Usefulness of a murine model of hepatic cystic echinococcosis for preclinical drug trials: efficacy of albendazole vs albendazole nanocrystals.

Cystic echinococcosis is a zoonotic infection caused by the larval stage of Echinococcus granulosus sensu lato. The disease is characterized by the long-term growth of cysts, most commonly in the liver and lungs. Although an ideal model of cystic echinococcosis should induce the development of cysts in the liver and imitate the natural infection route, the murine model of intraperitoneal is still widely used in the field of experimental theraphy. The aim of the present work was to evaluate the usefulness of the murine model of hepatic CE for preclinical drug trials. The effectiveness of albendazole could also be assessed by measuring the diameter of the hepatic cyst. The albendazole significantly reduced the size of the cysts. The ultrastructural alterations of the germinal layer of hepatic cysts provoked by albendazole coincided with those observed in the intraperitoneal model. Similar results were obtained with both albendazole doses. Therefore, the efficacy of albendazole nanocrystals in the murine model of hepatic cystic echinococcosis was carried out at albendazole doses of 25 mg/kg. The abdominal ultrasound allows us to assess the response of cysts to drugs only in a qualitative manner. Although the size of cysts in the albendazole nanocrystal group was not significantly lower than that observed with albendazole, at the ultrastructural level, a greater extent of damage was observed. The murine model of hepatic cystic echinococcosis can be effectively used for assessing the effect of novel formulations or compounds. The main advantage of this model is that cysts are located in the orthotopic organ, which resembles the location most commonly found in human cases. In future studies, the usefulness of the model for pharmacokinetics studies in hepatic cysts will be evaluated.

Improved biodistribution and enhanced immune response of subunit vaccine using a nanostructure formed by self-assembly of ascorbyl palmitate.

New adjuvant strategies are needed to improve protein-based subunit vaccine immunogenicity. We examined the potential to use nanostructure of 6-O-ascorbyl palmitate to formulate ovalbumin (OVA) protein and an oligodeoxynucleotide (CpG-ODN) (OCC). In mice immunized with a single dose, OCC elicited an OVA-specific immune response superior to OVA/CpG-ODN solution (OC). Rheological studies demonstrated OCC's self-assembling viscoelastic properties. Biodistribution studies indicated that OCC prolonged OVA and CpG-ODN retention at injection site and lymph nodes, reducing systemic spread. Flow-cytometry assays demonstrated that OCC promoted OVA and CpG-ODN co-uptake by Ly6ChiCD11bhiCD11c+ monocytes. OCC and OC induced early IFN-γ in lymph nodes, but OCC led to higher concentration. Conversely, mice immunized with OC showed higher serum IFN-γ concentration compared to those immunized with OCC. In mice immunized with OCC, NK1.1+ cells were the IFN-γ major producers, and IFN-γ was essential for OVA-specific IgG2c switching. These findings illustrate how this nanostructure improves vaccine's response.

Design of a pilot plant-type pharmaceutical reactor to address the problem of interchangeability of generic semisolid formulations.

OBJECTIVE AND SIGNIFICANCE: This research aims to design and develop a pilot plant-type pharmaceutical reactor with a strong focus on its volumetric capacity and heat transfer capabilities. The primary goal is to replicate design and control strategies at the laboratory or pilot scale to analyze and produce generic semisolid formulations. METHODS: Computational fluid dynamics and heat transfer modeling, utilizing the finite volume method, were employed to determine the reactor's performance and particle trajectory during the mixing and stirring. This allowed for the establishment of optimal operational parameters and variables. Furthermore, prototypes were constructed at 1:2.5 and 1:15 scales to examine the reactor's morphology, ensure volumetric versatility, and conduct mixing, homogenization, and coloration tests using varying volumes. RESULTS AND CONCLUSIONS: The outcomes of this study yielded a versatile reactor suitable for processing pharmaceutical semisolids at both laboratory and pilot-scale volumes. Notably, the reactor demonstrated exceptional volumetric capacity within a single vessel while effectively facilitating heat transfer to its interior.

Naringin: Nanotechnological Strategies for Potential Pharmaceutical Applications.

