Thermoreversible Gels Research Articles

Thermo-Reversible Hybrid Gels Formed from the Combination of Isotactic Polystyrene and [Fe(II) (4-Octadecyl-1,2,4-Triazole)3(ClO4)2]n Metallo-Organic Polymer: Thermal and Viscoelastic Properties.

Nano-sized one-dimensional metallo-organic polymers, characterized by the phenomenon of spin transition, are excellent candidates for advanced technological applications such as optical sensors, storage, and information processing devices. However, the main drawback of this type of polymers is their fragile mechanical properties, which hinders its processing and handling, and makes their practical use unfeasible. To overcome this problem, in this work, hybrid thermo-reversible gels are synthesized by combination of a metallo-organic polymer and isotactic polystyrene (iPS) in cis-decaline. A detailed investigation of the thermal and viscoelastic properties of the hybrid gels, in terms of iPS and metallo-organic polymer concentration is performed by means of differential scanning calorimetry and oscillatory rheology, respectively. From the analysis of the thermal properties, three transitions have been determined upon heating: Monotectic transition of the iPS gel, melting of the iPS gel, and melting of the metal-organic polymer gel, which suggest that the gels of the two polymers are formed independently in the hybrid gel, as long as the two polymers are in concentrations above the corresponding critical gelation concentrations. Results regarding viscoelastic properties and morphology confirmed that hybrid gels consisted of an interpenetrated network of polymer gels, formed by iPS and metallo-organic poymer gels growing independently.

Thermoreversible gelation with ion-binding cross-links of variable multiplicity.

Thermoreversible gelation and liquid-liquid phase separation are theoretically studied for the gels of polyfunctional molecules (polymers) whose network junctions are formed by complexation of functional groups on the polymer chains with added metal ions. Phase diagrams on the polymer/ion/solvent concentration plane, including both sol-gel transition lines and liquid-liquid phase separation lines (spinodals), are derived as functions of the polymer functionality, molecular weight, maximum coordination number of ions, and temperature. Binding isotherms of ions are also calculated as functions of the ion concentration. Results of the calculated sol-gel transition lines are compared with our recent experimental data on gelation of star block and telechelic, acrylic copolymers cross-linked by iron ions. It is shown that, owing to reaction stoichiometry, there is an optimal ion concentration at which the solution gels for the lowest polymer concentration and also that a re-entrant sol phase appears in the ion concentrations higher than the optimal one. The effect of stepwise complex formation constants on the re-entrant phase is studied in detail.

Chlorpheniramine maleate containing chitosan-based nanoparticle-loaded thermosensitive in situ gel for management in allergic rhinitis.

The aim of the present study was to fabricate a thermosensitive gel containing chlorpheniramine maleate (CPM)-loaded nanoparticles following intranasal administration for effective treatment of allergic rhinitis. Chitosan-based nanoparticles were prepared by a precipitation method followed by the addition of developed NPs within the poloxamer 407- and carbopol 934P-based mucoadhesive thermoreversible gel. Developed formulations were evaluated for particle size, PDI, % entrapment efficiency, and % cumulative drug permeation. NP3 formulation was found to be optimized on the basis of minimum particle size (143.9nm), maximum entrapment efficiency (80.10 ± 0.414%), and highest drug permeation (90.92 ± 0.531%). The optimized formulation NP3 was then formulated into thermoreversible in situ gel. This intensifies the contact between the nasal mucosa and the drug and increases and facilitates the drug absorption which results in increased bioavailability. G4 formulation was selected as the optimized formulation on the basis of gelation ability and mucoadhesive strength. Histology was carried out to examine the damage caused by the optimized G4 formulation. Results revealed no visual signs of tissue damage thus indicated safe nasal delivery of nanoparticulate in situ gel formulation G4. Thus, intranasal CPM NP-loaded in situ gel was found to be a promising formulation for the management of allergic rhinitis.

