Cellulose Acetate Phthalate-Based pH-Responsive Cyclosporine A-Loaded Contact Lens for the Treatment of Dry Eye.

Cyclosporine A (CsA) as an eye drop is an effective treatment for dry eye. However, it has potential side effects and a short ocular residence time. To overcome these obstacles, we developed a cellulose acetate phthalate-based pH-responsive contact lens (CL) loaded with CsA (CsA-CL). The CsA was continuously released from the CsA-CL at physiological conditions (37 °C, pH 7.4) without an initial burst. CsA was well-contained in the selected storage condition (4 °C, pH 5.4) for as long as 90 days. In safety assays, cytotoxicity, ocular irritation, visible light transmittance, and oxygen permeability were in a normal range. CsA concentrations in the conjunctiva, cornea, and lens increased over time until 12 h. When comparing the therapeutic efficacy between the normal control, experimental dry eye (EDE), and treatment groups (CsA eye drop, naïve CL, and CsA-CL groups), the tear volume, TBUT, corneal fluorescein staining at 7 and 14 days, conjunctival goblet cell density, and corneal apoptotic cell counts at 14 days improved in all treatment groups compared to EDE, with a significantly better result in the CsA-CL group compared with other groups (all p < 0.05). The CsA-CL could be an effective, stable, and safe option for inflammatory dry eye.

Triphenylphosphonium Modified Mesoporous Silica Nanoparticle for Enhanced Algicidal Efficacy of Cyclohexyl-(3,4-dichlorobenzyl) Amine.

Mesoporous silica nanoparticles (MSNPs) have been widely used for the delivery of different hydrophilic and hydrophobic drugs owing to their large surface area and ease of chemical alteration. On the other hand, triphenylphosphonium cation (TPP+) with high lipophilicity has a great mitochondrial homing property that stimulates the internalization of drugs into cells. Therefore, we designed a TPP-modified MSNP to enhance the algicidal activity of our new algicidal agent cyclohexyl-(3,4-dichlorobenzyl) amine (DP92). In this study, algicidal activity was evaluated by assessing the growth rate inhibition of two harmful algal blooms (HABs), Heterosigma akashiwo and Heterocapsa circularisquama, after treatment with DP92-loaded MSNP or TPP-MSNP and DP92 in DMSO (as control). For H. akashiwo, the IC50 values of TPP-MSNP and MSNP are 0.03 ± 0.01 and 0.16 ± 0.03 µM, respectively, whereas the value of the control is 0.27 ± 0.02 µM. For H. circularisquama, the IC50 values of TPP-MSNP and MSNP are 0.10 ± 0.02 and 0.29 ± 0.02 µM, respectively, whereas the value of the control is 1.90 ± 0.09 µM. Results have indicated that TPP-MSNP efficiently enhanced the algicidal activity of DP92, signifying the prospect of using DP92-loaded TPP-MSNP as an algicidal agent for the superior management of HABs.

Extracellular Vesicles: The Next Frontier in Regenerative Medicine and Drug Delivery.

Extracellular vesicles (EVs) are nanosized membrane particles secreted by cells to convey intercellular information. In recent years, EVs have enticed scientists owing to their prevalent distribution, enormous possibility as therapeutic aspirants, and probable roles as disease biomarkers. As natural transporters in the endogenous communication system, they play a role in protein, lipid, miRNA, mRNA, and DNA transport. In this chapter, we recapitulate the roles of EVs in the vast field of regenerative medicine. This summary mainly describes the potential roles of EVs in the regeneration of extensively studied organs or tissues, such as the heart, kidney, lung, liver, skin, and hair. Furthermore, EV can also transport drugs and corroborate their uptake by target cells through endocytosis; therefore, this chapter also highlights the use of EVs in the field of drug delivery.

Preparation and Characterization of Celecoxib Nanosuspension Using Bead Milling.

The aim of this study is to develop nanosuspension for improved dissolution of poorly water-soluble celecoxib. We first prepared coarse suspension of celecoxib with Tween 80 and hydroxypropyl methylcellulose as stabilizers, and then fabricated nanosuspension using the bead milling technique. Depending on milling time, the physical properties of nanosuspension were evaluated by photon correlation spectroscopy (e.g., particle size and distribution) and scanning electron microscopy (SEM) (e.g., morphology). As results, the mean size of crystalline celecoxib particles was highly reduced (368.1±14.5 nm) as milling process proceeded comparing to celecoxib powder (6.5±1.0 µm). Morphology of milled celecoxib particles has changed considerably from bar-shape or plate-shape to needle-shape due to a high energy caused by milling. In the dissolution test, the celecoxib nanosuspension showed an improved dissolution profile at pH 1.2 compared to celecoxib powder (less than 1%). In contrast, 53.4% of celecoxib in nanosuspension was dissolved up to 30 minutes, demonstrating improved dissolution of celecoxib. Taken together, bead-milled nanosuspension could be an effective strategy that can improve the dissolution and bioavailability.

Properties of Heparinoids Premixed with Tumor-Derived Extracellular Vesicles.

