Design and Characterization of Ocular Inserts Loaded with Dexamethasone for the Treatment of Inflammatory Ophthalmic Disease.

The short precorneal residence time of ophthalmic drops is associated with their low absorption; therefore, the development of ocular inserts capable of prolonging and controlling the ophthalmic release of drugs is an interesting option in the design and development of these drugs. A surface response design was developed, specifically the Central Composite Design (CCD), to produce ophthalmic films loaded with Dexamethasone (DEX) by the solvent evaporation method having experimental levels of different concentrations of previously selected polymers (PVP K-30 and Eudragit RS100.). Once optimization of the formulation was obtained, the in vivo test was continued. The optimal formulation obtained a thickness of 0.265 ± 0.095 mm, pH of 7.11 ± 0.04, tensile strength of 15.50 ± 3.94 gF, humidity (%) of 22.54 ± 1.7, mucoadhesion strength of 16.89 ± 3.46 gF, chemical content (%) of 98.19 ± 1.124, release of (%) 13,510.71, and swelling of 0.0403 ± 0.023 g; furthermore, in the in vivo testing the number and residence time of PMN cells were lower compared to the Ophthalmic Drops. The present study confirms the potential use of polymeric systems using PVPK30 and ERS100 as a new strategy of controlled release of ophthalmic drugs by controlling and prolonging the release of DEX at the affected site by decreasing the systemic effects of the drug.

Synergistic Effect of Retinoic Acid and Lactoferrin in the Maintenance of Gut Homeostasis.

Lactoferrin (LF) is a glycoprotein that binds to iron ions (Fe2+) and other metallic ions, such as Mg2+, Zn2+, and Cu2+, and has antibacterial and immunomodulatory properties. The antibacterial properties of LF are due to its ability to sequester iron. The immunomodulatory capability of LF promotes homeostasis in the enteric environment, acting directly on the beneficial microbiota. LF can modulate antigen-presenting cell (APC) biology, including migration and cell activation. Nonetheless, some gut microbiota strains produce toxic metabolites, and APCs are responsible for initiating the process that inhibits the inflammatory response against them. Thus, eliminating harmful strains lowers the risk of inducing chronic inflammation, and consequently, metabolic disease, which can progress to type 2 diabetes mellitus (T2DM). LF and retinoic acid (RA) exhibit immunomodulatory properties such as decreasing cytokine production, thus modifying the inflammatory response. Their activities have been observed both in vitro and in vivo. The combined, simultaneous effect of these molecules has not been studied; however, the synergistic effect of LF and RA may be employed for enhancing the secretion of humoral factors, such as IgA. We speculate that the combination of LF and RA could be a potential prophylactic alternative for the treatment of metabolic dysregulations such as T2DM. The present review focuses on the importance of a healthy diet for a balanced gut and describes how probiotics and prebiotics with immunomodulatory activity as well as inductors of differentiation and cell proliferation could be acquired directly from the diet or indirectly through the oral administration of formulations aimed to maintain gut health or restore a eubiotic state in an intestinal environment that has been dysregulated by external factors such as stress and a high-fat diet.

Laponite Composites: In Situ Films Forming as a Possible Healing Agent.

A healing material must have desirable characteristics such as maintaining a physiological environment, protective barrier-forming abilities, exudate absorption, easy handling, and non-toxicity. Laponite is a synthetic clay with properties such as swelling, physical crosslinking, rheological stability, and drug entrapment, making it an interesting alternative for developing new dressings. This study evaluated its performance in lecithin/gelatin composites (LGL) as well as with the addition of maltodextrin/sodium ascorbate mixture (LGL MAS). These materials were applied as nanoparticles, dispersed, and prepared by using the gelatin desolvation method-eventually being turned into films via the solvent-casting method. Both types of composites were also studied as dispersions and films. Dynamic Light Scattering (DLS) and rheological techniques were used to characterize the dispersions, while the films' mechanical properties and drug release were determined. Laponite in an amount of 8.8 mg developed the optimal composites, reducing the particulate size and avoiding the agglomeration by its physical crosslinker and amphoteric properties. On the films, it enhanced the swelling and provided stability below 50 °C. Moreover, the study of drug release in maltodextrin and sodium ascorbate from LGL MAS was fitted to first-order and Korsmeyer-Peppas models, respectively. The aforementioned systems represent an interesting, innovative, and promising alternative in the field of healing materials.

