably protects encapsulated vancomycin during PBS immersion. The PCL membrane rapidly degraded at a lipase concentration of 0.2 mg/mL. The mPEG750-b-PCL2500 gel ensured stable and sustained vancomycin release, inhibiting bacterial growth. We investigated the antibacterial effect of the 3D-printed titanium material, coated with PCL and loaded with mPEG750-b-PCL2500 hydrogel, using a rabbit Staphylococcus aureus infection model. Imaging, hematology, and histopathology confirmed that our composite antibacterial coating exhibited excellent antibacterial effects and infection prevention, with good safety in trials. Our results indicate that the composite antibacterial coating effectively protects vancomycin in the hydrogel from premature release in the absence of bacterial infection. The outer PCL membrane inhibits bacterial growth and prevents biofilm formation. Upon contact with bacterial lipase, the PCL membrane rapidly degrades, releasing vancomycin for antibacterial action. The mPEG750-b-PCL2500 gel provides stable and sustained vancomycin release, prolonging its antibacterial effects. Our composite antibacterial coating demonstrates promising potential for clinical application.

Development of Transdermal Formulation Integrating Polymer-Based Solid Microneedles and Thermoresponsive Gel Fucoidan for Antiaging: Proof of Concept Study.

Skin can be damaged by intense and prolonged exposure to ultraviolet (UV) radiation. Photoaging and acute damage from sun exposure result in collagen degradation and enzymatic activity decline in the skin. Fucoidan (FUC) exhibits potential antiaging properties, including collagen synthesis promotion and enzyme activity inhibition. However, FUC's limited ability to penetrate the skin layers due to its large molecular weight makes it a challenge for topical application. In this study, we successfully developed a new approach by integrating thermoresponsive gel (TRG) containing FUC with solid microneedles (SMNs) as a delivery system. TRG is formulated using a combination of Pluronic F127 (PF127) and Pluronic F68 (PF68) polymers, while SMNs are made from a mixture of poly(vinyl alcohol) (PVA) and poly(vinylpyrrolidone) (PVP) polymers with a variety of cross-linkers. Based on the results of ex vivo testing, it was shown that more than 80% of FUC can be delivered using the optimized formula. Furthermore, the results of the in vitro blood hemolytic test showed that TRG-FUC-SMNs were relatively biocompatible. In vivo antiaging activity tests using a rat model exposed to UV for 14 days showed that histological assessment, skin elasticity measurement, wrinkle evaluation, and skin moisture content had no significant differences (p < 0.05) compared to the positive control group. In contrast, a significant difference (p < 0.05) was observed when comparing the TRG-FUC-SMNs group with the group that received only TRG-FUC without pretreatment and negative controls. These findings suggest that FUC has potential to be delivered using the TRG system in combination with SMNs to harness its antiaging properties.

On-demand Opto-Laser activatable nanoSilver ThermoGel for treatment of full-thickness diabetic wound in a mouse model

Patients suffering from diabetes mellitus are prone to develop diabetic wounds that are non-treatable with conventional therapies. Hence, there is an urgent need of hour to develop the therapy that will overcome the lacunas of conventional therapies. This investigation reports the Quality by Design-guided one-pot green synthesis of unique Opto-Laser activatable nanoSilver ThermoGel (OL→nSil-ThermoGel) for hyperthermia-assisted treatment of full-thickness diabetic wounds in mice models. The characterization findings confirmed the formation of spherical-shaped nanometric Opto-Laser activatable nanoSilver (30.75 ± 2.7 nm; ∆T: 37 ± 0.2 °C → 66.2 ± 0.1 °C; at 1.8 W/cm2 NIR laser density). The findings indicated acceptable in vitro cytocompatibility and significant keratinocyte migration (95.04 ± 0.07 %) activity of OL→nSil towards HaCaT cells. The rheological data of OL→nSil hybridized in situ thermoresponsive gel (OL→nSil-ThermoGel) showed the gelling temperature at 32 ± 2 °C. In vivo studies on full-thickness diabetic wounds in a Mouse model showed OL→nSil-ThermoGel accelerated wound closure (94.42 ± 1.03 %) and increased collagen synthesis, angiogenesis, and decreased inflammatory markers. Similarly, immunohistochemistry study showed significant angiogenesis and faster phenotypic switching of fibroblasts to myofibroblasts in OL→nSil-ThermoGel treated diabetic wounds. Histological evaluation revealed a marked rise in keratinocyte migration, organized collagen deposition, and early regeneration of the epithelial layer compared to the diabetic wound control. In conclusion, the OL→nSil-ThermoGel modulates the cytokines, re-epithelialization, protein expression, and growth factors, thereby improving the repair and regeneration of diabetic wounds in mice.