Combinatorial Therapeutic Drug Delivery of Riboflavin and Olopetadine for the Treatment of Keratoconus Affected Corneas of Mice

The present study deals with the development and evaluation of novel thermoreversible gel containing Riboflavin and Olopatadine for the treatment of Keratoconus. The novel gel was prepared by using polymers like Poloxamer and hydroxypropyl methyl cellulose (HPMC) using cold method. The formulated system was evaluated for clarity, appearance, pH, gelling temperature, ex vivo diffusion study, Isotonicity, hemolytic study and effect in keratoconus affected mice model. The results showed that formulated gel was found to be clear and transparent having high gelling capacity. The pH was found between 6.5 to 6.9 and gelation temperature between 34 to 37 °C. All formulations were found isotonic and the hemolytic study performed proved the non-hemolytic nature of formulation. Drug content was also within acceptable limit. The F5 formulation was found to be optimized considering all evaluation parameters. F5 formulation showed maximum amount of release (98.5 and 99.6% for Ribo and Olo respectively) within 8 hrs as compare to other formulations. The effect of formulation on keratoconus affected mice showed that matrix can be produced after stimulation of KC cells and the increased thickness can be result of increase number of cells or matrix produced per cell. These results clearly conclude the potential of combinatorial therapeutic drug delivery of riboflavin and olopetadine for the treatment of keratoconus affected corneas of mice.

Nose-to-brain delivery of levetiracetam after intranasal administration to mice

Despite being one of the most commonly prescribed antiepileptic drugs, levetiracetam is marketed in oral and intravenous dosage forms, which are associated to drug-drug interactions and drug-resistant epilepsy (DRE). The purpose of the present study was to assess the potential of the intranasal route to deliver levetiracetam into the brain, due to the particular anatomical features of the nasal cavity. After development and characterization of the drug formulation, a thermoreversible gel loaded with levetiracetam was administered to CD-1 male mice by intranasal route and its pharmacokinetics compared to those observed after intravenous administration. Similar plasma pharmacokinetic profiles were obtained and the intranasal absolute bioavailability was 107.44%, underscoring that a high drug fraction was systemically absorbed. In brain tissue, maximum drug concentrations were 4.48 and 4.02 μg/g (intranasal vs intravenous) and the mean cerebral concentrations were significantly higher after intranasal administration. The percentage of drug targeting efficiency was 182.35% while direct transport percentage was 46.38%, suggesting that almost 50% of levetiracetam undergoes direct nose-to-brain delivery. Complementarily, an in vivo intranasal repeated dose toxicity study was performed and no relevant histopathological alterations were observed. The herein proposed non-invasive and safe intranasal administration route allowed a direct nose-to-brain delivery of levetiracetam and is a promising strategy for the treatment of DRE.

Enhancement of the Textural and Gel Properties of Frankfurters by Adding Thermo-reversible or Thermo-irreversible Curdlan Gels.

The influence of different addition levels (0.1% to 0.5%) of thermo-reversible curdlan gels (TRC) and thermo-irreversible curdlan gels (TIRC) on the physicochemical and textural characteristics of frankfurters, as well as dynamic rheological properties of meat batters, was investigated. Increased percentages of TRC and TIRC were associated with lower cooking loss and quicker relaxation times, as well as superior emulsion stability, and higher L* -values and b* -values of frankfurters (P < 0.05). Moreover, with equal curdlan concentrations from 0.3% to 0.5%, TRC showed higher hardness and chewiness values than those with added TIRC (P < 0.05), but the gumminess, springiness, and resilience values were almost the same between each treatment (P > 0.05). The textural profile results were in strong agreement with the rheological data. Principal component analysis revealed that certain quality attributes were affected differently by the inclusion levels of TRC and TIRC. Additionally, the distinctive mechanism of the formation of the complex meat protein network by TRC or TIRC was also clarified and verified via scanning electron microscopy analysis. Further studies will investigate the molecular interactions of meat proteins with these two types of curdlan gels as a function of addition levels. PRACTICAL APPLICATION: Curdlan can form two different types of gels mainly depending on heating temperature, designated as thermo-reversible curdlan gels (TRC) and thermo-irreversible curdlan gels (TIRC), respectively. The addition of these two gels could improve the textural and gel properties of frankfurters, as well as improve the rheological profiles of meat batters. Each gel type invokes a different mechanism of influence on the formation of the complex meat protein network. Results indicate that TRC (mainly as an effective gelling agent) and TIRC (mainly as a potential fat-mimetic) can provide distinctive frankfurter formulations catered to the requirements preferred by different consumers.

