Release Of Pilocarpine Research Articles

Amination-mediated nano eye-drops with enhanced corneal permeability and effective burst release for acute glaucoma treatment

The development of topical formulations with advanced functions to overcome the poor and sluggish permeability/bioavailability of traditional eye drops into interior of the eye is significantly important for efficient management of acute intraocular diseases. For the first time, we herein exploit the amination level effects of chitosan coatings for facilitating a fast penetration of ceria nanocapsules (NCs) through the corneal barriers followed by triggering an effective burst release of pilocarpine in a controlled manner. Specifically, high amination level can help to improve the permeability of the ceria NCs through corneal cell layers by ∼ 43 folds while endowing the carriers with the most effective burst release performance. In an experimental rabbit model of acute glaucoma, a single dose topical instillation of pilocarpine-loaded chitosan-coated ceria NCs could effectively reduce the extremely high intraocular pressures to normal, prevent damage of endothelium (precluding ∼ 98.7 % cell death), open the angle closure, and inhibit retinal degeneration (impeding ∼ 98 % of retinal axon loss) at 4 h post-treatment. These findings show a great promise for the development of nano eye-drops for efficient management of acute glaucoma and other acute diseases that need prompt treatments.

Effects of shell thickness of hollow poly(lactic acid) nanoparticles on sustained drug delivery for pharmacological treatment of glaucoma

Structural designing of carriers with extended drug release profiles is critically important for achieving long-acting drug delivery systems toward efficient managements of chronic diseases. Here, we present a strategy to exploit the effects of the shell thickness of hollow poly(lactic acid) nanoparticles (HPLA NPs) in sustained glaucoma therapy. Formulations based on pilocarpine-loaded HPLA NPs with tailorable shell thickness ranging from 10 to 100 nm were shown to be highly compatible with human lens epithelial cells in vitro and with rabbit eyes in vivo. Specifically, shell thickness regulated the release of pilocarpine, with thick shells (~70 to 100 nm) providing sustained drug release performance but limited drug-loading efficiency, whereas ultrathin shells (~10 nm) induced the opposite effects. Remarkably, moderately thick shells (~40 nm) showed the most effective release profile of pilocarpine (above the therapeutic levels of ~10 µg/mL for over 56 days). In a rabbit model of glaucoma, single intracameral administration of an HPLA NP-based formulation with shell thickness of ~40 nm sustainably alleviated ocular hypertension for over 56 days, consequently protecting the structural integrity of the corneal endothelium, preserving the electrophysiological functions of the retina, and attenuating retinal and optic nerve degeneration in progressively glaucomatous eyes. The findings therefore implied a promising use of shell thickness effects in the development of long-acting drug delivery systems for pharmacological treatment of chronic ocular diseases. Statement of SignificanceOwing to their large surface areas and modifiable structures, nanoparticles have been considered as a promising platform for drug delivery; however, achieving drug nanocarrier systems with reduced burst release and sustained therapeutic efficacy remains challenges. This work presents the first report on rational design of hollow poly(lactic acid) nanocarriers for tailoring the structure-property-function relationships toward effective treatment of glaucoma. The shell thickness of the hollow nanocarriers is demonstrated to have influential impacts on pilocarpine encapsulation efficiency and release profile, indicating that the most sustained delivery performance (maintaining the release of pilocarpine above therapeutic level over 56 days) can be obtained for the polymeric nanoparticles with moderate shell thickness of ~40 nm.

Localized Delivery of Pilocarpine to Hypofunctional Salivary Glands through Electrospun Nanofiber Mats: An Ex Vivo and In Vivo Study.