Ceftriaxone-Loaded Polymeric Microneedles, Dressings, and Microfibers for Wound Treatment.

The objective of this study was to create polymeric dressings, microfibers, and microneedles (MN) loaded with ceftriaxone, using PMVA (Poly (Methyl vinyl ether-alt-maleic acid), Kollicoat® 100P, and Kollicoat® Protect as polymers to treat diabetic wounds and accelerate their recovery. These formulations were optimized through a series of experiments and were subsequently subjected to physicochemical tests. The results of the characterization of the dressings, microfibers, and microneedles (PMVA and 100P) were, respectively, a bioadhesion of 281.34, 720, 720, 2487, and 510.5 gf; a post-humectation bioadhesion of 186.34, 831.5, 2380, and 630.5 gf, tear strength of 2200, 1233, 1562, and 385 gf, erythema of 358, 8.4, 227, and 188; transepidermal water loss (TEWL) of 2.6, 4.7, 1.9, and 5.2 g/h·m2; hydration of 76.1, 89.9, 73.5, and 83.5%; pH of 4.85, 5.40, 5.85, and 4.85; and drug release (Peppas kinetics release) of n: 0.53, n: 0.62, n: 0.62, and n: 0.66). In vitro studies were performed on Franz-type diffusion cells and indicated flux of 57.1, 145.4, 718.7, and 2.7 µg/cm2; permeation coefficient (Kp) of 13.2, 19.56, 42, and 0.00015 cm2/h; and time lag (tL) of 6.29, 17.61, 27. 49, and 22.3 h, respectively, in wounded skin. There was no passage of ceftriaxone from dressings and microfibers to healthy skin, but that was not the case for PMVA/100P and Kollicoat® 100P microneedles, which exhibited flux of 194 and 0.4 µg/cm2, Kp of 11.3 and 0.00002 cm2/h, and tL of 5.2 and 9.7 h, respectively. The healing time of the formulations in vivo (tests carried out using diabetic Wistar rats) was under 14 days. In summary, polymeric dressings, microfibers, and microneedles loaded with ceftriaxone were developed. These formulations have the potential to address the challenges associated with chronic wounds, such as diabetic foot, improving the outcomes.

Chitosan Nanoparticles as Oral Drug Carriers.

The use of nanoparticles as drug delivery systems has increased in importance in the last decades. Despite the disadvantages of difficulty swallowing, gastric irritation, low solubility, and poor bioavailability, oral administration stands out as the most widely used route for therapeutic treatments, though it may not always be the most effective route. The effect of the first hepatic pass is one of the primary challenges that drugs must overcome to carry out their therapeutic effect. For these reasons, controlled-release systems based on nanoparticles synthesized from biodegradable natural polymers have been reported to be very efficient in enhancing oral delivery in multiple studies. Chitosan has been shown to have an extensive variability of properties and roles in the pharmaceutical and health fields; of its most important properties are the ability to encapsulate and transport drugs within the body and enhance the drug interaction with the target cells, which improves the efficacy of the encapsulated drugs. The physicochemical properties of chitosan give it the ability to form nanoparticles through multiple mechanisms, which will be addressed in this article. The present review article focuses on highlighting the applications of chitosan nanoparticles for oral drug delivery.

Development, Characterization, Optimization, and In Vivo Evaluation of Methacrylic Acid-Ethyl Acrylate Copolymer Nanoparticles Loaded with Glibenclamide in Diabetic Rats for Oral Administration.

The methacrylic acid-ethyl acrylate copolymer nanoparticles were prepared using the solvent displacement method. The independent variables were the drug/polymer ratio, surfactant concentration, Polioxyl 40 hydrogenated castor oil, the added water volume, time, and stirring speed, while size, PDI, zeta potential, and encapsulation efficiency were the response variables analyzed. A design of screening experiments was carried out to subsequently perform the optimization of the nanoparticle preparation process. The optimal formulation was characterized through the dependent variables size, PDI, zeta potential, encapsulation efficiency and drug release profiles. In vivo tests were performed in Wistar rats previously induced with diabetes by administration of streptozotocin. Once hyperglycemia was determined in rats, a suspension of nanoparticles loaded with glibenclamide was administered to them while the other group was administered with tablets of glibenclamide. The optimal nanoparticle formulation obtained a size of 18.98 +/- 9.14 nm with a PDI of 0.37085 +/- 0.014 and a zeta potential of -13.7125 +/- 1.82 mV; the encapsulation efficiency was of 44.5%. The in vivo model demonstrated a significant effect (p < 0.05) between the group administered with nanoparticles loaded with glibenclamide and the group administered with tablets compared to the group of untreated individuals.