Enhancement of skin localization of β-carotene from red fruit (Pandanus conoideus Lam.) using solid dispersion-thermoresponsive gel delivered via polymeric solid microneedles

Red fruit (Pandanus conoideus Lam.) boasts high β-carotene (BC) content, often consumed orally. However, absorption issues and low bioavailability due to food matrix interaction have led to transdermal delivery exploration. Nevertheless, BC has a short skin retention time. To address these limitations, this study formulates a β-carotene solid dispersion (SD-BC) loaded thermoresponsive gel combined with polymeric solid microneedles (PSM) to enhance in vivo skin bioavailability. Characterization of SD-BC includes saturation solubility, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and in vitro release. Characterization of SD-BC thermoresponsive gel includes gelation temperature, viscosity, rheological behaviour, pH, bio-adhesiveness, spreadability, and extrudability. PSM’s mechanical properties and insertion capability were assessed. Ex vivo and in vivo dermato-pharmacokinetic studies, drug content, hemolysis, and skin irritation assessments were conducted to evaluate overall performance. Results confirm amorphous SD-BC formation, enhancing solubility. Both SD-BC thermoresponsive gel and PSM exhibit favourable characteristics, including rheological properties and mechanical strength. In vitro release studies showed a seven-fold increase in BC release compared to plain hydrogel. SD-BC thermoresponsive gel combined with PSM achieves superior ex vivo permeation (Cmax = 305.43 ± 32.07 µg.mL−1) and enhances in vivo dermato-pharmacokinetic parameters by 200–400 %. Drug content, hemolysis, and skin irritation studies confirmed its safety and non-toxicity.

Thermoresponsive gel containing bilirubin nanoparticles exerts anti-inflammatory effects by inhibiting neutrophil infiltration and augmenting interleukin-10 levels in carrageenan-induced rat paw edema.

Topical corticosteroids treat cutaneous inflammation but have side effects. In earlier studies, bilirubin exhibited anti-inflammatory effect, but its hydrophobicity and poor absorption limit its potential. Synthesis of bilirubin nanoparticles (BNP) and bilirubin nanoparticles gels (BNP gel) to study the anti-inflammatory effect of topical BNP gel against carrageenan-induced rat paw edema in Wistar rats. BNP were synthesized, and BNP gels were prepared by mixing BNP of different concentrations with pluronic F-127 (PF-127). A different group for each formulation was assigned with five rats in each group. After 1 h of carrageenan (1% [w/v]) injection in each group, different gels were applied topically to their respective groups. Paw edema size, percent inflammation, percent edema inhibition, and inhibition time50 were evaluated. Interleukin-10 (IL-10) levels and neutrophil infiltration in rat paw tissue were evaluated by enzyme-linked immunosorbent assay and hematoxylin and eosin, respectively. Synthesized spherical-shaped BNP had negative zeta potential. BNP gels markedly reduced paw edema size and % inflammation as compared to carrageenan and bulk bilirubin gel (Bulk B gel) treated group and significantly increased IL-10 levels and inhibited neutrophil infiltration. BNP gels exhibited a better anti-inflammatory effect than bulk B gel and comparable anti-inflammatory potential with clobetasol.