Dry mouth or xerostomia is a frequent medical condition among the polymedicated elderly population. Systemic pilocarpine is included in the first line of pharmacological therapies for xerostomia. However, the efficacy of existing pilocarpine formulations is limited due to its adverse side effects and multiple daily dosages. To overcome these drawbacks, a localized formulation of pilocarpine targeting the salivary glands (SG) was developed in the current study. The proposed formulation consisted of pilocarpine-loaded Poly(lactic-co-glycolic acid) (PLGA)/poly(ethylene glycol) (PEG) nanofiber mats via an electrospinning technique. The nanofiber mats were fully characterized for their size, mesh porosity, drug encapsulation efficiency, and in vitro drug release. Mat biocompatibility and efficacy was evaluated in the SG organ ex vivo, and the expression of proliferation and pro-apoptotic markers at the cellular level was determined. In vivo short-term studies were performed to evaluate the saliva secretion after acute SG treatment with pilocarpine-loaded nanofiber mats, and after systemic pilocarpine for comparison purposes. The outcomes demonstrated that the pilocarpine-loaded mats were uniformly distributed (diameter: 384 ± 124 nm) in a highly porous mesh, and possessed a high encapsulation efficiency (~81%). Drug release studies showed an initial pilocarpine release of 26% (4.5 h), followed by a gradual increase (~46%) over 15 d. Pilocarpine-loaded nanofiber mats supported SG growth with negligible cytotoxicity and normal cellular proliferation and homeostasis. Salivary secretion was significantly increased 4.5 h after intradermal SG treatment with drug-loaded nanofibers in vivo. Overall, this study highlights the strengths of PLGA/PEG nanofiber mats for the localized daily delivery of pilocarpine and reveals its potential for future clinical translation in patients with xerostomia.

Effect of deacetylation degree on controlled pilocarpine release from injectable chitosan-g-poly(N-isopropylacrylamide) carriers

Development of biodegradable thermogels as intracameral injectable carriers for ocular delivery of antiglaucoma medications can provide a better treatment modality with low dosing frequency than eye drop formulations. For the first time, this study investigates the effect of deacetylation degree (DD) of the polysaccharide component in chitosan-g-poly(N-isopropylacrylamide) (CN) carriers on controlled release of pilocarpine in the management of glaucoma. Our results showed that increasing the chitosan DD from 60.7% to 98.5% leads to enhanced biodegradation resistance of carrier and prolonged release profile of the drug. Significant DNA damage and caspase-3 activation could be detected in lens epithelial cell cultures exposed to CN made from highly deacetylated polysaccharides, indicating apoptosis-related cytotoxicity due to relatively high positive charge density of the graft copolymers. Postoperative outcomes demonstrated that long-term therapeutic efficacy in glaucomatous rabbits is governed by intraocular pressure changes in response to intracamerally administered pilocarpine-loaded CN, strongly suggesting the usefulness of deacetylation in this injectable drug delivery carrier.

Validation of Smart Nanoparticles as Controlled Drug Delivery Systems: Loading and pH-Dependent Release of Pilocarpine.

Micelles are good devices for use as controlled drug delivery systems because they exhibit the ability to protect the encapsulated substance from the routes of degradation until they reach the site of action. The present work assesses loading kinetics of a hydrophobic drug, pilocarpine, in polymeric micellar nanoparticles (NPs) and its pH-dependent release in hydrophilic environments. The trigger pH stimulus, pH 5.5, was the value encountered in damaged tissues in solid tumors. The new nanoparticles were prepared from an amphiphilic block copolymer, [(HEMA19%-DMA31%)-(FMA5%-DEA45%)]. For the present research, three systems were validated, two of them with cross-linked cores and the other without chemical stabilization. A comparison of their loading kinetics and release profiles is discussed, with the support of additional data obtained by scanning electron microscopy and dynamic light scattering. The drug was loaded into the NPs within the first minutes; the load was dependent on the degree of cross-linking. All of the systems experienced a boost in drug release at acidic pH, ranging from 50 to 80% within the first 48 h. NPs with the highest degree (20%) of core cross-linking delivered the highest percentage of drug at fixed times. The studied systems exhibited fine-tuned sustained release features, which may provide a continuous delivery of the drug at specific acidic locations, thereby diminishing side effects and increasing therapeutic rates. Hence, the studied NPs proved to behave as smart controlled drug delivery systems capable of responding to changes in pH.