Polyphenols comprise a number of natural substances, such as flavonoids, that show interesting biological effects. Among these substances is naringin, a naturally occurring flavanone glycoside found in citrus fruits and Chinese medicinal herbs. Several studies have shown that naringin has numerous biological properties, including cardioprotective, cholesterol-lowering, anti-Alzheimer's, nephroprotective, antiageing, antihyperglycemic, antiosteoporotic and gastroprotective, anti-inflammatory, antioxidant, antiapoptotic, anticancer and antiulcer effects. Despite its multiple benefits, the clinical application of naringin is severely restricted due to its susceptibility to oxidation, poor water solubility, and dissolution rate. In addition, naringin shows instability at acidic pH, is enzymatically metabolized by ß-glycosidase in the stomach and is degraded in the bloodstream when administered intravenously. These limitations, however, have been overcome thanks to the development of naringin nanoformulations. This review summarizes recent research carried out on strategies designed to improve naringin's bioactivity for potential therapeutic applications.

Design and production of 3D printed oral capsular devices for the modified release of urea in ruminants.

The use of 3D printing for the production of systems intended for oral delivery of diet supplements in the veterinary pharmacy constitutes an attractive technology that has remained unexplored. In this sense, this work studies the design and 3D printing of capsular devices that allow the modified release of urea, which is frequently used as a source of non-protein nitrogen in ruminants, but highly toxic if fast ingested. The devices were printed with combinations of polylactic acid (PLA, water-insoluble) and polyvinyl alcohol (PVA, water-soluble) in order to modulate the urea release through the different parts. The optimization of the designs as well as printing parameters such as extrusion temperature, printing speed, retraction distance and nozzle speed resulted critical to obtain successful capsular devices. In addition, the dissolution studies confirmed that the developed designs showed a controlled release of urea, especially the ones that presented internal partitions. Finally, Logistic and Weibull equations were the kinetic models that best fitted the experimental data corresponding to functions that describe S-shaped dissolution profiles. Overall, this work constitutes a proof of concept and provides the first steps in the development of 3D printed simple devices for the controlled release of supplements and drugs in veterinary pharmacy.

Nanocrystals as a master key to deliver hydrophobic drugs via multiple administration routes.

The poor aqueous solubility of many approved drugs and most new chemical entities poses a challenge to drug delivery scientists working in academic and industrial labs. Despite the high pharmacological activity these drugs may have, their limited water solubility leads to poor absorption and consequently to sub-therapeutic drug concentrations in target tissues. The formulation of drug nanocrystals (NCs) has emerged as one the most promising approaches for increasing the biopharmaceutical performance of hydrophobic drugs. Initially aimed at increasing the absorption of drugs administered orally, NCs have been increasingly utilised to allow drug delivery via multiple routes, namely, parenteral injections, transdermal, ocular, intranasal, and pulmonary. This review aims to describe the recent progress in the field and demonstrate how the NCs technology enabled the delivery of hydrophobic drugs through multiple administration routes.

Floating Ricobendazole Delivery Systems: A 3D Printing Method by Co-Extrusion of Sodium Alginate and Calcium Chloride.

At present, the use of benzimidazole drugs in veterinary medicine is strongly limited by both pharmacokinetics and formulative issues. In this research, the possibility of applying an innovative semi-solid extrusion 3D printing process in a co-axial configuration was speculated, with the aim of producing a new gastro-retentive dosage form loaded with ricobendazole. To obtain the drug delivery system (DDS), the ionotropic gelation of alginate in combination with a divalent cation during the extrusion was exploited. Two feeds were optimized in accordance with the printing requirements and the drug chemical properties: the crosslinking ink, i.e., a water ethanol mixture containing CaCl2 at two different ratios 0.05 M and 0.1 M, hydroxyethyl cellulose 2% w/v, Tween 85 0.1% v/v and Ricobendazole 5% w/v; and alginate ink, i.e., a sodium alginate solution at 6% w/v. The characterization of the dried DDS obtained from the extrusion of gels containing different amounts of calcium chloride showed a limited effect on the ink extrudability of the crosslinking agent, which on the contrary strongly influenced the final properties of the DDS, with a difference in the polymeric matrix toughness and resulting effects on floating time and drug release.

Synergistic Effect of Acetazolamide-(2-hydroxy)propyl ß-Cyclodextrin in Timolol Liposomes for Decreasing and Prolonging Intraocular Pressure Levels.