F FORMULATION DEVELOPMENT AND EVALUATION OF CARBOPOL-INCORPORATED THERMOREVERSIBLE GELS OF PSEUDOEPHEDRINE FOR RECTAL DRUG DELIVERY

Objectives: The present study describes the preparation and evaluation of a Poloxamer 188 (P188)-based thermoreversible gel using Carbopol 934P (C934P) as a mucoadhesive polymer of pseudoephedrine for enhancing the bioavailability and to avoid the first-pass metabolism.&#x0D; Materials and Methods: Five formulations (F1-F5) were prepared using cold method. The prepared gels were characterized by pH, drug content, spreadability, mucoadhesive force, gelation temperature, and drug release profile. Thermoreversibility of P188/C934P gel was demonstrated by rheological studies. The drug-polymer compatibility was studied using Fourier transform infrared (FTIR).&#x0D; Results: The incorporation of carbopol into P188 gel also reduced the amounts of drug released from the gel formulations. FT-IR studies revealed that there are no interactions between the drug and polymers. Drug content of gels was estimated and the results were found to be satisfactory. In vitro dissolution studies revealed a good drug release from the gels. The drug release was higher in formulations F4 and F5 and lower in F1, F2, and F3 formulations. The order of drug release was found to be F5&gt;F4&gt;F3&gt;F2&gt;F1.&#x0D; Conclusion: These findings suggested that developed thermoreversible gels could be used as promising dosage forms to rectal drug delivery for prolonged periods in the management of hemorrhoids.

Main features and applications of organogels in cosmetics.

Cosmetic treatments aim at improving skin appearance through vehicles of good sensory properties. Those vehicles are mainly emulsions and gels designed to deliver safe and effective compounds to skin. Creams and serums are widely used to achieve these goals, but recently a new type of formulation known as organogels triggered scientific attention, particularly in the design of both topical and cosmetic formulations. It has been established that the lipophilic nature of organogels makes it an excellent candidate for the delivery of cosmetic molecules through skin. In this review, we discuss the properties and characteristics of organogels and present the advantages of the application of these systems in cosmetics.

Increasing valence pushes DNA nanostar networks to the isostatic point

The classic picture of soft material mechanics is that of rubber elasticity, in which material modulus is related to the entropic elasticity of flexible polymeric linkers. The rubber model, however, largely ignores the role of valence (i.e., the number of network chains emanating from a junction). Recent work predicts that valence, and particularly the Maxwell isostatic point, plays a key role in determining the mechanics of semiflexible polymer networks. Here, we report a series of experiments confirming the prominent role of valence in determining the mechanics of a model system. The system is based on DNA nanostars (DNAns): multiarmed, self-assembled nanostructures that form thermoreversible equilibrium gels through base pair-controlled cross-linking. We measure the linear and nonlinear elastic properties of these gels as a function of DNAns arm number, f, and concentration [DNAns]. We find that, as f increases from three to six, the gel's high-frequency plateau modulus strongly increases, and its dependence on [DNAns] transitions from nonlinear to linear. Additionally, higher-valence gels exhibit less strain hardening, indicating that they have less configurational freedom. Minimal strain hardening and linear dependence of shear modulus on concentration at high f are consistent with predictions for isostatic systems. Evident strain hardening and nonlinear concentration dependence of shear modulus suggest that the low-f networks are subisostatic and have a transient, potentially fractal percolated structure. Overall, our observations indicate that network elasticity is sensitive both to entropic elasticity of network chains and to junction valence, with an apparent isostatic point [Formula: see text] in agreement with the Maxwell prediction.