Salivary stimulation by prolonged release of pilocarpine in Sjögren’s syndrome.

Introduction : Prolonged drug delivery in the oral cavity offers many advantages, such as reducing adverse effects. Pilocarpine is an FDA-approved parasympathomimetic drug for the treatment of glandular hypofunction; however, its adverse effects limit its use. Objective: To evaluate the stimulation of salivary flow by the use of pilocarpine-releasing films, as well as their effects on the symptoms of xerostomia and adverse effects in patients with Sjogren's syndrome (SS). Materials and methods: Hy­droxypropylmethylcellulose (Methocel K4MCR) films were prepared in 1% acetic acid and pilocarpine was added under magnetic stirring. The pH and thickness, as well as diffusion uniformity and kinetics of drug release per cm 2 were evaluated by spectrophotometry. The films were tested sublingually in 40 patients with Sjogren's syndrome for a period of two weeks. Changes in their salivary flow were evaluated by analyzing samples of total saliva. Additionally, patients were screened for symptoms of xerostomia and adverse effects. Results: The films had a pH of 2.91±0.035, a thickness of 0.06866±0.00152 μm, and a diffusion uniformity of 91% per cm 2 . Use of the films resulted in an increase in salivary flow in both primary and secondary Sjogren's syndrome, but this increase was only significant in primary SS. Conclusion : Films showed optimal physicochemical properties for their administration, and proved effective in stimulating salivary flow without causing adverse effects during their administration.

Chitosan-g-poly(N-isopropylacrylamide) copolymers as delivery carriers for intracameral pilocarpine administration

This study reports, for the first time, the development of a chitosan-g-poly(N-isopropylacrylamide) (Chi-PN) biodegradable in situ gelling delivery system for ocular pilocarpine administration through intracameral injection. The number of thermo-responsive polymer segments grafted onto the chitosan via carbodiimide-mediated formation of amide linkages was greatly affected by varying the feeding amount of carboxyl-terminated poly(N-isopropylacrylamide) in the synthesis, thereby determining the phase transition temperature and enzymatic degradability of Chi-PN materials. The increase in grafting ratio facilitated temperature triggered gelation and drug encapsulation at physiological conditions. Additionally, the slow biodegradation process of delivery carriers was responsible for the delayed pilocarpine release, which allowed that the drug concentration could reach minimum therapeutic level for treating glaucoma during 42days of the study. All of the synthesized Chi-PN carriers demonstrated good ocular biocompatibility with lens epithelial cell cultures. In a rabbit model of experimental glaucoma, the intraocular pressure-lowering and miotic as well as corneal endothelial preservation responses to pilocarpine strongly depended on the drug release profiles. It is concluded that injectable biodegradable chitosan-based thermogels can be potentially utilized as intracameral biomaterials for extended release of antiglaucoma medications and improved performance of delivery carriers.

The role of alkyl chain length of monothiol-terminated alkyl carboxylic acid in the synthesis, characterization, and application of gelatin-g-poly(N-isopropylacrylamide) carriers for antiglaucoma drug delivery.

Considering that glaucoma is a chronic disease that requires long-term medical therapy to preserve vision in patients, it is highly desirable to augment pharmacological bioavailability and govern release profile by tuning the properties of drug delivery carriers. For the first time, the present study provide striking evidence that the alkyl chain length of monothiol-terminated alkyl carboxylic acid related to the synthesis of biodegradable in situ gelling copolymers plays a key role in molecular functionalization of intracameral delivery systems for ocular administration and controlled release of antiglaucoma medications. The therapeutic efficacies in treating glaucomatous damage are in response to in vivo pilocarpine release profiles modulated by the carbon number of thermo-responsive polymer segment-mediated carrier hydrophobicity and degradability.