The purpose of this study was to design, for the first time, a co-loaded liposomal formulation (CLL) for treatment of glaucoma including timolol maleate (TM) in the lipid bilayer and acetazolamide (Acz)-(2-hydroxy)propyl ß-cyclodextrin (HPßCD) complexes (AczHP) solubilized in the aqueous core of liposomes. Formulations with TM (TM-L) and AczHP (AczHP-L), separately, were also prepared and characterized. A preliminary study comprising the Acz/HPßCD complexes and their interaction with cholesterol (a component of the lipid bilayer) was realized. Then, a screening study on formulation factors affecting the quality of the product was carried out following the design of the experiment methodology. In addition, in vitro release and permeation studies and in vivo lowering intraocular pressure (IOP) studies were performed. The results of the inclusion complexation behavior, characterization, and binding ability of Acz with HPßCD showed that HPßCD could enhance the water solubility of Acz despite the weak binding ability of the complex. Ch disturbed the stability and solubility parameters of Acz due to the fact of its competence by CD; thus, Chems (steroid derivative) was selected for further liposome formulation studies. The optimization of the lipid bilayer composition (DDAB, 0.0173 mmol and no double loading) and the extrusion as methods to reduce vesicle size were crucial for improving the physico-chemical properties and encapsulation efficiency of both drugs. In vitro release and permeation studies demonstrated that the CLL formulation showed improvement in in vitro drug release and permeation compared to the liposomal formulations with a single drug (TM-L and AczHP-L) and the standard solutions (TM-S and AczHP-S). CLL showed high efficacy in reducing and prolonging IOP, suggesting that the synergistic effect of TM and Acz on aqueous humor retention and the presence of this cyclodextrin and liposomes as permeation enhancers are responsible for the success of this strategy of co-loading for glaucoma therapy.

Biological drug therapy for ocular angiogenesis: Anti-VEGF agents and novel strategies based on nanotechnology.

Currently, biological drug therapy for ocular angiogenesis treatment is based on the administration of anti-VEGF agents via intravitreal route. The molecules approved with this purpose for ocular use include pegaptanib, ranibizumab, and aflibercept, whereas bevacizumab is commonly off-label used in the clinical practice. The schedule dosage involves repeated intravitreal injections of anti-VEGF agents to achieve and maintain effective concentrations in retina and choroids, which are administrated as solutions form. In this review article, we describe the features of different anti-VEGF agents, major challenges for their ocular delivery and the nanoparticles in development as delivery system of them. In this way, several polymeric and lipid nanoparticles are explored to load anti-VEGF agents with the aim of achieving sustained drug release and thus, minimize the number of intravitreal injections required. The main challenges were focused in the loading the molecules that maintain their bioactivity after their release from nanoparticulate system, followed the evaluation of them through studies of formulation stability, pharmacokinetic, and efficacy in in vitro and in vivo models. The analysis was based on the information published in peer-reviewed published papers relevant to anti-VEGF treatments and nanoparticles developed as ocular anti-VEGF delivery system.

Mucoadhesive and responsive nanogels as carriers for sustainable delivery of timolol for glaucoma therapy.

Topical administration to the eye for the treatment of glaucoma is a convenient route because it increases the patient comfort. Timolol can efficiently diminish the intraocular pressure (IOP) of the eye; however the topical application as a solution of timolol maleate (TM) has poor therapeutic index and presents severe side effects. The encapsulation of timolol in nanomaterials has appeared as a technology to increase its residence time in the eye thus achieving a sustained release and consequently diminishing the doses of this drug and their number. The preparation of nanogels (NGs) based on N-isopropylacrylamide (NIPA) and acrylic acid (AAc), easily synthesized by precipitation/dispersion free radical polymerization, is reported in this paper. Such NGs presented excellent dispersability in eye simulated fluid and ideal size for topical application. NGs can load efficiently timolol through ionic interaction, and the in vitro release showed that NGs deliver timolol in a sustained manner. In vivo sustained efficacy of the NGs-timolol nanoformulations was demonstrated in rabbit's glaucoma model, in which the IOP could be diminished and maintained constant for 48 h with only one application. Overall, the synthesized NGs in combination with timolol have potential as drug delivery system for glaucoma therapy.

Design of novel oral ricobendazole formulation applying melting solidification printing process (MESO-PP): An innovative solvent-free alternative method for 3D printing using a simplified concept and low temperature.