Thermo-responsive selective recovery of protonated dyes by carbon-doped boron nitride-(N-isopropylacrylamide) composite gel

Approximately 280,000 tons of textile dyes are discharged into water bodies annually worldwide, which have the potential to be transformed into resources through selective recovering them from the effluents. Herein, a series of thermo-responsive carbon-doped boron nitride composite gels (TBCN) have been successfully synthesized, with optimum mass ratio BCN:NIPAM = 0.2:1 and pH 7. SEM-EDX, FTIR, XPS and theoretical calculation support that carbon-doped boron nitride (BCN) was uniformly dispersed inside the N-isopropylacrylamide (NIPAM) matrix through van der Waals interaction and hydrogen bonding. TBCN samples selectively recover protonated dyes from binary dyes solution through adjusting temperature instead of pH, which reduce the secondary pollution of acidic wastewater and are easier to recycle than powder adsorption materials. The removal rates of neutral red (NR)and malachite green (MG)by TBCN-2 reach 98.80 % and 98.40 %, which are obviously higher than methyl orange (MO: 42.48 %) and methylene blue (MB: 44.27 %). Through rising the temperature to 40 ℃, the adsorbed NR and MG are released, and the recovery rates are 78.50 % and 77.32 %, whereas those of MO and MB are only 26.05 % and 24.53 %. Furthermore, NR (or MG) can be selectively recovered from the mixed solution of NR-MB and NR-MO (or MG-MB and MG-MO) by TBCN-2, with the maximum removal rate of 93.51 %. For cycle stability, TBCN-2 can be used repeatedly at least four times with recovery rate＞58.80 %. TBCN-2 is an eco-friendly material and has good application prospect in dye resource utilization.

Thermoresponsive Gels with Embedded Starch Microspheres for Optimized Antibacterial and Hemostatic Properties.

Apart from single hemostasis, antibacterial and other functionalities are also desirable for hemostatic materials to meet clinical needs. Cationic materials have attracted great interest for antibacterial/hemostatic applications, and it is still desirable to explore rational structure design to address the challenges in balanced hemostatic/antibacterial/biocompatible properties. In this work, a series of cationic microspheres (QMS) were prepared by the facile surface modification of microporous starch microspheres with a cationic tannic acid derivate, the coating contents of which were adopted for the first optimization of surface structure and property. Thermoresponsive gels with embedded QMS (F-QMS) were further prepared by mixing a neutral thermosensitive polymer and QMS for second structure/function optimization through different QMS and loading contents. In vitro and in vivo results confirmed that the coating content plays a crucial role in the hemostatic/antibacterial/biocompatible properties of QMS, but varied coating contents of QMS only lead to a classical imperfect performance of cationic materials. Inspiringly, the F-QMS-4 gel with an optimal loading content of QMS4 (with the highest coating content) achieved a superior balanced in vitro hemostatic/antibacterial/biocompatible properties, the mechanism of which was revealed as the second regulation of cell-material/protein-material interactions. Moreover, the optimal F-QMS-4 gel exhibited a high hemostatic performance in a femoral artery injury model accompanied by the easy on-demand removal for wound healing endowed by the thermoresponsive transformation. The present work offers a promising approach for the rational design and facile preparation of cationic materials with balanced hemostatic/antibacterial/biocompatible properties.