Gallic acid grafting effect on delivery performance and antiglaucoma efficacy of antioxidant-functionalized intracameral pilocarpine carriers

Functionalization of therapeutic carrier biomaterials can potentially provide additional benefits in drug delivery for disease treatment. Given that this modification determines final therapeutic efficacy of drug carriers, here, we investigate systematically the role of grafting amount of antioxidant gallic acid (GA) onto GN in situ gelling copolymers made of biodegradable gelatin and thermo-responsive poly(N-isopropylacrylamide) for intracameral delivery of pilocarpine in antiglaucoma treatment. As expected, increasing redox reaction time increased total antioxidant activities and free radical scavenging abilities of synthesized carrier biomaterials. The hydrophilic nature of antioxidant molecules strongly affected physicochemical properties of carrier materials with varying GA grafting amounts, thereby dictating in vitro release behaviors and mechanisms of pilocarpine. In vitro oxidative stress challenges revealed that biocompatible carriers with high GA content alleviated lens epithelial cell damage and reduced reactive oxygen species. Intraocular pressure and pupil diameter in glaucomatous rabbits showed correlations with GA-mediated release of pilocarpine. Additionally, enhanced pharmacological treatment effects prevented corneal endothelial cell loss during disease progression. Increasing GA content increased total antioxidant level and decreased nitrite level in the aqueous humor, suggesting a much improved antioxidant status in glaucomatous eyes. This work significantly highlights the dependence of physicochemical properties, drug release behaviors, and bioactivities on intrinsic antioxidant capacities of therapeutic carrier biomaterials for glaucoma treatment. Statement of SignificanceDevelopment of injectable biodegradable polymer depots and functionalization of carrier biomaterials with antioxidant can potentially provide benefits such as improved bioavailability, controlled release pattern, and increased therapeutic effect in intracameral pilocarpine administration for glaucoma treatment. For the first time, this study demonstrated that the biodegradable in situ gelling copolymers can incorporate different levels of antioxidant gallic acid to tailor the structure-property-function relationship of the intracameral drug delivery system. The systematic evaluation fully verified the dependence of phase transition, degradation behavior, drug release mechanism, and antiglaucoma efficacy on intrinsic antioxidant capacities of carrier biomaterials. The report highlights the significant role of grafting amount of gallic acid in optimizing performance of antioxidant-functionalized polymer therapeutics as new drug delivery platforms in disease treatment.

Physicochemical and antimicrobial evaluation of chitosan and hydroxypropyl methylcellulose films for prolonged release of pilocarpine

Introduccion: El uso local de administracion prolongada de farmacos en la cavidad oral proporciona multiples ventajas, aumentando la accion farmacologica en el sitio local deseable, reduccion de la dosis usual y disminucion de los efectos adversos. La pilocarpina es una droga colinergica aprobada por la FDA para el tratamiento de la hipofuncion glandular, sin embargo la amplitud de sus efectos adversos limitan su uso.Objetivo: Con el objetivo de analizar las propiedades fisico-quimicas de las biopeliculas se evaluo el pH, grosor, solubilidad, uniformidad y la capacidad de liberar prolongadamente pilocarpina, asi como su actividad antimicrobiana ante los dos microorganismos patogenos oportunistas en la hiposialia (Streptococcus mutans y Candida albicans).Metodologia: Se elaboraron biopeliculas de Quitosan e Hidroxipropilmetilcelulosa (Methocel K4MCR) en acido acetico al 1%, adicionadas con pilocarpina bajo agitacion magnetica, evaluando el pH, grosor y el tiempo de solubilidad en saliva artificial, asi como la uniformidad de difusion y cinetica de liberacion de la droga por cm2 mediante espectrofotometria (OD=420nm). Mediante difusion en disco se evaluo la actividad antimicrobiana ante Streptococcus mutans ATCC 700610 y Candida albicans ATCC 90029 en concentraciones encontradas en hiposalivacion (1.44 x 106 UFC y 1.2 x 103 UFC respectivamente).Resultados: Todas las biopeliculas, a excepcion de la formulacion Hidroxipropilmetilcelulosa e Hidroxipropilmetilcelulosa / Pilocarpina resultaron tener las propiedades fisico-quimicas optimas de manipulacion, manteniendo una uniformidad de difusion de la droga en 76% por cm2 con liberacion prolongada por 4 horas, sin mostrar actividad antimicrobiana en concentraciones de hiposalivacion.

