Gel Dissolution Research Articles

Glutaraldehyde Cross-Linking of Salt-Induced Fibrinogen Hydrogels.

Covalent cross-linking is a common strategy to improve the mechanical properties of biological polymers. The most prominent field of application of such materials is in medicine, for example, in the form of bioprinting, drug delivery, and wound sealants. One biological polymer of particular interest is the blood clotting protein fibrinogen. In the natural process, fibrinogen polymerizes to fibrous hydrogel fibrin. Although the material shows great potential, its costs are very high due to the required enzyme thrombin. Recently, we introduced several approaches to trigger a thrombin-free fibrillogenesis of fibrinogen to a fibrin-like material. Inspired by the natural pathway of blood clotting in which covalent cross-linking stabilizes the clot, this "pseudofibrin" is now developed even further by covalently cross-linking the fibers. In particular, the effect of inexpensive glutaraldehyde on fiber morphology, rheological properties, and irreversible gel dissolution is investigated. Additionally, new insights into the reaction kinetics between fibrinogen and glutaraldehyde are gained. It could be shown that the fibrous structure of pseudofibrin can be retained during cross-linking and that glutaraldehyde significantly improves rheological properties of the hydrogels. Even more important, cross-linking with glutaraldehyde can prevent dissolution of the gels at elevated temperatures.

Effect of metakaolin on the chloride diffusion properties of alkali-activated slag in an acidic environment

Alkali-activated materials (AAMs) have good resistance to chemical corrosion compared to silicate cements, but the effect of the pH of chloride-containing solutions on the resistance of AAMs to chloride diffusion is not clear. In this paper, the resistance of alkali-activated slag (AAS) with different metakaolin replacement rate to chloride diffusion in HCl/NaCl solution was investigated in terms of mechanical properties, hydration product composition and pore structure. The experimental results show that acidic solutions lead to alkali leaching, and dissolution of gel and hydrotalcite. The capillary pores that appeared in the AAS after the replacement rate of 10% metakaolin resulted in a decrease in the average pore size of the AAS and low depth of chloride diffusion. 30% metakaolin replacement led to a decrease in the diffusion resistance. In HCl solution, the high [AlO4]5− retention corroded layer was observed in the AAS with 30% metakaolin replacement and this layer slowed down the migration rate of [Cl−]. This study shows the promising application of alkali-activated slag/metakaolin in complex chloride solution environments.

Bicarbonate-mediated dissolution of chitosan-based polyelectrolyte complex gels

Using chitosan/alginate polyelectrolyte complexes (PECs) as the primary model system, we demonstrate and systematically analyze mild and facile chitosan-based PEC gel dissolution in sodium bicarbonate (NaHCO3) solutions. The reversible conversion of chitosan amine groups to carbamate groups dissociates the ionic bonds between chitosan and its complexing polyanion while simultaneously solubilizing the dissociated chitosan, which causes the gels to dissolve. The PEC composition-dependent minimum NaHCO3 concentrations needed for this dissolution, for the materials examined herein, do not exceed a few hundred mM, and the dissolution rate increases with both the NaHCO3 concentration and the stoichiometric imbalance between the chitosan amine and alginate carboxylate groups within the PECs. The PEC dissolution rates also generally increase with the stirring speed but (depending on the PEC composition) can become insensitive to stirring when (1) the gels float and (2) at higher stirring speeds where transport of NaHCO3 to the PEC gel surface ceases to be a rate-determining step in the dissolution process. While the above effects are primarily demonstrated using chitosan/alginate PECs, extension of this NaHCO3-mediated dissolution approach to other chitosan-based PECs (i.e., those formed with synthetic polyanions) is also demonstrated. Collectively, these findings advance a non-destructive method of dissolving chitosan-based PEC gels (which could be advantageous for their compositional analysis or recycling) and provide guidelines for this method's application.