Synthesis of thermo-responsive polymer gels composed of star-shaped block copolymers by copper-catalyzed living radical polymerization and click reaction

ABSTRACT In recent times, there has been a significant surge in research interest surrounding thermo-responsive water-soluble polyacrylamides, primarily due to their intriguing capability to undergo significant solubility changes in water. These polymers exhibit the remarkable ability to shift from a soluble to an insoluble state in response to temperature variations. The capacity of these polymers to dynamically respond to temperature changes opens up exciting avenues for designing smart materials with tunable properties, amplifying their utility across a spectrum of scientific and technological applications. Researchers have been particularly captivated by the potential applications of thermo-responsive water-soluble polyacrylamides in diverse fields such as drug delivery, gene carriers, tissue engineering, sensors, catalysis, and chromatography separation. This study reports the construction and functionalization of polymer gels consisting of a polymer network of polyacrylamide derivatives with nano-sized structural units. Specifically, thermo-responsive polymer gels were synthesized by combining well-defined star-shaped polymers composed of polyacrylamide derivatives with a multifunctional initiator and linking method through a self-accelerating click reaction. The polymerization system employed a highly living approach, resulting in polymer chains characterized by narrow molecular weight distributions. The method’s high functionality facilitated the synthesis of a temperature-responsive block copolymer gel composed of N-isopropyl acrylamide (NIPA) and N-ethyl acrylamide (NEAA). The resulting polymer gel, comprising star-shaped block copolymers of NIPA and NEAA, showcases smooth volume changes with temperature jumps.

L-arginine–phosphatidylcholine thermoresponsive gel for enhanced transdermal delivery and L-929 cell cytotoxicity evaluation

The vasodilator effect of the semi-essential amino acid, L-arginine (LA) is crucial in the clinical management of angina pain and erectile dysfunction. Moreover, the limited bioavailability and the drug’s polar nature navigate the development of new formulation strategies for effective transdermal delivery, especially for the penile route. Thus, herein, we prepared the L-arginine–phosphatidylcholine (LA–PC) complex by solvent evaporation technique and converted it into a thermoresponsive gel (LA–PC gel). The optimized complex was selected for the preparation of gel using poloxamer 407, lactic acid, and purified water. Simultaneously we prepared the LA thermoresponsive gel (LA gel). The gels were characterized for their appearance, particle size, pH, osmolality, spreadability, SEM, FTIR, viscosity, TEM, viscoelastic properties, and skin permeability using the Strat-M® membrane at low pH for effective and safe penile and vaginal delivery. We observed that the LA–PC gel showed the smallest droplet size (<100 nm), a zeta potential of −59 mV indicates its stability with good viscoelastic behavior. The in vitro skin permeation reveals that; at 15 min, the permeation of LA for LA–PC gel, was 33.20% with a flux of 2.19 mg/cm2/min, and in the case of LA gel, the permeation of LA was only 18% at 45 minutes with a flux of 1.02 mg/cm2/min. The in vitro cytocompatibility was conducted using an L-929 cell line, and we found that both gels were nontoxic up to 100 µg/mL concentration. In summary, LA–PC gel could have a significant impact on the quick and sustained release, compared to LA gel.

Control of phase transition temperature of thermoresponsive poly(ionic liquid) gels and application to a water purification system using these gels with polydopamine

Demand for purified water is increasing as the population grows. Water purification systems combining thermoresponsive materials and adsorbents that can be used in areas without electricity or other energy infrastructure have begun to be reported. The thermoresponsive hydrogel used in this system must be able to adsorb and desorb a large amount of water, react drastically to temperature, and have a phase transition temperature that can be easily changed depending on the environment in which it is used. In this study, thermoresponsive ionic liquid-derived polyelectrolyte gels (poly(IL) gels) were prepared as lower critical solution temperature (LCST)-type thermoresponsive materials. As a result, poly(IL) gel, which exhibits drastic swelling/shrinking and reversible adsorption/desorption of a large amount of water (44 times the amount of water to its own weight), was successfully fabricated. The phase transition temperature can be controlled between 20 °C and 35 °C by copolymerizing ILs with different structures. Then, polydopamine (PDA), which can serve as a photothermal conversion material as well as an adsorbent for contaminants, was polymerized on the surface of the poly(IL) gel. In addition to its role as an adsorbent, PDA can also serve as a photothermal conversion material. First, a poly(IL)-based material with PDA is swollen in contaminated water. Subsequent irradiation with sunlight induces an LCST-type phase transition behavior by converting light energy into heat. Finally, the contaminants remain adsorbed, and only the water is discharged from the material to obtain purified water. Using this material, we were able to show that organic dyes are removed from aqueous solutions with high efficiency using sunlight.