Liberación de pravastatina sódica formulada en matrices poliméricas a base de Quitosan/Pluronic F ̶ 127 / Release of pravastine sodium formulated in polymer chitosan/pluronic f-127 matrices

Introducción: el desarrollo de medicamentos transdérmicos manifiesta gran interés en los últimos años debido a las ventajas que ofrece; sin embargo, muchos de los sistemas desarrollados utilizan componentes solubles lo cual podría llevar a una ineficacia terapéutica si la matriz polimérica del sistema se solubiliza muy rápido, por ello se ensayan polímeros insolubles que permitan modular la liberación de un ingrediente farmacéuticamente activo. Objetivo: evaluar la liberación de pravastatina sódica en matrices poliméricas insolubles de quitosan/PF-127 con el método de paleta sobre disco para obtener su perfil cinético de liberación, con la finalidad de proponerse como matrices viables para la elaboración de parches transdérmicos. Métodos: se realizaron estudios de contenido químico, diámetro y espesor de las películas, calorimetrías de barrido diferencial y estudios de liberación. La cuantificación del principio activo se realizó mediante espectrofotometría UV-Vis a 238 nm. Resultados: se obtuvieron parches transdérmicos con buena uniformidad de contenido, espesor, diámetro, con una buena estabilidad en base a los estudios de calorimetría. El uso de PF-127 incrementó o retardó la liberación de pravastatina de la matriz polimérica dependiendo de su concentración y al realizarse los perfiles cinéticos de liberación las formulaciones se ajustaron a una cinética de orden 0 que describe el comportamiento de algunos sistemas transdérmicos. Conclusiones: los resultados manifiestan la posibilidad de usar esta matriz polimérica insoluble de quitosana con PF-127 para modular la liberación de pravastatina sódica y de fármacos con estructura similar a la misma por vía transdérmica, lo que generará de esta manera nuevas alternativas a las formas farmacéuticas orales para el tratamiento de padecimientos y enfermedades(AU)

Introduction: the development of transdermal drugs has aroused great interest in recent years due to their advantages, however many of the drug delivery systems use soluble matrix components which could trigger therapeutic problems due to a rapid release of the active ingredient. Therefore, insoluble polymers are being tested that can modulate the release of a pharmaceutically active ingredient. Objective: to evaluate the release of pravastatin sodium in insoluble polymer chitosan/PF-127 matrices by VER to obtain kinetic profile of release in order to submit them as viable systems for the manufacture of transdermal patches. Methods: studies on the chemical content, diameter and thickness of films, differential scanning calorimetry and release studies were performed. The UV-Vis spectrophotometry at 238 nm allowed quantitating the active principle. Results: transdermal patches with adequate uniform drug content, suitable thickness and diameter with good stability, based on calorimetric studies, were obtained. The use of PF-127 increased or delayed the release of pravastatin sodium from the polymeric matrix depending on concentration. When performing the kinetic profiles of release, the formulations were regulated to zero kinetic that describes the behavior of some transdernal systems. Conclusions: the results demonstrated the possibility of using these insoluble polymer chitosan/PF-127 matrices to modulate the release of pravastin sodium and of other structurally similar drugs, thus creating new alternatives to existing pharmaceutical oral forms for treatment of diseases(AU)

Microagujas y Transcutol® como promotores de la penetración transdérmica de sibutramina formulada en parche transdérmico / Microneedles and Transcutol® as transdermal penetration enhancers of sibutramine formulated in a transdermal patch