Influence of HIV-1 Genomic RNA on the Formation of Gag Biomolecular Condensates

Biomolecular condensates (BMCs) play an important role in the replication of a growing number of viruses, but many important mechanistic details remain to be elucidated. Previously, we demonstrated that the pan-retroviral nucleocapsid (NC) and HIV-1 pr55Gag (Gag) proteins phase separate into condensates, and that HIV-1 protease (PR)-mediated maturation of Gag and Gag-Pol precursor proteins yields self-assembling BMCs that have HIV-1 core architecture. Using biochemical and imaging techniques, we aimed to further characterize the phase separation of HIV-1 Gag by determining which of its intrinsically disordered regions (IDRs) influence the formation of BMCs, and how the HIV-1 viral genomic RNA (gRNA) could influence BMC abundance and size. We found that mutations in the Gag matrix (MA) domain or the NC zinc finger motifs altered condensate number and size in a salt-dependent manner. Gag BMCs were also bimodally influenced by the gRNA, with a condensate-promoting regime at lower protein concentrations and a gel dissolution at higher protein concentrations. Interestingly, incubation of Gag with CD4+ T cell nuclear lysates led to the formation of larger BMCs compared to much smaller ones observed in the presence of cytoplasmic lysates. These findings suggest that the composition and properties of Gag-containing BMCs may be altered by differential association of host factors in nuclear and cytosolic compartments during virus assembly. This study significantly advances our understanding of HIV-1 Gag BMC formation and provides a foundation for future therapeutic targeting of virion assembly.

Fabrication of pea protein gels with modulated rheological properties using high pressure processing

High pressure processing (HPP) as a non-thermal food preservation technology has recently received growing interest in protein processing. In the present study, the impact of high-pressure level, treatment time, protein concentration, and sample pH on the pea protein gel microstructure and strength were systematically investigated, as well as the protein conformation study, and the gel rheological and dissolution tests. A minimum of 10% and 15% (w/v) protein concentration was required for self-standing pea protein gel formation under 600 MPa and 300 MPa, respectively, at ambient temperature. The pH played an important role in affecting the gel microstructures and properties using HPP treatment. Particulate gels with compact structures and high mechanical strength up to 130 kPa were obtained at pH 5 mainly stabilized by hydrophobic interactions. Whereas fine-stranded gels mainly stabilized by hydrogen bonding with good elasticity and high water-holding capacity were formed at pH 7. The pH, HPP pressure level, and duration have been modulated to prepare a series of pea protein gels to mimic the texture of jelly, pudding, and tofu products. The tunable capacity using HPP makes pea protein a potential gelling ingredient in a wide range of food applications as a substitute for animal or soy protein. Furthermore, the gels treated with pH-shifting followed by HPP showed high freeze-thaw stability with a minimum syneresis level of 15% after two freeze-thaw cycles, demonstrating their potential to be used in frozen food products. Considering the advantages such as improved nutritional quality and extended shelf life compared to thermal technologies, HPP could be a promising non-thermal technique for the fabrication of pea protein gels with tunable rheological and mechanical properties to meet consumer needs for diversified texture and sensory quality.

Thermo-sensitive injectable hydrogel loading with elemene-loaded liposomes for enhanced anti-tumor effect.

Due to the heterogeneity and the complexity of the tumor microenvironment, combination therapy, especially the combination of chemotherapy and photothermal therapy (PTT), had received increasing attention. However, the co-delivery of small molecule drugs for chemotherapy and photothermal agents was a key issue. Herein, we prepared a novel thermo-sensitive hydrogel loading with elemene (ELE)-loaded and nano graphene oxide (NGO)-based liposomes for enhanced combined therapy. ELE was applied as the model drug for chemotherapy because it was a natural sesquiterpene drug with broad-spectrum and efficient antitumor activity. NGO was applied as drug carrier and photothermal agent simultaneously due to its two-dimensional structure and high photo-thermal conversion efficacy. NGO was further modified with glycyrrhetinic acid (GA) to improve its water dispersion, biocompatibility and tumor-targeting ability. ELE was loaded by GA-modified NGO (GA/NGO) to prepare the liposomes designated as ELE-GA/NGO-Lip, which was further mixed with chitosan (CS) solution and β-glycerin sodium phosphate (β-GP) solution to prepare the thermo-sensitive hydrogel designated as ELE-GA/NGO-Lip-gel. The obtained ELE-GA/NGO-Lip-gel had the gelling temperature of 37°C, temperature and pH-response gel dissolution and high photo-thermal conversion effect. More importantly, ELE-GA/NGO-Lip-gel upon 808nm laser irradiation had relative high anti-tumor efficiency against SMMC-7721 cells in vitro. This research might provide a potent platform for the application of thermos-sensitive injectable hydrogel in combined tumor therapy.