This paper describes a melting solidification printing process (MESO-PP) capable of obtaining printed oral solid dosage forms in a safe, versatile, and robust manner avoiding the use of solvents and high temperatures. MESO-PP and Gelucire® 50/13 (fatty polyethylene glycol esters) as ink can be used to obtain a floating sustained-release system with the aim of improving the dissolution and absorption of drugs, such as ricobendazole (RBZ), which have a low and erratic bioavailability. Gelucire 50/13 can be considered a good material to formulate inks using MESO-PP. As a model, the RBZ allowed us to assess that there were no changes in crystallinity and the API-ink interactions were ruled out using TGA, DSC, XRD and FT-IR assays. A batch of printlets, obtained using MESO-PP, fulfilled USP requirements regarding uniformity of mass (827 ± 9 mg) and drug content (211 ± 5 mg). Hardness and friability were 39.23 ± 9.65 N and 1.07 ± 0.5% respectively, just above the 1% USP tablet-friability limit. It was possible to obtain tablets of different sizes with high precision (r2 = 0.995). In vitro dissolution test showed that the printlet had a sustained-release of RBZ (only 7% after 15 min), that erosion was the predominant mechanism for drug release (n-value of Korsmeyer-Peppas equation = 0.991; r2 = 0.99) and that changes in the internal structures modify the release. Consequently, MESO-PP can be considered an excellent alternative to obtain solid pharmaceutical dosage forms with variable geometries for different pharmaceutical applications.

Ricobendazole nanocrystals obtained by media milling and spray drying: Pharmacokinetic comparison with the micronized form of the drug.

Helminthic infections are produced by different types of worms and affect millions of people worldwide. Benzimidazole compounds such as ricobendazole (RBZ) are widely used to treat helminthiasis. However, their low aqueous solubility leads to poor gastrointestinal dissolution, absorption and potential lack of efficacy. The formulation of nanocrystals (NCs) have become the strategy of preference for hydrophobic drugs. In this work, we prepared RBZ NCs (RBZ-NCs) by an optimized combination of bead milling and spray-drying. Following the physicochemical characterization, a comparative pharmacokinetic evaluation of RBZ-NCs was performed in dogs using as controls a micronized powdered form of RBZ (mRBZ) and a physical mixture of drug and stabilizer 1:1 (PM). The particle size of the redispersed RBZ-NCs was 181.30 ± 5.93 nm, whereas DSC, PXRD and FTIR analyses demonstrated that the active ingredient RBZ remained physicochemically unchanged after the manufacture process. RBZ-NCs exhibited improved in vitro biopharmaceutical behaviour when compared to mRBZ. Consequently, the pharmacokinetic trial demonstrated a significant increase in the drug oral absorption, with an AUC0-∞ 1.9-fold higher in comparison to that obtained in animals treated with mRBZ. This novel formulation holds substantial potential for the development of new/alternative treatments for helminth infections both in human and veterinary medicine.

Anti-echinococcal activity of menthol and a novel prodrug, menthol-pentanol, against Echinococcus multilocularis.

Alveolar echinococcosis is one of the most dangerous parasitic zoonoses. This disease, widely distributed in the northern hemisphere, is caused by the metacestode stage of the tapeworm Echinococcus multilocularis. All surgical and non-surgical patients should perform chemotherapy with benzimidazoles, mainly with albendazole. However, the efficacy of albendazole is variable due to its deficient pharmacokinetic properties. Therefore, the need to find new therapeutic alternatives for the treatment of alveolar echinococcosis is evident. Menthol is a natural compound of low toxicity, used in industries such as cosmetics and gastronomy and generally recognized as safe by the Food and Drug Administration. In addition, menthol has important pharmacological effects and is effective against a wide variety of organisms. The development of prodrugs allows improving the pharmacokinetic properties of the parental drug. To improve lipophilicity and therefore the bioavailability of menthol, a novel prodrug called menthol-pentanol was developed by masking the functional polar group of menthol by linking n-pentanol by a carbonate bond. The aim of the current work was to evaluate the in vitro and in vivo efficacy of menthol and menthol-pentanol against E. multilocularis. Menthol-pentanol had a greater protoscolicidal effect than menthol. In addition, the prodrug demonstrated a similar clinical efficacy to albendazole. The increase in lipophilicity of the prodrug with respect to menthol was reflected in an increase in its antiparasitic activity against E. multilocularis. Thus, menthol-pentanol appears as a promising candidate for further evaluation as a potential alternative for the treatment of alveolar echinococcosis.