Developing the Potential Ophthalmic Applications of Pilocarpine Entrapped Into Polyvinylpyrrolidone–Poly(acrylic acid) Nanogel Dispersions Prepared By γ Radiation

The aim of this study was to improve the stability and bioavailability of pilocarpine in order to maintain an adequate concentration of the pilocarpine at the site of action for prolonged period of time. Thus, pH-sensitive polyvinylpyrrolidone-poly(acrylic acid) (PVP/PAAc) nanogels prepared by γ radiation-induced polymerization of acrylic acid (AAc) in an aqueous solution of polyvinylpyrrolidone (PVP) as a template polymer were used to encapsulate pilocarpine. Factors affecting size and encapsulation efficiency were optimized to obtain nanogel suitable for entrapping drug efficiently. The PVP/PAAc nanogel particles were characterized by dynamic light scattering (DLS), zeta potential, Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM), and their size can be controlled by the feed composition and concentration as well as the irradiation dose. Pilocarpine was loaded into the nanogel particles through electrostatic interactions where the AAc-rich nanogels exhibited the highest loading efficiency. The transmittance, mucoadhesion, and rheological characteristics of the nanogel particles were studied to evaluate their ocular applicability. The in vitro release study conducted in simulated tear fluid showed a relatively long sustained release of pilocarpine from the prepared PVP/PAAc nanogel particles if compared with pilocarpine in solution.

Pilocarpine‐loaded poly(DL‐lactic‐co‐glycolic acid) nanoparticles as potential candidates for controlled drug delivery with enhanced ocular pharmacological response

AbstractThe poor corneal residence time of pilocarpine, an alkaloid extracted from the leaves of the Jaborandi plant, limits its ocular application. The aim of this study was to develop, characterize, and evaluate the potential of pilocarpine entrapped by poly(DL‐lactic‐co‐glycolic acid) (PLGA) nanoparticle carriers for ocular drug delivery. Pilocarpine‐loaded nanoparticles were prepared with a double‐emulsion (water in oil in water) method and characterized with transmission electron microscopy and X‐ray diffraction analysis. The nanoparticles exhibited an average size of 82.7 nm with an encapsulation efficiency of 57%. Stability studies showed the absence of agglomeration and constancy in the amount of drug entrapped; this indicated the solidity of these particles for long‐term use. The in vitro release studies conducted in simulated tear fluid showed the sustained release of pilocarpine. In vivo evaluation of the nanoparticles was done in a rabbit model with a miosis assay and compared to an equal dose of commercially available eye drops of pilocarpine (Pilocar drops). The in vivo miosis studies showed that the duration of miotic response increased by 40% for the nanoparticles and produced an almost 68% increase in total miotic response when compared to the eye drops. In conclusion, this study clearly demonstrated the potential of pilocarpine‐loaded PLGA nanoparticles for multiplying the therapeutic effect of ophthalmic drug delivery with enhanced bioavailability and pharmacological response. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Crosslinked Networks Based on Polysaccharides and Collagen for Pilocarpine Sustained Release

The paper presents the experimental studies regarding synthesis and characterization of hydrogels based on gellan (Gel)/chitosan (CS) and collagen (Col), obtained by crosslinking with glutaraldehyde (GLA). The influence of the polysaccharide content and GLA ratio on the final composition and swelling characteristics was evaluated. Hydrogels swelling analysis, in distilled water and phosphate buffer (PBS, pH 7.2) has shown higher swelling degrees at increased concentration of polysaccharide into hydrogels. In vitro release of pilocarpine has demonstrated the possibility to use gellan-collagen and chitosan-collagen hydrogels as ophthalmic drug delivery matrix.