Characterizing the yielding processes in pluronic-hyaluronic acid thermoreversible gelling systems using oscillatory rheology

Pluronic F-127 (Pl), a triblock copolymer that exhibits thermoreversible sol-gel transition, is being used with additives such as polysaccharides for enhanced gel stability and mechanical strength for controlled drug delivery applications. This study aims at elucidating the gelation behavior and structure-property relationship (at physiological temperature) of pluronic in the presence of hyaluronic acid (HA) using linear and nonlinear rheology. Small amplitude oscillatory shear of the gels indicated weak frequency dependence of G ′ and G ′ ′. Large amplitude oscillatory shear (LAOS) response indicated flow induced yielding with both the moduli following power law decay beyond the critical strain amplitude. Stress waveform analysis, Fourier analysis, and Chebyshev decomposition indicated similar qualitative features for gels with different HA content. Interestingly, there is a non-monotonic variation in the dynamic light scattering timescales, G ′ (linear regime), and the critical stress values (at corresponding critical strains) with HA content. The physical insights obtained were understood in terms of a cage picture of soft glassy materials. Relaxation times corresponding to yielding transition obtained from strain rate frequency superposition measurements showed similar qualitative variation as those obtained from elastoviscoplastic modeling of the yielding processes occurring during an LAOS cycle. Based on these analyses, we obtain quantitative description of nonlinear rheological response of the Pl-HA gels.Pluronic F-127 (Pl), a triblock copolymer that exhibits thermoreversible sol-gel transition, is being used with additives such as polysaccharides for enhanced gel stability and mechanical strength for controlled drug delivery applications. This study aims at elucidating the gelation behavior and structure-property relationship (at physiological temperature) of pluronic in the presence of hyaluronic acid (HA) using linear and nonlinear rheology. Small amplitude oscillatory shear of the gels indicated weak frequency dependence of G ′ and G ′ ′. Large amplitude oscillatory shear (LAOS) response indicated flow induced yielding with both the moduli following power law decay beyond the critical strain amplitude. Stress waveform analysis, Fourier analysis, and Chebyshev decomposition indicated similar qualitative features for gels with different HA content. Interestingly, there is a non-monotonic variation in the dynamic light scattering timescales, G ′ (linear regime), and the critical stress values...

Mechanical reinforcement of methylcellulose hydrogels by rigid particle additives

Methylcellulose hydrogels are attracting considerable interest due to their unique thermo-reversible gelation. The present work focuses on the attempt to tune, control and improve the mechanical response of these hydrogels by using silica (SiO2), alumina (Al2O3) and boron carbide (B4C) particles, while preserving their ability to thermo-gelate. A systematic experimental study reveals the dependence of the flow stress of the hydrogel-composite on the type and size of particle additive. Methylcellulose composite hydrogels also show increased flow-stress dependence on temperature, compared to the parent hydrogel. Similarly, some of these novel composite exhibit very high strain-rate sensitivity, with up to 90 times increase of strength in the dynamic regime. Thus, the present study offers simple tools to fine-tune the mechanical properties of these highly applicable methylcellulose hydrogels, by using small amounts of additives. Of the studied composites, the best results for dynamic flow-stress increase were achieved with nanometric boron carbide particles. This could be due to the large surface area for interaction with the methylcellulose and with the particles serving as heterogenic focal points for phase-transition.

Crystallization-Arrested Viscoelastic Phase Separation in Semiconducting Polymer Gels

Through a combination of rheological characterization and temperature-variable imaging methods, a novel gelation pathway in dilute solutions of a semiconducting polymer to achieve interconnected, crystalline networks with hierarchical porosity is reported. Upon rapid cooling, solutions of regioregular poly(3-hexylthiophene) (RR-P3HT) in ortho-dichlorobenzene formed thermoreversible gels. Temperature-variable confocal microscopy revealed cooling-induced structural rearrangement to progress through viscoelastic phase separation. The phase separation process arrested prematurely during the formation of micron-sized solvent-rich "holes" within the RR-P3HT matrix due to intrachain crystallization. Cryogen-based scanning electron microscopy of RR P3HT gels revealed the existence of an interfibrillar network exhibiting nano-sized pores. Remarkably, these networks formed to equal gel strengths when a third component, either small molecule phenyl C61 butyric acid methyl ester (PCBM) or non-crystallizing regiorandom (Rra)-P3HT, was added to the solution. Organic solar cells in which the active layers were deposited from phase-separated solutions displayed 45% higher efficiency compared to reference cells.