Introducción: la principal barrera de permeación que tenemos es la piel. A pesar de ser una barrera casi impermeable para la mayoría de sustancias, se han buscado maneras para mejorar su permeabilidad utilizando nuevas tecnologías como es el uso de microagujas o promotores químicos como el Transcutol®. Objetivo: desarrollar y caracterizar un parche transdérmico a base de clorhidrato de sibutramina como fármaco modelo, usando Transcutol® y microagujas como agentes promotores de la penetración transdérmica. Métodos: se realizó la caracterización fisicoquímica de los parches mediante estudios de microscopia con luz polarizada, estudios de bioadhesión y resistencia a la ruptura. Los estudios de difusión se efectuaron en celdas de difusión verticales tipo Franz, utilizando piel abdominal humana como membrana entre ambos compartimentos. La cuantificación del principio activo se realizó mediante electroforesis capilar. Resultados: se obtuvieron parches bioadhesivos, con una adecuada estabilidad del activo en la matriz polimérica de quitosán al no precipitarse. El uso de Transcutol® y microagujas incrementó el paso de clorhidrato de sibutramina a través de piel humana con respecto al parche control. Se obtuvieron valores de flujo de 0,0649 mg.cm-2.h-1 y 0,0816 mg.cm-2.h-1 en el parche con agente promotor y microagujas de 1 y 2 mm respectivamente, en comparación con los valores de flujo de 0,0527 mg.cm-2.h-1 y 0,0554 mg.cm-2.h-1 para el parche sin agente promotor (control) utilizando microagujas de 1 y 2 mm respectivamente. Conclusiones: los resultados ponen de manifiesto la posibilidad de usar Transcutol® y microagujas para incrementar el paso de fármacos potentes y con estructura similar a la sibutramina por vía transdérmica, lo que genera de esta manera nuevas alternativas a las formas farmacéuticas orales para el tratamiento de padecimientos y enfermedades(AU)

Introduction: the main permeation barrier is the skin. Although it is almost an impermeable barrier to most substances, new ways have been examined to improve its permeability by using new technologies such as microneedles and chemical enhancers like Transcutol®. Objective: to develop and to characterize a transdermal patch containing sibutramine hydrochloride as model drug and using microneedles and Transcutol® as transdermal drug delivery enhancers. Methods: Physicochemical characterization of sibutramine hydrochloride patches using polarized light microscopy, bioadhesion, tensile strength studies. The diffusion studies were performed in Franz-type diffusion cells with human abdominal skin as a sort of membrane between both compartments. The active ingredient was quantified through capillary electrophoresis. Results: bioadhesive patches were obtained, with adequate stability of sibutramine hydrochloride in the polymer matrix of chitosan. The use of microneedles and Transcutol® increased sibutramine hydrochloride delivery through the human skin when compared with the control patch. The flow rates were 0.0649 mg.cm-2.h-1 and 0,0816 mg.cm-2.h-1 in the enhanced patch by using 1 and 2 mm microneedles respectively, in comparison with flow rates of 0,0527 mg.cm-2.h-1 and 0.0554 mg.cm-2.h-1 for the control patch having no enhancing agent with 1 and 2 mm microneedles respectively. Conclusions: the results show that it is possible to use Transcutol® and microneedles to increase the delivery of potent drugs having a structure similar to that of sibutramine through transdermal administration. All this generates new alternatives to oral pharmaceuticals in order to treat ailments and diseases(AU)

Preparation and characterization of triclosan nanoparticles intended to be used for the treatment of acne.

This work focuses on the preparation and characterization of nanoparticles containing triclosan. Additionally, in vitro percutaneous permeation of triclosan through pig ear skin was performed, and comparisons were made with two commercial formulations: An o/w emulsion and a solution, intended for the treatment of acne. The nanoparticle suspensions were prepared by the emulsification-diffusion by solvent displacement method, using Eudragit® E 100 as polymer. All batches showed a size smaller than 300 nm and a positive Zeta potential, high enough (20-40 mV) to ensure a good physical stability. Differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) studies suggested that triclosan was molecularly dispersed in the nanoparticle batches containing up to 31% of triclosan, with good encapsulation efficiency (95.9%). The results of the in vitro permeation studies showed the following order for the permeability coefficients: Solution>cream≈nanoparticles; while for the amount retained in the skin, the order was as follows: cream>nanoparticles≈solution. Nanoparticles, being free of surfactants or other potentially irritant agents, can be a good option for the delivery of triclosan to the skin, representing a good alternative for the treatment of acne.

In vivo skin permeation of sodium naproxen formulated in pluronic F-127 gels: effect of Azone and Transcutol.

The objective of this study was to determine the penetration of sodium naproxen, formulated in Pluronic F-127 (PF-127) gels containing Azone and Transcutol as penetration enhancers, through human skin in vivo. It was found that the combination of Azone and Transcutol in PF-127 gels enhanced sodium naproxen penetration, with enhancement ratios of up to two fold compared with the formulation containing only Transcutol. These results were confirmed by TEWL and ATR-FTIR spectroscopy, suggesting a synergic action for Azone and Transcutol. Because of the thermo-reversible behavior of Pluronic gels, the influence of the components added to the gel formulations on viscosity, as a function of temperature, was also studied.