Impact of Poly (Vinyl Alcohol) on The Thermogelation Property and Drug Release Profile of Ophthalmic Formulations Based on Poloxamer 407

AbstractIn this study, we have designed and assessed a Ketorolac tromethamine (KT) based thermally responsive in situocular gelling system. These gelling systems consist of a thermally responsive in situ gelling polymer, poloxamer 407 (PM) and different molecular weight of poly (vinyl alcohol) (PVA) as release retardant. The formulations were analyzed for sol‐gel transition temperature, gelling aptitude, viscosity and rheological studies, gel morphology study, gel dissolution property and in vitro drug release study. FTIR spectral analysis was performed to explore any polymer‐polymer or drug‐polymer association. In comparison to commercially available drugs, the new formulations present a longer‐lasting drug release profile.

Gel transformation as a general strategy for fabrication of highly porous multiscale MOF architectures.

The structure and chemistry of metal-organic frameworks or MOFs dictate their properties and functionalities. However, their architecture and form are essential for facilitating the transport of molecules, the flow of electrons, the conduction of heat, the transmission of light, and the propagation of force, which are vital in many applications. This work explores the transformation of inorganic gels into MOFs as a general strategy to construct complex porous MOF architectures at nano, micro, and millimeter length scales. MOFs can be induced to form along three different pathways governed by gel dissolution, MOF nucleation, and crystallization kinetics. Slow gel dissolution, rapid nucleation, and moderate crystal growth result in a pseudomorphic transformation (pathway 1) that preserves the original network structure and pores, while a comparably faster crystallization displays significant localized structural changes but still preserves network interconnectivity (pathway 2). MOF exfoliates from the gel surface during rapid dissolution, thus inducing nucleation in the pore liquid leading to a dense assembly of percolated MOF particles (pathway 3). Thus, the prepared MOF 3D objects and architectures can be fabricated with superb mechanical strength (>98.7 MPa), excellent permeability (>3.4 × 10-10 m2), and large surface area (1100 m2 g-1) and mesopore volumes (1.1 cm3 g-1).

Mitochondria-targeting Type I AIE photosensitizer combined with H2S therapy: Uninterrupted hydroxyl radical generation for enhancing tumor therapy

Although Type I photosensitizers with aggregation-induced emission (AIE) characteristics have thrived as alternative tools for cancer photodynamic therapy (PDT) thanks to their efficient reactive oxygen species (ROS) generation and hypoxia resistance, accumulated reducing substances sinside the tumor and the short lifespan of ROS limit their therapeutic effects. How to continuously generate long-lasting ROS in tumors remains a thorny problem. Herein, we constructed an uninterrupted ROS generator by incorporating the H2S donor, (NH4)2S, and a Type I AIE photosensitizer, TDCAc, into an injectable agarose hydrogel, namely TSH. Mitochondria-targeting TDCAc exhibited excellent performance in multi-model Type I photodynamic/photothermal therapy under near-infrared laser irradiation. While (NH4)2S generates H2S gas in the acidic tumor microenvironment upon photothermal dissolution of TSH gel, which diffuses into cancer cells and effectively inhibits intracellular catalase activity. Thus, the intrinsic H2O2 consumption pathway is blocked to promote endogenous labile iron pool-mediated continuous hydroxyl radical (·OH) generation in tumors. In both in vitro and in vivo experiments, uninterrupted massive production of·OH in cancer cells after laser irradiation of TSH gels was demonstrated. Notably, H2S gas therapy is firstly combined with Type I AIE PDT, affording a novel synergistic strategy of continuous·OH generation for boosting tumor therapy.