Formulation and Evaluation of a Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), Nutraceutical Hydroalcoholic Suspension.

Ganoderma lucidum is a mushroom used in traditional Chinese medicine for its purported health benefits. Its complex chemical composition and potential synergies between bioactive compounds make it desirable to design a product that retains most of these compounds in a single formulation. In this article we evaluate a novel G. lucidum nutraceutical suspension (GNS) that reunites two fractions, an ethanolic extract and an aqueous extract, in a single oral liquid product. Back-to-back ethanolic and water extracts were mixed and the fraction that precipitates was recovered. The content of soluble solids, total triterpenoids, high molecular weight carbohydrates, and polyphenols was determined. A suspension was formulated by mixing the extracts and adding different concentrations of Carbomer® 940. The viscosity, physical stability, and particle size distribution were evaluated in all formulations. Almost 9% of the total extractives, consisting mostly of triterpenoids and phenolic compounds from the ethanolic extract, are insoluble in the hydroalcoholic mix and precipitate. This fraction can be suspended and kept stable with the aid of Carbomer® 940, a concentration between 0.5% and 1.0% showing adequate viscosity and particle size distribution. This preparation is an advantageous way of uniting the wide benefits of two G. lucidum extracts in a single oral liquid formulation.

Albendazole-lipid nanocapsules: Optimization, characterization and chemoprophylactic efficacy in mice infected with Echinococcus granulosus.

Cystic echinococcosis (CE), which is caused during the metacestode larval stage of Echinococcus granulosus, is a life-threatening disease and is very difficult to treat. At present, the FDA-approved antihelmintic drugs are mebendazole (MBZ), albendazole (ABZ) and its principal metabolite ABZ sulfoxide (ABZSO), but as these have a therapeutic efficacy over 50%, underlining the need for new drug delivery systems. The aim of this work was the optimization and characterization of previously developed ABZ lipid nanocapsules (ABZ-LNCs) and evaluate their efficacy in mice infected with E. granulosus. LNCs were prepared by the phase inversion technique and characterized in terms of size, surface charge, drug loading, and in vitro stability followed by an in vivo proof-of-concept using a murine model infected with E. granulosus. Stable particle dispersions with a narrow size distribution and high efficiency of encapsulation (≥90%) were obtained. ABZ-LNCs showed a greater chemoprophylactic efficacy than ABZ suspension administered by the oral route as 4 out of the 10 ABZ-LNCs treated mice did not develop any cysts, whereas the infection progressed in all mice from the ABZ suspension group. Regarding the ultrastructural studies of cysts, mice treated with ABZ-LNCs or ABZ suspension revealed changes in the germinal layer. However, the extent of the damage appeared to be greater after ABZ-LNC administration compared to the suspension treatment. These results suggest that ABZ-LNCs could be a promising novel candidate for ABZ delivery to treat CE.

Class-B CpG-ODN Formulated With a Nanostructure Induces Type I Interferons-Dependent and CD4+ T Cell-Independent CD8+ T-Cell Response Against Unconjugated Protein Antigen.

There is a need for new vaccine adjuvant strategies that offer both vigorous antibody and T-cell mediated protection to combat difficult intracellular pathogens and cancer. To this aim, we formulated class-B synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) with a nanostructure (Coa-ASC16 or coagel) formed by self-assembly of 6-0-ascorbyl palmitate ester. Our previous results demonstrated that mice immunized with ovalbumin (OVA) and CpG-ODN formulated with Coa-ASC16 (OVA/CpG-ODN/Coa-ASC16) elicited strong antibodies (IgG1 and IgG2a) and Th1/Th17 cellular responses without toxic systemic effects. These responses were superior to those induced by a solution of OVA with CpG-ODN or OVA/CpG-ODN formulated with aluminum salts. In this study, we investigated the capacity of this adjuvant strategy (CpG-ODN/Coa-ASC16) to elicit CD8+ T-cell response and some of the underlying cellular and molecular mechanisms involved in adaptive response. We also analyzed whether this adjuvant strategy allows a switch from an immunization scheme of three-doses to one of single-dose. Our results demonstrated that vaccination with OVA/CpG-ODN/Coa-ASC16 elicited an antigen-specific long-lasting humoral response and importantly-high quality CD8+ T-cell immunity with a single-dose immunization. Moreover, Coa-ASC16 promoted co-uptake of OVA and CpG-ODN by dendritic cells. The CD8+ T-cell response induced by OVA/CpG-ODN/Coa-ASC16 was dependent of type I interferons and independent of CD4+ T-cells, and showed polyfunctionality and efficiency against an intracellular pathogen. Furthermore, the cellular and humoral responses elicited by the nanostructured formulation were IL-6-independent. This system provides a simple and inexpensive adjuvant strategy with great potential for future rationally designed vaccines.

