RESUMO
Lidocaine is generally recognized and preferred for local anaesthesia, but in addition, studies have described additional benefits of lidocaine in cancer therapy, inflammation reduction, and wound healing. These properties contribute to its increasing importance in dermatological applications, and not only in pain relief but also in other potential therapeutic outcomes. Therefore, the purpose of our study was to enhance lidocaine delivery through the skin. A stable nanostructured lipid carrier (NLC), as a passive permeation enhancer, was developed using a 23 full factorial design. The nanosystems were characterized by crystallinity behaviour, particle size, zeta potential, encapsulation efficiency measurements, and one of them was selected for further investigation. Then, NLC gel was formulated for dermal application and compared to a traditional dermal ointment in terms of physicochemical (rheological behaviour) and biopharmaceutical (qualitative Franz diffusion and quantitative Raman investigations) properties. The study also examined the use of 3D printed solid microneedles as active permeation enhancers for these systems, offering a minimally invasive approach to enhance transdermal drug delivery. By actively facilitating drug permeation through the skin, microneedles can complement the passive transport achieved by NLCs, thereby providing an innovative and synergistic approach to improving lidocaine delivery.
Assuntos
Administração Cutânea , Anestésicos Locais , Lidocaína , Permeabilidade , Absorção Cutânea , Pele , Lidocaína/administração & dosagem , Lidocaína/farmacocinética , Lidocaína/química , Absorção Cutânea/efeitos dos fármacos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacocinética , Anestésicos Locais/química , Animais , Pele/metabolismo , Lipídeos/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/química , Nanoestruturas/administração & dosagem , Suínos , Agulhas , Tamanho da Partícula , GéisRESUMO
Cystinosis is a low-prevalence lysosomal storage disease. The pathomechanism involves abnormal functioning of the cystinosine lysosomal cystine transporter (CTNS), causing intraliposomal accumulation of the amino acid cysteine disulfide, which crystallizes and deposits in several parts of the body. The most common ophthalmic complication of cystinosis is the deposition of "gold dust" cystine crystals on the cornea, which already occurs in infancy and leads to severe photosensitivity and dry eyes as it gradually progresses with age. In the specific treatment of cystinosis, preparations containing cysteamine (CYA) are used. The availability of commercialized eyedrops for the targeted treatment is scarce, and only Cystadrops® are commercially available with strong limitations. Thus, magistral CYA-containing compounded eyedrops (CYA-CED) could have a key role in patient care; however, a rationally designed comprehensive study on the commercialized and magistral products is still missing. This work aims to build up a comprehensive study about commercialized and magistral CYA eye drops, involving pharmacokinetic and physicochemical characterization (applying mucoadhesivity, rheology test, investigation of drug release, and parallel artificial membrane permeability assays), as well as ex vivo tests, well supported by statistical analysis.
Assuntos
Cistinose , Humanos , Cistinose/metabolismo , Cisteamina/uso terapêutico , Cisteamina/metabolismo , Cistina/metabolismo , Soluções Oftálmicas/uso terapêutico , Córnea/metabolismoRESUMO
Nano-range bioactive colloidal carrier systems are envisaged to overcome the challenges associated with treatments of numerous diseases. Lipid nanoparticles (LNPs), one of the extensively investigated drug delivery systems, not only improve pharmacokinetic parameters, transportation, and chemical stability of encapsulated compounds but also provide efficient targeting and reduce the risk of toxicity. Over the last decades, nature-derived polyphenols, vitamins, antioxidants, dietary supplements, and herbs have received more attention due to their remarkable biological and pharmacological health and medical benefits. However, their poor aqueous solubility, compromised stability, insufficient absorption, and accelerated elimination impede research in the nutraceutical sector. Owing to the possibilities offered by various LNPs, their ability to accommodate both hydrophilic and hydrophobic molecules and the availability of various preparation methods suitable for sensitive molecules, loading natural fragile molecules into LNPs offers a promising solution. The primary objective of this work is to explore the synergy between nature and nanotechnology, encompassing a wide range of research aimed at encapsulating natural therapeutic molecules within LNPs.