Design and Optimization of In Situ Gelling Mucoadhesive Eye Drops Containing Dexamethasone.

Poor bioavailability of eye drops is a well-known issue, which can be improved by increasing the residence time on the eye surface and the penetration of the active pharmaceutical ingredient (API). This study aims to formulate in situ gelling mucoadhesive ophthalmic preparations. To increase the residence time, the formulations were based on a thermosensitive polymer (Poloxamer 407 (P407)) and were combined with two types of mucoadhesive polymers. Dexamethasone (DXM) was solubilized by complexation with cyclodextrins (CD). The effect of the composition on the gel structure, mucoadhesion, dissolution, and permeability was investigated with 33 full factorial design. These parameters of the gels were measured by rheological studies, tensile test, dialysis membrane diffusion, and in vitro permeability assay. The dissolution and permeability of the gels were also compared with DXM suspension and CD-DXM solution. The gelation is strongly determined by P407; however, the mucoadhesive polymers also influenced it. Mucoadhesion increased with the polymer concentration. The first phase of drug release was similar to that of the CD-DXM solution, then it became prolonged. The permeability of DXM was significantly improved. The factorial design helped to identify the most important factors, thereby facilitating the formulation of a suitable carrier for the CD-DXM complex.

A methacrylated hyaluronic acid network reinforced Pluronic F-127 gel for treatment of bacterial keratitis

In this study, we developed a novel in situ thermoresponsive gel by introducing crosslinked methacrylated hyaluronic acid (HA-MA) networks into Pluronic F-127 (PF-127) gel (HP gel) to achieve sustained levofloxacin (LFX) delivery in bacterial keratitis treatment. The interactions between PF-127 molecules and HA-MA networks were studied by scanning electron microscopy, rheology, dynamic light scattering, differential scanning calorimetry, and small angle x-ray scattering. The results showed that the HP gel exhibited a higher critical gelling temperature and lower viscosity than the PF-127 gel (P gel), and could form a uniform thin layer on the ocular surface. Moreover, the drug release profile and gel dissolution rate revealed that the HA-MA network could retard the diffusion and dissolution of drug molecules and prolong the drug release time, which corresponded to an enhanced antibacterial ability of the HP-LFX gel. Furthermore, the HP gel exhibited low cytotoxicity to human corneal epithelial cells. Finally, an in vivo pharmacodynamic study was conducted with rabbit keratitis models. An improved treatment efficacy was observed after application of the HP-LFX gels. This study highlights the potential of HP gels in ophthalmic drug delivery.

Influence of Minor Oil Components on Sunflower, Rice Bran, Candelilla, and Beeswax Oleogels