Antibacterial drug release from a biphasic gel system: Mathematical modelling

Bacterial infections represent an important drawback in the orthopaedic field, as they can develop either immediately after surgery procedures or after some years. Specifically, in case of implants, they are alleged to be troublesome as their elimination often compels a surgical removal of the infected implant. A possible solution strategy could involve a local coating of the implant by an antibacterial system, which requires to be easily applicable, biocompatible and able to provide the desired release kinetics for the selected antibacterial drug. Thus, this work focusses on a biphasic system made up by a thermo-reversible gel matrix (Poloxamer 407/water system) hosting a dispersed phase (PLGA micro-particles), containing a model antibacterial drug (vancomycin hydrochloride). In order to understand the key parameters ruling the performance of this delivery system, we developed a mathematical model able to discriminate the drug diffusion inside micro-particles and within the gel phase, eventually providing to predict the drug release kinetics. The model reliability was confirmed by fitting to experimental data, proposing as a powerful theoretical approach to design and optimize such in situ delivery systems.

Thermoreversible gelation and self-assembly behavior of dibenzylidene sorbitol in ternary solvent mixtures

The self-assembly behavior of 1,3:2,4-dibenzylidene-D-sorbitol (DBS) in ternary solvents has been systematically investigated for the use of kerosene gel in the aerospace propulsion. DBS forms a yield viscoelastic gels in a wide range of kerosene/hexanol/DMSO solvent concentrations despite the fact that DBS is incapable of gelling kerosene fuel. The gelation behavior of DBS in the solvent mixture is predicted using the Hansen solubility parameters. The polar parameter (δP) and hydrogen bonding (δH) parameter lie in the range of 1.96 ≤ δP ≤ 4.30 J0.5cm−1.5 and 3.40 ≤ δH ≤ 7.30 J0.5cm−1.5 respectively for the formation of gel in kerosene/hexanol/DMSO system. The phase transition temperature (Tf) of DBS gel is determined using temperature sweep measurement and predicted using modified Friedrich (MF) relation which is found be in close agreement with an average deviation of ± 10 °C. However, the deviation becomes larger when δP > 4.30 and δH > 7.30, in other words, with increase in the solvent polarity. As the solvent polarity or concentration of hexanol increases in the mixture, the gels exhibit a low Tf and $$ {G}_{max}^{\prime } $$ value because of the hindrance of self-assembling ability of DBS due to the intermolecular hydrogen bonding between DBS and solvents. The viscoelastic behavior of DBS gels is investigated using the oscillation sweep measurements and the storage modulus G′ is found to be higher than the loss modulus G″ for larger stress amplitude and frequency, indicating a solid-like nature of the gels. Furthermore, the microstructure analysis shows the presence of 3D nano-fibrillar morphology, which further depends on the solvent polarity. Microstructure changes from ‘rope-like’ fiber aggregate (Hex100; CH = 88 wt%) to a ‘web-like’ structures (Hex25; CH = 25 wt%), when the CH is decreased in the solvent mixture.