Assuntos
Suplementos Nutricionais , Nanopartículas , Disponibilidade Biológica , Lipossomos , Sistemas de Liberação de Medicamentos , Nanopartículas/químicaRESUMO
Nepafenac is a highly effective NSAID used for treating postoperative ocular inflammation and pain after cataract surgery and its advantage over conventional topical NSAIDs has been proved many times. However, Nevanac® is a suspension eye drop, which clearly lacks patient compliance causing irritation, blurred vision, foreign body sensation along with problematic dosage due to its sticky, inhomogeneous consistence. In this study, nepafenac containing eye drops were prepared using hydroxypropyl-ß-cyclodextrin to ensure complete dissolution of nepafenac, sodium hyaluronate to provide mucoadhesion and adequate viscosity and a preservative-free officinal formula, Oculogutta Carbomerae containing carbomer (just like Nevanac®), therefore providing a similar base for the new formulations. According to an experimental design, 11 formulations were tested in vitro including two reference formulations by measuring their viscosity, mucoadhesion, drug release and corneal permeability. Finally, two formulations were found promising and investigated further on porcine eyes ex vivo and corneal distribution of nepafenac was determined by RAMAN mapping. The results showed that one formulation possessed better bioavailability ex vivo than Nevanac® 0.1 % suspension, while the other formulation containing only 60 % of the original dose were ex vivo equivalent with Nevanac® opening the way to nepafenac-containing eye drops with better patient compliance in the future.
Assuntos
Ciclodextrinas , Animais , Suínos , Soluções Oftálmicas , Anti-Inflamatórios não Esteroides , Fenilacetatos , Inflamação/tratamento farmacológicoRESUMO
The therapeutic application of nasal powders requires the development of novel mucoadhesive excipients. Thiolated polymers exhibit significant potential for this purpose based on their increased mucoadhesion attributable to the formation of disulfide bonds between the polymer and mucus surface. A chitosan-cysteine (chit-cyst) conjugate was synthesized using 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide in aqueous solution. The synthetic yield and synthesis conditions were optimized, and the efficiency of the reaction was evaluated. Rheological measurements revealed that the polymer derivative exhibited increased mucoadhesive properties in comparison to chitosan powder. To characterize the polymer, a novel purity investigation method was developed and verified to investigate the residual l-cysteine content. The results revealed that l-cysteine was not detectable in the resultant polymer matrix. Based on the cytotoxicity studies, chit-cyst was found to be safe for nasal application. Thereafter, nasal powder formulations were prepared using the polymer and the antiparkinsonian drug levodopa methyl ester hydrochloride by freeze-drying to investigate their nasal applicability. Based on the in vitro studies, these powders might be suitable for reducing the off periods of Parkinson's disease because of their expected higher in vivo mucoadhesion.
Assuntos
Quitosana , Cistos , Antiparkinsonianos , Cisteína/química , Dissulfetos/química , Excipientes/química , Humanos , Polímeros/química , Pós , Compostos de Sulfidrila/químicaRESUMO
The present study aimed at developing a potential in situ gellable dexamethasone (DXM) eye drop. Poly(aspartic acid) (PASP) derivatives were synthesized with dual functionality to improve the solubility of DXM, and to achieve in situ gelation. First, amine-modified ß-cyclodextrin (CD) was attached to polysuccinimide (PSI), second, thiol functionalities were added by the reaction of cysteamine and succinimide rings. Finally, the PSI derivatives were hydrolysed to the corresponding PASP derivatives to get water-soluble polymers. Phase-solubility studies confirmed the complexation ability of CD-containing PASP derivatives. In situ gelation and the effect of the CD immobilization on this behaviour were characterized by rheological measurements. The solubilizing effect of CD was confirmed by kinetic solubility measurements, whereas in vitro corneal permeability assay (corneal-PAMPA) measurements were performed to determine in vitro permeability and flux values. The effect of the PASP derivatives on permeation strongly depended on chemical composition and polymer concentration.