Thermoresponsive oil-continuous gels based on double-interpenetrating colloidal-particle networks.

Gels composed of multicomponent building blocks offer promising opportunities for the development of novel soft materials with unique and useful structures. While interpenetrating polymer networks have been extensively studied and applied in the creation of these gels, equivalent strategies utilizing colloidal particles have received limited scientific and technological attention. This study presents a novel class of thermo-responsive apolar double gels from interpenetrating networks of attractive colloidal silica and lipid particles. These double gels are easily assembled and suitable for the fabrication of 3D-printed edible soft constructs. Emphasis is focused on the rheological properties and structure emerging on the dilute regime (ϕ ≲ 0.1). Rheological investigations demonstrate that double gels exhibit greater stiffness and resilience to yielding compared to their single lipid gel counterparts. The scaling behavior of the oscillatory linear shear moduli and the critical strain for yielding with volume fraction remain comparable between single and double gels. Creep yielding in double gels exhibits two exponential decay regimes, suggesting the presence of thicker gel strands undergoing flow. Visualization and quantification of the quiescent microstructure confirms the existence of such denser aggregates devoid of larger clusters due to steric hindrance of interpenetrating networks in double gels. This is in stark contrast to lipid single gels where aggregates grow unrestrictedly into larger clusters. Our study constitutes the first demonstration on the assembly of apolar double gel networks as a promising avenue for the design of novel soft materials and foods with tailored structure and mechanics.

Preparation and characterization of a nanohydroxyapatite and sodium fluoride loaded chitosan-based in situ forming gel for enamel biomineralization

The development of remineralizing smart biomaterials is a contemporary approach to caries prevention. The present study aimed at formulation preparation and characterization of a thermoresponsive oral gel based on poloxamer and chitosan loaded with sodium fluoride (NaF) and nanohydroxyapatite (nHA) to treat demineralization. The chemical structure and morphology of the formulation were characterized using FTIR and FESEM-EDS tests. Hydrogel texture, rheology, and stability were also examined. The hydrogel was in a sol state at room temperature and became gel after being placed at 37 °C with no significance different in gelation time with the formulation without nHA and NaF as observed by t-test. The FTIR spectrum of nHA/NaF/chitosan-based hydrogel indicated the formation of physical crosslinking without any chemical interactions between the hydrogel components. The FESEM-EDS results demonstrated the uniform distribution of each element within the hydrogel matrix, confirming the successful incorporation of nHA and NaF in the prepared gel. The hardness, hydrogel’s adhesiveness, and cohesiveness were 0.9 mJ, 1.7 mJ, and 0.37, respectively, indicating gel stability and the acceptable retention time of hydrogels. The formulation exhibited a non-Newtonian shear-thinning pseudoplastic and thixotropic behavior with absolute physical stability. Within the limitation of in vitro studies, nHA/NaF/chitosan-based in situ forming gel demonstrated favorable properties, which could be trasnsorm into a gel state in oral cavity due to poloxamer and chitosan and can prevent dental caries due to nHA and NaF. We propose this formulation as a promising dental material in tooth surface remineralization.