FORMULATION AND EVALUATION NASAL IN SITU GEL OF RIZATRIPTAN

Rizatraptan, a 5-HT antagonist is an anti migraine drug. Rizatriptan undergoes hepatic first pass metabolism, hence it shows poor bioavailability. In this study attempt has been done to improve bioavailability by formulating nasal in-situ gel. Formulation was developed to reduce the mucociliary clearance by using mucoadhesive polymer in gel, thereby increasing the contact of formulation with nasal mucosa and hence improving the absorption of drug. The in situ gel was formulated by using 2 factor (i.e.% of carbopol 934P and % of poloxamer 407) 3 level center composite design. All the formulated design point formulations exhibit thermo reversible gelation property. Gels were characterized by permeation studies, pH, % drug content, mucoadhesive force, gel strength, in vitro diffusion, ex vivo diffusion, stability study. Rheological study of gel formulation indicated that increase in polymer concentration increases the viscosity, gel strength was found in range of 110-130 sec., Spectral study revealed no interaction between drug and polymer. Various responses like T50%(Y1), T(80%Y2), ‘n’ of peppa’a equation(Y3), ‘k’ of first order and ‘n’ of higuchi (Y5) were analyzed to obtain optimized formulation. Optimized formulation(OF) followed first order drug diffusion and theoretically obtained drug release profile for 8 Hr. on the base of dose calculation Stability study indicates that there was no significant change in the Rizatriptan benzoate. Rizatriptan benzoate formulated as bioadhesive solution for nasal administration could have potential to avoid first pass effect than oral route, thus improve bio availability of drug and as a safe and sustained release nasal delivery system to control migraine

Drug-Loaded Biocompatible Nanocarriers Embedded in Poloxamer 407 Hydrogels as Therapeutic Formulations.

Hydrogels are three-dimensional networks of hydrophilic polymers able to absorb and retain a considerable amount of water or biological fluid while maintaining their structure. Among these, thermo-sensitive hydrogels, characterized by a temperature-dependent sol–gel transition, have been massively used as drug delivery systems for the controlled release of various bioactives. Poloxamer 407 (P407) is an ABA-type triblock copolymer with a center block of hydrophobic polypropylene oxide (PPO) between two hydrophilic polyethyleneoxide (PEO) lateral chains. Due to its unique thermo-reversible gelation properties, P407 has been widely investigated as a temperature-responsive material. The gelation phenomenon of P407 aqueous solutions is reversible and characterized by a sol–gel transition temperature. The nanoencapsulation of drugs within biocompatible delivery systems dispersed in P407 hydrogels is a strategy used to increase the local residence time of various bioactives at the injection site. In this mini-review, the state of the art of the most important mixed systems made up of colloidal carriers localized within a P407 hydrogel will be provided in order to illustrate the possibility of obtaining a controlled release of the entrapped drugs and an increase in their therapeutic efficacy as a function of the biomaterial used.

Dual delivery nanoscale device for miR-345 and gemcitabine co-delivery to treat pancreatic cancer

A polymeric dual delivery nanoscale device (DDND) was designed for combined delivery of microRNA (miR-345) and gemcitabine (GEM) to treat pancreatic cancer (PC). This temperature and pH-responsive pentablock copolymer system was able to restore miR-345, making xenograft tumors more susceptible to GEM, the standard therapy for PC. Restoration using DDND treatment results in sonic hedgehog signaling down regulation, which decreases desmoplasia, thereby resulting in improved GEM perfusion to the tumor and better therapeutic outcomes. The release of miR-345 and GEM could be tuned by using the DDND in the form of micelles or in the form of thermoreversible gels, based on polymer concentration. The DDNDs enabled miR-345 stability and sustained co-release of miR-345 and GEM, thereby facilitating dose-sparing use of GEM. Further, enhanced in vitro cellular uptake due to amphiphilic character, and endosomal escape because of the cationic end blocks led to efficient transfection with DDNDs. The combined DDND treatment enabled efficient reduction in cell viability of Capan-1 and CD18/HPAF cells in vitro compared with either GEM or miR-345 treatment alone. Mice carrying xenograft tumors treated with DDNDs carrying both miR-345 and GEM combination therapy displayed reduced tumor growth and less metastasis in distant organs compared to individual drug treatments. Immunohistochemical analysis of the xenograft tissues revealed significant down regulation of desmoplastic reaction, SHH, Gli-1, MUC4, and Ki67 compared to control groups.