Assuntos
Ciclodextrinas , Dexametasona , Sistemas de Liberação de Medicamentos , Géis , Peptídeos , Polímeros/química , SolubilidadeRESUMO
BACKGROUND: Cystic fibrosis (CF) is a life-threatening multiorgan genetic disease, particularly affecting the lungs, where recurrent infections are the main cause of reduced life expectancy. In CF, mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein impair transepithelial electrolyte and water transport, resulting in airway dehydration, and a thickening of the mucus associated with abnormal viscoelastic properties. Our aim was to develop a rheological method to assess the effects of hypertonic saline (NaCl) and NaHCO3 on CF sputum viscoelasticity in vitro, and to identify the critical steps in sample preparation and in the rheological measurements. METHODS: Sputum samples were mixed with hypertonic salt solutions in vitro in a ratio of either 10:4 or 10:1. Distilled water was applied as a reference treatment. The rheological properties of sputum from CF patients, and the effects of these in vitro treatments, were studied with a rheometer at constant frequency and strain, followed by frequency sweep tests, where storage modulus (G'), loss modulus (Gâ³) and loss factor were determined. RESULTS: We identified three distinct categories of sputum: (i) highly elastic (G' > 100,000 Pa), (ii) elastic (100,000 Pa > G' > 1000 Pa), and (iii) viscoelastic (G' < 1000). At the higher additive ratio (10:4), all of the added solutions were found to significantly reduce the gel strength of the sputum, but the most pronounced changes were observed with NaHCO3 (p < 0.001). Samples with high elasticity exhibited the greatest changes while, for less elastic samples, a weakening of the gel structure was observed when they were treated with water or NaHCO3, but not with NaCl. For the viscoelastic samples, the additives did not cause significant changes in the parameters. When the lower additive ratio (10:1) was used, the mean values of the rheological parameters usually decreased, but the changes were not statistically significant. CONCLUSION: Based on the rheological properties of the initial sputum samples, we can predict with some confidence the treatment efficacy of each of the alternative additives. The marked differences between the three categories suggest that it is advisable to evaluate each sample individually using a rheological approach such as that described here.
Assuntos
Fibrose Cística/fisiopatologia , Solução Salina Hipertônica/farmacologia , Bicarbonato de Sódio/farmacologia , Escarro/fisiologia , Elasticidade , Feminino , Humanos , Técnicas In Vitro , Masculino , Reologia , Manejo de Espécimes , ViscosidadeRESUMO
The aim of this study was to investigate whether and how the biological media which are in contact with silicone oil play a role in the silicone emulsification process. Commercially available Oxane 1300 silicone oil and potential hydrophilic phases of the emulsions in the eye (porcine aqueous humor, porcine vitreous and balanced salt solution) were investigated separately and in a mixture or emulsions by means of surface tension, rheological, zeta potential measurements and microscopic investigation. The surface tension of biological media (vitreous and aqueous humor) was significantly lower than that of non-biological media, especially in the case of aqueous humor, which indicates a remarkable emulsification tendency with these phases. The biological media are able to form both oil-in-water and water-in-oil emulsions, which can be observed in the clinical practice as well. It was established that the vitreous has a more expressed emulsification ability compared with the aqueous humor because smaller and more stable droplets can form with silicon oil when the vitreous is still there. It can be concluded that the vitreous has a higher impact on emulsification than the aqueous medium, which can predict that the vitreous remaining after vitrectomy has a key role in emulsion formation in the eye with silicone oil endotamponade.
Assuntos
Humor Aquoso/química , Soluções Isotônicas/química , Óleos de Silicone/química , Corpo Vítreo/química , Animais , Emulsões , Reologia , Tensão Superficial , Suínos , Vitrectomia/métodosRESUMO
BACKGROUND: One of the most compelling medical challenges of this century is the treatment of cancer and among them, skin cancer is the most common type. Thus, current treatments need to be renewed continuously to handle this challenge. OBJECTIVE: This review presents considerations which can be employed during the development of nanosized formulations dedicated to the topical treatment of skin cancer. We aimed to collect and organize literature data on the treatment options for skin cancer in order to determine the required quality attributes of an effective dermal anticancer formulation. METHOD: With the consideration of the Quality by Design (QbD) approach related to the development of new pharmaceutical formulations, a cost-saving process ensuring a high-quality product taking into account patient expectations, industrial and regulatory aspects can be achieved. Furthermore, this concept is highly recommended by regulatory agencies. RESULTS: Our work discusses the current therapies, active agents, drug carrier systems, and evaluation methods in connection with the treatment of skin cancer and outlines Critical Quality Attributes which need to be considered during the development of a nanosized dermal anticancer formulation. CONCLUSION: The first part of this review summarizes the most important topical treatment therapies for skin cancer and highlights the future therapeutic perspectives, focusing on the benefits of nanotechnology and dermal administration. The second part outlines the critical points of nanosized dermal anticancer formulation development in the view of QbD approach. Our research emphasizes the application of QbD method for a rationalized and more effective anticancer formulation development process.