Albendazole nanocrystals in experimental alveolar echinococcosis: Enhanced chemoprophylactic and clinical efficacy in infected mice.

Human alveolar echinococcosis is caused by the fox tapeworm Echinococcus multilocularis and is usually fatal if left untreated. Medical treatment with albendazole (ABZ) remains an effective option. However, due to its low aqueous solubility, ABZ is poorly and erratically absorbed following oral administration resulting in low drug levels in plasma and liver distribution. Thus, there arises the need to find a simple, efficient and scalable method to produce new ABZ formulations with increased bioavailability. Bearing this in mind, ABZ nanocrystals (ABZ-NCs) appears to be a useful tool to achieve this goal. The aim of the current study was to investigate the chemoprophylactic and clinical efficacy of an ABZ-NC formulation on mice infected with E. multilocularis. In the chemoprophylactic efficacy study, mean weight of the cysts recovered from the ABZ-NC group was 50% lower than that recorded from untreated mice, whereas the treatment with ABZ suspension did not show preventive effect. The viability of protoscoleces isolated from ABZ-NC treated mice was significantly lower than control groups. In the clinical efficacy studies, both ABZ formulations resulted in a reduction in the mean weight of the cysts obtained from mice, however only the treatment with the nanosuspension revealed significant differences (P < 0.05) compared to the control groups. Treatment with ABZ-NCs reduced the weight of the cysts by 77% and the viability of their protoscoleces to 34%. All these results coincided with the tissue damage determined at the ultrastructural level. The enhanced chemoprophylactic and clinical efficacy of ABZ-NCs observed in this study could be attributed to an increase in the oral bioavailability of the drug. In a next step, we will characterize the cyst concentration profile after the administration of ABZ-NCs in mice infected with E. multilocularis.

Albendazole nanocrystals with improved pharmacokinetic performance in mice.

AIM: Albendazole (ABZ) is a broad-spectrum antiparasitic agent with poor aqueous solubility, which leads to poor/erratic bioavailability and therapeutic failures. Here, we aimed to produce a novel formulation of ABZ nanocrystals (ABZNC) and assess its pharmacokinetic performance in mice. Results/methodology: ABZNC were prepared by high-pressure homogenization and spray-drying processes. Redispersion capacity and solid yield were measured in order to obtain an optimized product. The final particle size was 415.69±7.40 nm and the solid yield was 72.32%. The pharmacokinetic parameters obtained in a mice model for ABZNC were enhanced (p < 0.05) with respect to the control formulation. CONCLUSION: ABZNC with improved pharmacokinetic behavior were produced by a simple, inexpensive and potentially scalable methodology.

Self-Assembling Elastin-Like Hydrogels for Timolol Delivery: Development of an Ophthalmic Formulation Against Glaucoma.

This work focuses on improving the effectiveness of current therapies against glaucoma by incorporating self-assembled polymers into the ophthalmic formulation. To that end, we first studied the influence of the dispersing medium on the mechanical performance of self-assembling elastin-like (EL) and silk-elastin-like (SEL) hydrogels by conducting rheological tests. These polymers were subsequently incorporated into the antiglaucoma formulation, which contains timolol maleate (TM) as active ingredient, and in vivo tests, namely adhesion tests and intraocular pressure measurements (IOP), were performed in New Zealand rabbits. An enhanced reduction in IOP due to the presence of the polymers was observed. Moreover, differences in the effectiveness between both EL- and SEL-hydrogels, which can be explained on the basis of the different rheological properties displayed by these two systems, were also encountered. The results point to the potential of this system as a basis for the development of an ophthalmic formulation against glaucoma.