High pH Tolerance of a Chitosan–PAA Nanosuspension for Ophthalmic Delivery of Pilocarpine

In this paper, nanoparticles composed of chitosan (CS) and poly(acrylic acid) (PAA) were prepared by template polymerization for use as ophthalmic drug carrier. Before the polymerization, hydrogen peroxide was used to cut down the molecular weight of chitosan to improve its solubility and tolerance of pH values in the physiological condition. We found that, as the hydrogen peroxide concentration increased up to 2 M, the reaction temperature was kept at 60°C and depolymerization for 2 h, the molecular weight of chitosan was cut down to 4.1 × 104 and its pH tolerance was increased up to 7.1. The modified chitosan (MCS) is expected to tolerate in neutral condition without any precipitation. MCS–PAA nanoparticles for use as an ophthalmic drug carrier were successfully prepared using template polymerization of acrylic acid in the modified chitosan solution. The particle size of the nanoparticles was significantly affected by the pH value of the medium. Both in vitro and in vivo studies reveal that the prepared nanoparticles either modified or unmodified have the better ability in sustaining the release of pilocarpine than the simulated tear fluid and commercial eye drops.

Design and evaluation of novel fast forming pilocarpine-loaded ocular hydrogels for sustained pharmacological response

Fast forming hydrogels prepared by crosslinking a poly(ethylene glycol) (PEG)-based copolymer containing multiple thiol (SH) groups were evaluated for the controlled ocular delivery of pilocarpine and subsequent pupillary constriction. Physical properties of the hydrogels were characterized using UV–Vis spectrophotometry, transmission electron microscopy (TEM), rheometry, and swelling kinetics. Pilocarpine loading efficiency and release properties were measured in simulated tear fluid. The hydrogel formulations exhibited high drug loading efficiency (~ 74%). Pilocarpine release was found to be biphasic with release half times of ~ 2 and 94 h, respectively, and 85–100% of the drug was released over 8-days. Pilocarpine-loaded (2% w/v) hydrogels were evaluated in a rabbit model and compared to a similar dose of drug in aqueous solution. The hydrogels were retained in the eye for the entire period of the study with no observed irritation. Pilocarpine-loaded hydrogels sustained pupillary constriction for 24 h after administration as compared to 3 h for the solution, an 8-fold increase in the duration of action. A strong correlation between pilocarpine release and pupillary response was observed. In conclusion, the current studies demonstrate that in situ forming PEG hydrogels possess the viscoelastic, retention, and sustained delivery properties required for an efficient ocular drug delivery system.

Controlled release gelatin hydrogels and lyophilisates with potential application as ocular inserts

Hydrogels and lyophilisates were obtained by chemical crosslinking of gelatin using N-hydroxysuccinimide and N, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride. The systems were characterized with respect to the degree of crosslinking, morphology, water uptake, in vitro drug release and biocompatibility studies. Pilocarpine hydrochloride, a drug for the treatment of glaucoma, was loaded by soaking in an aqueous solution containing the drug. In vitro, the released drug percentage varied between 29.2% and 99.2% in 8 h of study. The release data were fitted to the Korsmeyer–Peppas equation to calculate the release exponent, which indicated anomalous transport for the release of pilocarpine. The corneal endothelial cell culture tests indicated that the prepared biomaterials are not cytotoxic.