Assuntos
Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Neoplasias Cutâneas/tratamento farmacológico , Administração Cutânea , Animais , Antineoplásicos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Humanos , Nanopartículas/administração & dosagem , Nanopartículas/químicaRESUMO
BACKGROUND: Electrochemotherapy is a novel treatment for cutaneous and subcutaneous tumors utilizing the combination of electroporation and chemotherapeutic agents. Since tumors have an increasing incidence nowadays as a result of environmental and genetic factors, electrochemotherapy could be a promising treatment for cancer patients. OBJECTIVE: The aim of this article is to summarize the novel knowledge about the use of electroporation for antitumor treatments and to present a new application of electrochemotherapy with a well-known plant derived antitumor drug betulinic acid. For the review we have searched the databases of scientific and medical research to collect the available publications about the use of electrochemotherapy in the treatment of various types of cancer. METHOD: By the utilization of the available knowledge, we investigated the effect of electroporation on the penetration of a topically applied betulinic acid formulation into the skin by ex vivo Raman spectroscopy on hairless mouse skin. RESULTS: Raman measurements have demonstrated that the penetration depth of betulinic acid can be remarkably ameliorated by the use of electroporation, so this protocol can be a possibility for the treatment of deeper localized cancer nodules. Furthermore, it proved the influence of various treatment times, since they caused different spatial distributions of the drug in the skin. CONCLUSION: The review demonstrates that electrochemotherapy is a promising tool to treat different kinds of tumors with high efficiency and with only a few moderate adverse effects. Moreover, it presents a non-invasive method to enhance the penetration of antitumor agents, which can offer novel prospects for antitumor therapies.
Assuntos
Antineoplásicos/farmacologia , Eletroporação , Pomadas/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Triterpenos/farmacologia , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Humanos , Pomadas/química , Triterpenos Pentacíclicos , Neoplasias Cutâneas/patologia , Triterpenos/química , Ácido BetulínicoRESUMO
Thiolated polymers are a promising new group of excipients, but their stability against atmospheric oxidation has not been investigated in detail, and only a few efforts have been made to improve their stability. The oxidation of the thiol groups in solutions of thiolated polymers may result in a decrease of mucoadhesion and unpredictable in situ gelation. The aims of our work were to study the stability of aqueous solutions of thiolated polymers and the effects of stabilizing agents. We investigated thiolated poly(aspartic acid) polymers stabilized with dithiothreitol, glutathione or acetylcysteine. The effects of these antioxidants on the gel structure, mucoadhesion and drug release were determined by means of scanning electron microscopy, swelling, rheology, adhesion and drug release tests. It was concluded that the stability of polymer solutions containing antioxidants is sufficient for one day. Polymers stabilized with dithiotreitol demonstrated fast swelling and drug release, but weaker mucoadhesion as compared with the other samples. Polymers stabilized with glutathione displayed the weakest cohesive properties, resulting in fast and uncontrolled drug release and moderate mucoadhesion. Acetylcysteine-stabilized polymers exhibited an optimum cross-linked structure, with free thiol groups ensuring polymer-mucin interactions, resulting in the best mucoadhesive properties.