AbstractThe impact of the solvent composition on wax oleogels is addressed by (1) increasing polar components (PC) in sunflower and canola oil through thermal treatment and (2) removing minor components from untreated oils by column chromatography. Subsequently, oleogels are produced at 0.05 and 10 °C min−1 using 4% or 10% w/w of either sunflower, rice bran, candelilla, or beeswax. Oleogels firmness, break‐up behavior during amplitude sweeps, and gelation and dissolution are studied using penetration tests, rheology, and differential scanning calorimetry (DSC), respectively. Moreover, the crystal morphology of 4% w/w samples, gelled at 10 and 0.05 °C min−1, is studied using bright field microscopy. Distinct effects caused by the presence or absence of PCs on the characteristics mentioned above are observed, depending on the wax type. The formation of highly ordered wax crystal structures is favored in oils without PCs and low cooling rates. Data on gel formation and dissolution reveal a decrease in wax solubility in the absence of PCs. In contrast, the critical gelation concentration (CGC) decreases when PCs are present, independent of their concentration, indicating that PCs aid network formation. Moreover, the break‐up behavior during oscillatory stress is significantly different, leading to more network fragments and higher energy dissipation with increasing strain.Practical applications: It is found that the oil composition, in particular, the fatty acid composition of TAGs and dissolved minor polar oil components, profoundly affect wax oleogel properties. Although not all mechanisms leading to these changes can be unraveled within this study, a fundamental understanding of solvent composition's role on oleogel formation, dissolution, and network properties is vital in the light of product applications. Moreover, trustworthy and comparable oleogel research can only be achieved if the impact of solvent composition is considered in experiments. That way, the capability of oleogels for industrial applications might be maximized. For that, a detailed characterization of oil quality, particularly the fatty acid composition and presence of minor polar components, is required to conduct reliable scientific work in oleogel research.

Evaluation of hyaluronic acid gel dissolution with hyaluronidase in an in-vitro prostate cancer model

AimTo determine a dose response relationship of disintegration of a hyaluronic acid (HA) and hyaluronidase (HAS) used in prostate cancer radiotherapy. Materials and methodsFive in-vitro models are applicated with 3 ml (ml) HA. For dissolution varying doses of HAS were used: 6 ml, 3 ml, 1.5 ml, and 0 ml. One ml contains 150 International Units (IU). Each HAS was added with saline till the complementary amount of 6 ml. One phantom was solely implanted with a HA 3 ml acting as a control. Length, width and height were measured on different time points: 1st day 4 times, 2nd day 3 times, third day 2 times, and then once daily during one week, with a final measurement 2 weeks after implantation. The experiments were performed in duplicate to exclude variations and confirm the results. ResultsThe fastest dissolution was observed with the highest concentration of HAS, already observed at the first time point 2 h after implantation, with volume decrease of 50% on the second day, and less than 1 ml residue (33%) on day 4. The 2 other concentrations of HAS also showed a volume decrease, with less than 2 ml (66%) on day 4. All the applied quantities of HAS are observed with a residue of less than 1 ml after 7 days. After 14 days the control phantom and the saline filled one remains on steady state volume (3 ml). ConclusionsA dose response was observed by HAS injection: highest volumes of HAS dissolute most swiftly. Using a ratio of HA:HAS of 1:2 results in a decrease to half of initial volume within 24 h. This is of special interest when used in clinical practice following erroneous positioning, and dissolution is urgently needed.

Strength and durability properties of geopolymer paver blocks made with fly ash and brick kiln rice husk ash

In India the generation of agro waste rice husk ash is abundant. The utilization of rice husk ash in development of geopolymer binders can be suitable to alleviate the environmental problems associated with disposal of rice husk ash. Further, the utilization of rice husk ash generated from the stacks of brick kilns has not been addressed in past, particularly in development of geopolymer binders. This study proposes development of geopolymer paver (GEOPAV) blocks utilizing brick kiln rice husk ash (BKRHA). It presents fresh, mechanical and durability properties of GEOPAV blocks blended with fly ash, BKRHA, natural aggregates, NaOH and Na2SiO3 solution, and cured in both sundry and room temperature conditions. Microstructural analysis using scanning electron microscope (SEM) and X-ray diffraction (XRD) was adopted to study the influence of BKRHA on hardened properties of GEOPAV blocks. The results show that addition of BKRHA reduce the workability of GEOPAV mixes due to micro porous surface with honeycombed structure of BKRHA particles. The addition of BKRHA showed negligible improvement in compressive strength of GEOPAV blocks. However, the major advantage was observed with improved split tensile strength and flexural strength for GEOPAV blocks with BKRHA. Further, the durability properties in terms of resistance to acid and frost attack was significantly improved with the addition of BKRHA in GEOPAV blocks. Such improvements can be attributed to high amounts of amorphous silica in BKRHA which contribute towards dissolution and formation of polymeric gel, and thereby serve as a binder to enhance the geopolymer matrix making it dense. Finally, all the developed GEOPAV blocks satisfy the IS 15658–2021 specification requirements and perform much better when compared to commercially available paver blocks.