Pilocarpine-loaded chitosan-PAA nanosuspension for ophthalmic delivery

Chitosan-poly(acrylic acid) (CS-PAA) nanoparticles, to be used as ophthalmic drug carrier, were successfully prepared using template polymerization of acrylic acid (AA) in a chitosan solution. When the polymerization was done at 70°C for 45 min with a CS/AA weight ratio of 1:1, the surface structure of the prepared nanoparticles was most stable with the smallest mean diameter (92.0±7.5 nm) and a stable zeta potential (25.5±2.6 mV) in a buffer solution (pH 4.5). The size of the nanoparticles dramatically increased with the pH value of the medium. Both in vitro and in vivo studies revealed that the prepared nanoparticle suspension was better at sustaining the release of pilocarpine than either simulated tear fluid or commercial eye drops.

Production of pilocarpine in callus of jaborandi (pilocarpus microphyllus stapf)

Summary Jaborandi (Pilocarpus microphyllus) is the only known source of pilocarpine, and although this alkaloid is the only natural compound used to treat glaucoma, very little is known about its metabolism. Calluses obtained from petioles of P. microphyllus leaves were partially immersed in MS (Murashige and Skoog) liquid medium containing different pH levels (4.8, 5.8, and 6.8), nutrient concentration (MS normal basal medium concentration, absence of N, P, and K and three times normal concentrations), histidine and threonine (0.05, 0.15, and 0.75mM), NaCl (25 and 75mM) and polyethylene glycol (5 and 15%). Exposure to methyljasmonic acid (MJ) vapor was also investigated. The calluses were subjected to these conditions for 4 and 8d under gentle agitation in the dark. Some calluses were also kept under continuous light. Pilocarpine was identified in the liquid medium by liquid chromatography‐mass spectrometry/mass spectrometry. The alkaloid quantifications in the media and cells were carried out by high performance liquid chromatography (HPLC). The calluses maintained in the dark released the greatest quantities of pilocarpine into the medium. Methyljasmonate inhibited the release of pilocarpine in the medium. High pH (6.8), absence and excess of N, excess of P, and 0.75mM of histidine and threonine induced the highest production of the alkaloid.

Reacetylated chitosan/cashew gum gel: Preliminary study for potential utilization as drug release matrix

AbstractThe aim of this work was to characterize and investigate the potential of chitosan/cashew gum (CH/CG) gel for the controlled release of pilocarpine hydrochloride. Gels were prepared by reacetylation of CH with acetic anhydride, characterized by infrared spectroscopy, thermal analysis, and X‐ray diffraction. Swellings in water and in phosphate buffers were also investigated. The release of pilocarpine for CH and CH/CG gels was shown to be similar in the first 100 min, where about 60% of the pilocarpine was released. After this time, addition of CG to the gels decreases pilocarpine release rate in the medium. CH gel release was found to be dependent on pH values, a non‐Fickian mechanism was observed for the release at pH 2 and 7.4, while at pH 9.8, a Fickian (diffusion) mechanism took place. On the other hand the release of pilocarpine in CH/CG matrix occurred by Fickian mechanism, independent of the pH value. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 326–334, 2006

In situ gelling xyloglucan formulations for sustained release ocular delivery of pilocarpine hydrochloride

Thermoreversible gels formed in situ by aqueous solutions of an enzyme-degraded xyloglucan polysaccharide were evaluated as sustained release vehicles for the ocular delivery of pilocarpine hydrochloride. In vitro release of pilocarpine from gels formed by warming xyloglucan sols (1.0, 1.5 and 2.0% w/w) to 34 °C followed root-time kinetics over a period of 6 h. The miotic responses in rabbit following administration of xyloglucan sols were compared with those from in situ gelling Pluronic F127 sols and from an aqueous buffer solution containing the same drug concentration. Sustained release of pilocarpine was observed with all gels, the duration of miotic response increasing with increase of xyloglucan concentration. The degree of enhancement of miotic response following sustained release of pilocarpine from the 1.5% w/w xyloglucan gel was similar to that from a 25% w/w Pluronic F127 gel.