Assuntos
Antioxidantes/química , Olho , Peptídeos/química , Compostos de Sulfidrila/química , Administração Oftálmica , Microscopia Eletrônica de Varredura , Oxirredução , ReologiaRESUMO
Besides the opioids the standard management of the World Health Organization suggests NSAIDs (non-steroidal anti-inflammatory drugs) alone or in combination to enhance analgesia in malignant and non-malignant pain therapy. The applicability of NSAIDs in a nasal formulation is a new approach in pharmaceutical technology. In order to enhance the nasal absorption of meloxicam (MX) as an NSAID, its salt form, meloxicam potassium monohydrate (MXP), registered by Egis Plc., was investigated in comparison with MX. The physico-chemical properties of the drugs (structural analysis, solubility and dissolution rate) and the mucoadhesivity of nasal formulations were controlled. In vitro and in vivo studies were carried out to determine the nasal applicability of MXP as a drug candidate in pain therapy. It can be concluded that MX and MXP demonstrated the same equilibrium solubility at the pH5.60 of the nasal mucosa (0.017mg/ml); nonetheless, MXP indicated faster dissolution and a higher permeability through the synthetic membrane. The animal studies justified the short Tmax value (15min) and the high AUC of MXP, which is important in acute pain therapy. It can be assumed that the low mucoadhesivity of MXP spray did not increase the residence time in the nasal cavity, and the elimination from the nasal mucosa was therefore faster than in the case of MX. Further experiments are necessary to prove the therapeutic relevance of this MXP-containing innovative intranasal formulation.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Absorção Nasal/efeitos dos fármacos , Tiazinas/administração & dosagem , Tiazinas/química , Tiazóis/administração & dosagem , Tiazóis/química , Administração Intranasal , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Masculino , Meloxicam , Absorção Nasal/fisiologia , Ratos , Ratos Sprague-Dawley , Solubilidade/efeitos dos fármacos , Tiazinas/metabolismo , Tiazóis/metabolismoRESUMO
The aim of the present work was the optimization of the transdermal delivery of a lyotropic liquid crystal genistein-based formulation (LLC-GEN). LLC was chosen as medium in view of the poor solubility of GEN in water. Membrane diffusion and penetration studies were carried out with a Franz diffusion cell, through a synthetic membrane in vitro, a chick chorioallantoic membrane ex ovo, and ex vivo excised human epidermis. Thereafter, LLC-GEN was combined with electroporation (EP) to enhance the transdermal drug delivery. The synergistic effect of EP was verified by in vivo ATR-FTIR and ex vivo Raman spectroscopy on hairless mouse skin.
RESUMO
Hyaluronic acid (HA) and its derivatives play important roles in many fields of therapy, such as arthritis treatment, plastic surgery, dermatology, otology, ophthalmology, etc. With a view to increase the beneficial properties of HA in ocular drug delivery, many types of chemical structural modifications have been performed. In the course of our research work, we characterized nanosized cross-linked - (CLNaHA), linear sodium hyaluronate (NaHA) and zinc-hyaluronate (ZnHA), as potential ocular drug delivery systems. The aim was to determine the influence of the structure on biocompatibility, mucoadhesion and drug release. The structure was characterized by means of rheology. The cytotoxicity of the samples was determined on rabbit corneal epithelial cells (RCE) by the MTT test. Mucoadhesion measurements were made by a rheological method in vitro and by tensile tests in vitro and ex vivo. The release of sodium diclofenac, a frequently used non-steroidal anti-inflammatory drug with low bioavailability, from the gels was determined with a vertical Franz diffusion cell. The results demonstrated that all three derivatives have adequate mucoadhesive properties and their rapid drug release profiles are beneficial in ocular therapy. Thanks to these properties, the bioavailability of the ophthalmic preparations can be increased, especially with the application of CLNaHA.
Assuntos
Adesivos/química , Sistemas de Liberação de Medicamentos/métodos , Géis/química , Ácido Hialurônico/química , Nanopartículas/química , Compostos Organometálicos/química , Adesivos/efeitos adversos , Animais , Materiais Biocompatíveis/efeitos adversos , Materiais Biocompatíveis/química , Disponibilidade Biológica , Sobrevivência Celular/efeitos dos fármacos , Diclofenaco/química , Diclofenaco/farmacocinética , Sistemas de Liberação de Medicamentos/efeitos adversos , Liberação Controlada de Fármacos , Epitélio Corneano/efeitos dos fármacos , Géis/efeitos adversos , Ácido Hialurônico/efeitos adversos , Nanopartículas/efeitos adversos , Compostos Organometálicos/efeitos adversos , Coelhos , ReologiaRESUMO
Using the skin as absorption site presents unique advantages that have facilitated the progression of transdermal drug delivery in the past decades. Efforts in drug research have been devoted to find a quick and reproducible model for predicting the skin permeation of molecules. The Parallel Artificial Membrane Permeability Assay (PAMPA) has been extended for prediction of transdermal permeation by developing a model with completely artificial membrane, which can mimic the permeation through the stratum corneum. The present study aims to extend the Skin PAMPA method for testing transdermal and local therapeutic patches. The original method was modified and seven commercially available transdermal and local therapeutic patches with four different active pharmaceutical ingredients (nicotine, fentanyl, rivastigmine and ketoprofen) were studied. Data were compared to the declared delivery rates that are indicated by the manufacturers. Ex vivo permeation study was also performed in order to compare the permeated amount of the released drugs obtained by the two methods. The flux across the artificial membrane as well as the human skin (ex vivo) has been calculated and compared to the in vivo flux deduced from the labelled delivery rate and the active area of the patches. The results suggest that Skin PAMPA system can serve as a useful tool for evaluation and classification of the transdermal patches.