Controlled Release of Mesenchymal Stem Cell-Conditioned Media from a Microsphere/Gel-Based Drug Delivery System for Wound Healing of Tympanic Membrane Perforations

Chronic tympanic membrane (TM) perforation increases patient susceptibility to infection, hearing loss, and other side effects. Current clinical treatment, surgical grafting, can result in detrimental side effects including nerve damage, dizziness, or hearing loss. Therefore, it is essential to develop novel therapeutic procedures that can induce or accelerate healing in minimally or noninvasive approaches. Cell-free therapies have safety advantages over stem cells and are logistically favorable for clinical use. The regenerative potential by mesenchymal stem cell-conditioned media (CM) has been promising. In this study, poly(lactic-co-glycolic acid) (PLGA) microspheres with CM encapsulated have been developed as a cell-free alternative regenerative treatment for TM perforation. The results suggest that the PLGA microspheres were capable of encapsulating and releasing CM for up to 21 days. The in vitro scratch wound proliferation assays showed increased wound healing ability of CM-loaded microspheres. In vivo guinea pig models treated with CM drops and CM-loaded microspheres using a thermoresponsive gel carrier demonstrated potential for wound healing in TM perforation. These studies provide a basis for further examination of the delivery of stem cell CM and investigation of time-dependent wound healing, long-term ototoxicity, and hearing restoration.

Review of the Perspectives and Study of Thermo-Responsive Polymer Gels and Applications in Oil-Based Drilling Fluids.

Thermoresponsive polymer gels are a type of intelligent material that can react to changes in temperature. These materials possess excellent innovative properties and find use in various fields. This paper systematically analyzes the methods for testing and regulating phase transition temperatures of thermo-responsive polymer gels based on their response mechanism. The report thoroughly introduces the latest research on thermo-responsive polymer gels in oil and gas extraction, discussing their advantages and challenges across various environments. Additionally, it elucidates how the application limitations of high-temperature and high-salt conditions can be resolved through process optimization and material innovation, ultimately broadening the scope of application of thermo-responsive polymer gels in oil and gas extraction. The article discusses the technological development and potential applications of thermo-responsive polymer gels in oil-based drilling fluids. This analysis aims to offer researchers in the oil and gas industry detailed insights into future possibilities for thermo-responsive polymer gels and to provide helpful guidance for their practical use in oil-based drilling fluids.

Tuning Blood-Material Interactions to Generate Versatile Hemostatic Powders and Gels.

Polymer-based hemostatic materials/devices have been increasingly exploited for versatile clinical scenarios, while there is an urgent needto reveal the rational design/facile approach for procoagulant surfaces through regulating blood-material interactions. In this work, degradable powders (PLPS) and thermoresponsive gels (F127-PLPS) are readily developed as promising hemostatic materials for versatile clinical applications, through tuning blood-material interactions with optimized grafting of cationic polylysine: the former is facilely prepared by conjugating polylysine onto porous starch particle, while F127-PLPS is prepared by the simple mixture of PLPS and commercial thermosensitive polymer. In vitro and in vivo results demonstrate that PLPS2 with the optimal-/medium content of polylysine grafts achieve the superior hemostatic performance. The underlying procoagulant mechanism of PLPS2 surface is revealed as the selective fibrinogen adsorption among the competitive plasma-protein-adsorption process, which is the foundation of other blood-material interactions. Moreover, in vitro results confirm the achieved procoagulant surface of F127-PLPS through optimal PLPS2 loading. Together with the tunable thermoresponsiveness, F127-PLPS exhibits outstanding hemostatic utilization in both femoral-artery-injury and renal-artery-embolization models. The work thereby pioneers an appealing approach for generating versatile polymer-based hemostatic materials/devices.

Fenofibrate loaded nanofibers based thermo-responsive gel for ocular delivery: Formulation development, characterization and in vitro toxicity study

Fenofibrate loaded nanofibers based thermo-responsive gel for ocular delivery: Formulation development, characterization and in vitro toxicity study

Micro array patch assisted transdermal delivery of high dose, ibuprofen sodium using thermoresponsive sodium alginate/poly (vinylcaprolactam) in situ gels depot