Assessment of gelation behaviour of fenugreek gum and other galactomannans by dynamic viscoelasticity, fractal analysis and temperature cycle

Gelling properties of three galactomannan dispersions (fenugreek (FG), guar (GG) and locust bean gum (LBG)) were compared by strain and frequency sweep viscoelasticity, and temperature cycle at a constant strain and frequency in the concentration range 1 to 2 wt%. For FG and GG dispersions, tan δ remain <1 in the linear viscoelastic region during strain sweep analysis. FG and GG dispersions also showed a sol to gel transition at higher frequencies compared to LBG, indicating gelation by inter-polymer interactions and network formation. Conversely, strain and frequency sweep analysis of LBG dispersions revealed poor gelling ability. The fractal dimensions of the gels were 1.82, 2.38 for FG and 1.64, 2.10 for GG, using Shih (1990) and Wu-Morbidelli model (2001), respectively. According to the Shih model, FG and GG fell into the strong gel regime, but the Wu-Morbidelli model revealed that both dispersions were in the transition gel regime, more inclined towards weak gels, which is a more accurate description of the gels. FG and GG could form thermo-reversible gels, while for LBG, an improvement in gel strength was observed after the temperature cycle. The dynamic viscoelastic studies on FG dispersions support their use as food gelling agents.

Dual 0.02% chlorhexidine digluconate – 0.1% disodium EDTA loaded thermosensitive ocular gel for Acanthamoeba keratitis treatment

Poor bioavailability and low residence time limit the efficiency of conventional biguanide-based eye drops against Acanthamoeba keratitis. The aim of this work was to formulate an original anti-amoebic thermoreversible ocular gel combining biguanide and metalloproteases inhibitor - chelating agent. Chlorhexidine digluconate (CHX)-ethylenediaminetetraacetic acid disodium salt (Na2EDTA) were compounded in poloxamer 407 saline solution. 0.02% CHX - 0.1% Na2EDTA loaded thermosensitive ocular gel exhibited appropriate pH (5.73 ± 0.06), iso-osmolality (314 ± 5 mOsm/kg), viscosity (ranged between 15 and 25 mPa.s) and thermal gelation (26.5 °C and 33 °C) properties. Bioadhesion of gel was successfully tested onto isolated bovine eyes as well as the assessment of CHX penetration into the cornea. Intracorneal CHX concentration was found greater than trophozoite minimum amoebicidal concentration and minimal cysticidal concentration after 15-min and 2-h ocular exposure, respectively, while any CHX permeation through the cornea was detected (<51 ng/cm2/h). Improvement of CHX ocular bioavailability was attributed to probable solubilization of tear film lipid layer by poloxamer. In vitro efficiency of CHX-Na2EDTA ocular gel was confirmed from the drastic reduction of trophozoite and cyst survival (to 25% and 2%, respectively), confirming the potential of the multicomponent pharmaceutical material strategy for the treatment of Acanthamoeba keratitis.

Buccal epithelium Expanded and Encapsulated in Scaffold-Hybrid Approach to Urethral Stricture (BEES-HAUS) procedure: A novel cell therapy-based pilot study.

ObjectivesTo describe the feasibility of a novel cell‐based endoscopic technique using buccal epithelium, expanded and encapsulated in a thermoreversible gelation polymer scaffold for the treatment of urethral stricture.MethodsSix male patients with bulbar urethral stricture ranging from 2.0 to 3.5 cm in length were included in this pilot study. Autologous buccal epithelial cells from a small buccal mucosal biopsy were isolated, cultured and encapsulated in thermoreversible gelation polymer scaffold, and were implanted at the stricture site after a wide endoscopic urethrotomy.ResultsAll the patients voided well, with a mean peak flow rate of 24 mL/s. Urethroscopy carried out at 6 months showed healthy mucosa at the urethrotomy site. However, two of the six patients had recurrence at 18 and 24 months, respectively.ConclusionsThis endoscopic‐based Buccal epithelium Expanded and Encapsulated in Scaffold‐Hybrid Approach to Urethral Stricture (BEES‐HAUS) technique is a promising alternative for the open substitution buccal graft urethroplasty. It is possible to achieve the benefits of open substitution buccal urethroplasty with this endoscopic technique.