Development of Metronidazole-loaded In situ Thermosensitive Hydrogel for Periodontitis Treatment

Periodontal treatment focuses on the thorough removal of specific periodontal pathogens, mainly anaerobic Gram-negative bacteria, by mechanical scaling and root planning. In case the periodontal abscess is detected after treatment, a high dose of antimicrobial agents is commonly applied via oral administration. However, this approach increases the risk of antibiotic resistance and systemic side effects and decreases efficacy. To overcome the aforementioned issues, this study focused on the development of thermosensitive hydrogel to deliver the antibiotic drug metronidazole (MTZ) directly and locally to the oral infection site. The thermosensitive hydrogels were prepared by blending 28% w/v Pluronic F127 with various concentrations of methylcellulose (MC) and silk fibroin (SF). The gel properties, such as sol-gel transition time, viscosity, and gel strength, were investigated. The drug dissolution profiles, together with their theoretical models and gel dissolution characteristics, were also determined. All hydrogel formulations exhibited sol-gel transitions at 37°C within 1 min. An increase in MC content proportionally increased the viscosity but decreased the gel strength of the hydrogel. By contrast, the SF content did not significantly affect the viscosity but increased the gel strength of the hydrogel. The thermosensitive hydrogels also showed prolonged MTZ release characteristics for 10 days in phosphate-buffered saline (PBS) at pH 6.6, which followed the Higuchi diffusion model. Moreover, MTZ-thermosensitive hydrogel exhibited delayed dissolution in PBS at 37°C for more than 9 days. MTZ-thermosensitive hydrogels could be considered a prospective local oral drug delivery system to achieve efficient sustained release and improve the drug pharmacological properties in periodontitis treatment.

An Overview on Thermosensitive Oral Gel Based on Poloxamer 407.

In this review, we describe the application of thermosensitive hydrogels composed of poloxamer in medicine, especially for oral cavities. Thermosensitive hydrogels remain fluid at room temperature; at body temperature, they become more viscous gels. In this manner, the gelling system can remain localized for considerable durations and control and prolong drug release. The chemical structure of the poloxamer triblock copolymer leads to an amphiphilic aqueous solution and an active surface. Moreover, the poloxamer can gel by forming micelles in an aqueous solution, depending on its critical micelle concentration and critical micelle temperature. Owing to its controlled-release effect, a thermosensitive gel based on poloxamer 407 (P407) is used to deliver drugs with different characteristics. As demonstrated in studies on poloxamer formulations, an increase in gelling viscosity decreases the drug release rate and gel dissolution time to the extent that it prolongs the drug’s duration of action in disease treatment. This property is used for drug delivery and different therapeutic applications. Its unique route of administration, for many oral diseases, is advantageous over traditional routes of administration, such as direct application and systemic treatment. In conclusion, thermosensitive gels based on poloxamers are suitable and have great potential for oral disease treatment.

Monitoring the Degradation of Collagen Hydrogels by Collagenase Clostridium histolyticum.

Collagen-based hydrogels are investigated extensively in tissue engineering for their tunable physiochemical properties, biocompatibility and biodegradability. However, the effect of the integrity of the collagen triple helical structure on biodegradability is yet to be studied. In this study, we monitored the degradation of intact collagen (C-coll) and hydrolyzed collagen (D-coll) hydrogels in collagenase Clostridium histolyticum to understand their degradation process. Our results show that when peptides are present on the surface of the fibrils of D-coll hydrogels, cleavage of amide bonds occur at a much higher rate. The fibrillar structure of D-coll hydrogel results in a more pronounced breakdown of the gel network and dissolution of collagen peptides. The results from this work will improve the understanding of enzymatic degradation and the resulting bioabsorption of collagen materials used in drug delivery systems and scaffolds.