Current study reports the combined technique of microneedle array patches and thermoresponsive gels. Microneedles array patch mediated insitu skin depots were evaluated for sustain drug delivery using sodium alginate/Poly (vinylcaprolactam) thermoresponsive gels. Their phase transition property from sol-gel state was monitored with AR2000 rheometer. Ibuprofen sodium was loaded in optimized formulations. The non-soluble cross-linked microneedle array patches (MAPs) were prepared from variable biocompatible polymers using silicone micromoulds. The fabricated MAPs were evaluated for mechanical stability, inskin dissolution, insertion forces and moisture contents. The penetration depth of MAPs in neonatal rabbit skin was tracked by optical coherence tomography. The optimized MAPs (GP10000) were used as microporation source in skin owing to their stable nature. Pores formation in skin samples after MAPs treatment was confirmed by optical coherence tomography, dye binding and skin integrity analysis. The invitro permeation of Ibuprofen sodium from formulations was studied using Franz cells across intact skin and MAPs applied skin. It was concluded from the results that Ibuprofen sodium permeation was observed for longer time through MAPs treated skin as compared to intact skin. Confocal study confirmed the diffusion of drug loaded formulations in deeper tissues with higher intensity.

Rivastigmine-DHA ion-pair complex improved loading in hybrid nanoparticles for better amyloid inhibition and nose-to-brain targeting in Alzheimer’s

Rivastigmine hydrogen tartrate (RIV-HT) is given orally for Alzheimer's disease. However, oral therapy shows low brain bioavailability, short half-life and gastrointestinal-mediated adverse effects. RIV-HT intranasal delivery can avoid these side effects, but its low brain bioavailability remains challenging. These issues could be solved with hybrid lipid nanoparticles with enough drug loading to enhance RIV-HT brain bioavailability while avoiding oral route side effects. The RIV-HT and docosahexaenoic acid (DHA) ion-pair complex (RIV:DHA) was prepared to improve drug loading into lipid-polymer hybrid (LPH) nanoparticles. Two types of LPH, i.e., cationic (RIV:DHA LPH(+ve)) and anionic LPH (RIV:DHA LPH(-ve)) were developed. The effect of LPH surface charge on in-vitro amyloid inhibition, in-vivo brain concentrations and nose-to-brain drug targeting efficiency were investigated. LPH nanoparticles showed concentration dependant amyloid inhibition. RIV:DHA LPH(+ve) demonstrated relatively enhanced Aβ1-42 peptide inhibition. The thermoresponsive gel embedded with LPH nanoparticles improved nasal drug retention. LPH nanoparticles gel significantly improved pharmacokinetic parameters compared to RIV-HT gel. RIV:DHA LPH(+ve) gel showed better brain concentrations than RIV:DHA LPH(-ve) gel. The histological examination of nasal mucosa treated with LPH nanoparticles gel showed that the delivery system was safe. In conclusion, the LPH nanoparticle gel was safe and efficient in improving the nose-to-brain targeting of RIV, which can potentially be utilized in managing Alzheimer's.

Thermoresponsive mucoadhesive hydrogel based on Pluronic F127/thiolated glycol chitosan for intravesical administration of celecoxib/gemcitabine

In recent years, mucoadhesivein situ gelling formulations for intravesical application have been studied to improve the therapeutic outcomes of bladder cancer patients. Here, we carefully tuned a Pluronic F127-based thermoresponsive gel using two mucoadhesive thiolated derivatives of glycol chitosan, S-preactivated N-acetylcysteine (NAC)- and glutathione (GSH)-glycol chitosan (GC). The gel was loaded with a combination of Gemcitabine (GEM) and Celecoxib (CEX), and the aqueous solubility of the latter was increased for a synergic influence between Pluronic and the inclusion complex of 2-Hydroxypropyl-β-cyclodextrin/CEX. The effect of the inclusion complex of two mucoadhesive polymers on rheological features of Pluronic based gels was highlighted to select the best performance. Finally, ex-vivo retention studies, mucosal penetration and in-vitro drug release of the selected systems were monitored for 24 h, providing enhanced retention properties (50% after 6 h) and continued drug release.