Assuntos
Fentanila/administração & dosagem , Cetoprofeno/administração & dosagem , Membranas Artificiais , Nicotina/administração & dosagem , Rivastigmina/administração & dosagem , Absorção Cutânea , Pele/metabolismo , Tecnologia Farmacêutica/instrumentação , Administração Cutânea , Química Farmacêutica , Fentanila/química , Fentanila/metabolismo , Humanos , Técnicas In Vitro , Cetoprofeno/química , Cetoprofeno/metabolismo , Cinética , Modelos Biológicos , Nicotina/química , Nicotina/metabolismo , Permeabilidade , Rivastigmina/química , Rivastigmina/metabolismo , Solubilidade , Tecnologia Farmacêutica/métodos , Adesivo TransdérmicoRESUMO
OBJECTIVES: Thermosensitive chitosan/glycerophosphate (C/GP) solutions exhibiting sol-gel transition around body temperature were prepared to develop a class of injectable hydrogel platforms for the imaging and loco-regional treatment of hepatocellular carcinoma (HCC). Indocyanine green (ICG) was loaded in the thermosensitive solutions in order to assess their potential for the detection of tumor nodules by fluorescence. METHODS: The gel formation of these formulations as well as their gelling time, injectability, compactness and resistance of gel structure, gelling temperature, storage conditions, biodegradability, and in vitro dye release behavior were investigated. Ex vivo studies were carried out for preliminary evaluation using an isolated bovine liver. RESULTS: Gel strengths and gelation rates increased with the cross-link density between C and GP. These behaviors are more evident for C/GP solutions, which displayed a gel-like precipitation at 4°C. Furthermore, formulations with the lowest cross-link density between C and GP exhibited the best injectability due to a lower resistance to flow. The loading of the dye did not influence the gelation rate. ICG was not released from the hydrogels because of a strong electrostatic interaction between C and ICG. Ex vivo preliminary studies revealed that these injectable formulations remain in correspondence of the injected site. CONCLUSIONS: The developed ICG-loaded hydrogels have the potential for intraoperative fluorescence imaging and local therapy of HCC as embolic agents. They form in situ compact gels and have a good potential for filling vessels and/or body cavities.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Quitosana/química , Corantes/administração & dosagem , Sistemas de Liberação de Medicamentos , Glicerofosfatos/química , Verde de Indocianina/administração & dosagem , Neoplasias Hepáticas/diagnóstico , Implantes Absorvíveis , Animais , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Bovinos , Química Farmacêutica , Diagnóstico por Imagem , Implantes de Medicamento , Géis , Injeções Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Soluções Farmacêuticas , Temperatura , ViscosidadeRESUMO
The ophthalmic formulations on the market suffer from poor bioavailability, and it would therefore be useful to design a new formulation which is able to prolong the residence time and reduce the administration frequency. Polymer matrices which exhibit strong mucoadhesion are promising platforms in ocular drug delivery from the aspect of improved bioavailability. In the present study, an in situ gelling, mucoadhesive drug delivery system was fabricated from thiolated poly(aspartic acid) (ThioPASP). The thiol groups of ThioPASP are able to form disulphide linkages with the mucin glycoproteins and prolong the residence time on the eye. The effects of the thiol groups on the structure, swelling behaviour and mucoadhesive character of the gel and on the drug release profile were determined. The gel structure was characterized by means of rheology. The ThioPASP gel was demonstrated by rheology, tensile test and 'wash away' measurements to display strong mucoadhesion. The drug release from the ThioPASP gel was studied on a vertical Franz diffusion cell: a burst release of sodium diclofenac occurred in the first hour, followed by sustained release of the encapsulated drug for up to 24h. The results proved the importance of the presence of the thiol groups and suggested that a ThioPASP formulation can be useful as an in situ gelling, ocular dosage form.