Temperature-sensitive gel-loaded composite nanomedicines for the treatment of cervical cancer by vaginal delivery.

In this study, toad venom (TV) and realgar were loaded into a poloxamer 188/407 (F127/F188)-based temperature-sensitive in situ gel (TISG) and encapsulated in solid lipid nanoparticles (TV-SLN) or ground nano-realgar (NR) to improve drug release and reduce local irritation after vaginal administration. The combination of TV-SLN and NR (TV-SLN/NR) greatly enhanced the inhibition of tumor cell proliferation and was most effective at a dose ratio of 2:3 (w/w). After TV-SLN/NR treatment, S and G0/G1 phase arrest were observed in HeLa and SKOV-3 cells and the inhibitory effects on proliferation were stronger than those in the conventional powder group. The gelation temperature of TV-SLN and NR-loaded TISG (TV-SLN/NR-TISG) using the selected formulation was 33±0.91°C. The cumulative release of the drug increased as the dissolution of gel progressed, showing a linear relationship (r>0.99). TV-SLN/NR-TISG enabled the sustained release of cargo by adhesion to the vaginal mucosa and showed excellent biocompatibility during continuous administration for 7days. We specifically demonstrated the effectiveness of the TISG for the vaginal delivery of TV-SLN and NR, supporting its important clinical implications for the treatment of cervical cancer.

Thermoresponsive sol-gel improves ocular bioavailability of Dipivefrin hydrochloride and potentially reduces the elevated intraocular pressure in vivo

The present study involves the development of Dipivefrin hydrochloride (DV) containing Poloxamers (P407 and P188)-Carbopol-934 (CP) based thermoresponsive-gels for the management of elevated intraocular pressure (IOP). Optimal formulation was evaluated for gelation temperature (Tgel), physicochemical and viscoelastic properties, in-vitro gel dissolution and drug release studies. The in-vivo safety, precorneal retention, ocular pharmacokinetics and efficacy in reducing IOP were also evaluated. Tgel of DV-containing thermoresponsive-gels were between 35.1 and 38.9 °C and it was Poloxamers and CP concentrations dependent. The optimal formulation (F8), composed of 20% P407, 5% P188 and 0.15% CP (w/v), had a Tgel of 35 °C. Its viscosity indicated good flow at room temperature and ability to convert to gel at ocular temperature and the rheology studies revealed favorable characteristics for its ocular use. In precorneal retention experiment, F8 indicated significantly higher area under concentrations curves as compared to DV-aqueous suspension (DV-AqS). In-vivo ocular pharmacokinetics indicated a significant improvement in ophthalmic bioavailability of epinephrine (active form of DV). F8 was non-irritant to the eyes and showed a successful, continuous and superior ability to reduce IOP compared to DV-AqS in rabbits. In conclusion, our developed system could be an appropriate substitute to the conventional DV eye preparations in the management of elevated IOP.

Rheo-dissolution: A new platform for the simultaneous measurement of rheology and drug release

There is great potential to improve drug delivery through the use of in-situ gelling delivery systems. Here we demonstrate a technique capable of measuring changes in rheology (gelation and/or dissolution) of in-situ gelling delivery systems on contact with physiological fluid, while simultaneously analysing drug release. An ocular in-situ gelling formulation (gellan and timolol maleate) and an in-situ gelling oral liquid (alginate and metronidazole) were used as exemplar formulations. The method allowed profiling of increasing gellan concentration resulting in a reduction of timolol maleate released into simulated lacrimal fluid. When alginate was used as an in-situ gelling oral formulation there was a rapid increase in Gʹ on contact with simulated gastric fluid. When this was changed to simulated intestinal fluid, drug release rate increased rapidly, coinciding with alginate gel dissolution. This work highlights the potential of this technology as a tool in development and optimisation of these increasingly popular delivery systems.