Tumor-derived exosomes are bound and internalized to organ-specific cells, affecting metastasis. Heparan sulfate proteoglycans mediate the interaction between cells and exosomes. Exosome transfer to the recipient cell can be competitively blocked by heparinoids, because heparin is structurally similar to heparan sulfate. It is hypothesized that there may be structural requirements of heparinoids to attenuate the cellular uptake and metastatic activity of tumor-derived exosomes. Here, we compared the properties of unfractionated heparin (UFH), glycol-split UFH, low-molecular-weight heparin (LMWH), glycol-split LMWH, and ultra-LMWH premixed with A549-derived exosomes. Uptake of A549-derived exosomes (0.1 mg/mL) into BEAS-2B cells was significantly blocked by 0.4 mg/mL of heparinoids. Heparinoids attenuated migration of BEAS-2B cells stimulated by A549-derived exosomes. Glycol-split LMWH with no antifactor Xa activity exhibited the strongest antimigratory effects than other heparinoids. Thus, heparinoids with proper molecular weight and structure can inhibit tumor-derived exosomes, not proportionally to the anticoagulant activity.

Removing Control of Cyclodextrin-Drug Complexes Using High Affinity Molecule.

Nanostructured supramolecular assemblies with hydrophobic cavities are used for improving the solubility, bioavailability, and stability of poorly water soluble drugs. In particular, host-guest inclusion using 2-hydroxypropyl-beta-cyclodextrin (HP-ß-CD) is a typical approach in the pharmaceutical field. In this study, celecoxib (CXB), a cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug (NSAID), was used as the model drug (guest material) and effectively incorporated into HP-ß-CD (host material). After forming a complete complex of HP-ß-CD and CXB, 1-adamantylamine (ADA) was used to allow CXB to be released from the HP-ß-CD in a concentration-dependent manner. This was revealed from Fourier-transform infrared spectroscopy and drug dissolution studies. Notably, the use of ADA, which is a high-affinity guest molecule, with cyclodextrin accelerated the removal of CXB from the host material through the exchange of guest molecules. Taken together, the host-guest based approach using a second guest molecule is useful for regulating on-demand drug release and could therefore be a potential tool for biomedical applications.

Improved Dissolution and Oral Bioavailability of Celecoxib by a Dry Elixir System.

The purpose of this study was to develop and evaluate a dry elixir (DE) system for enhancing the dissolution rate and oral bioavailability of celecoxib. DE system has been used for improving solubility, oral bioavailability of poorly water-soluble drugs. The encapsulated drugs or solubilized drugs in the matrix are rapidly dissolved due to the co-solvent effect, resting in both an enhanced dissolution and bioavailability. DEs containing celecoxib were prepared by spray-drying method and characterized by morphology, drug/ethanol content, drug crystallinity, dissolution rate and oral bioavailability. The ethanol content and drug content in DE system could be easily altered by controlling the spraydrying conditions. The dissolution profile of celecoxib from DE proved to be much higher than that of celecoxib powder due to the nano-structured matrix, amorphous state and encapsulated ethanol. The bioavailability of celecoxib from DEs was compared with celecoxib powder alone and commercial product (Celebrex®) in rats. In particular, blood concentrations of celecoxib form DE formulation were much greater than those of native celecoxib and market product. The data demonstrate that the DE system could provide an useful solid dosage form to enhance the solubility, dissolution rate and oral bioavailability of celecoxib.

Intravenous Delivery of Xenon Incorporated in Thermosensitive Nano-Emulsions for Anesthesia.

Xenon anesthesia has several advantages over conventional anesthetics, however, it has not been widely used in clinical sites, since the cost and minimum alveolar concentration were higher than conventional inhalational anesthetics. The purpose of this study was to develop an optimum vehicle for stable intravenous delivery of xenon with sufficient concentration. Thermosensitive lipid based nano-emulsions (TS-LE) were prepared by blending medium chain triglyceride, polyethylene glycol-15-hydroxystearate, D-α tocopherol polyethylene glycol succinate and Poloxamer 188. Three folds higher xenon was loaded in TS-LE when it was prepared under 5.5 atm of xenon pressure compared to that under 1 atm of xenon pressure at 22 °C (11.4±0.7 vs. 3.82±0.34 mg/ml). Poloxamer 188 conferred thermosensitive viscosity and outer rigid structure on TS-LE, and the properties led to the enhanced stability of xenon compared to usual lipid emulsion. Induction of anesthesia was investigated by monitoring loss of forepaw righting reflex (LORR) in rats. The ED50 for LORR was 131.9 mg/kg and the anesthesia was maintained for 65.3±7.1 sec at a dose of 179 mg/kg in rats. When it is considered that TS-LE stably loads enough concentration of xenon for the induction of therapeutically sufficient anesthesia, TS-LE may be regarded as a promising candidate for intravenous xenon delivery.

Cefdinir Solid Dispersion Composed of Hydrophilic Polymers with Enhanced Solubility, Dissolution, and Bioavailability in Rats.

The aim of this work was to develop cefdinir solid dispersions (CSDs) prepared using hydrophilic polymers with enhanced dissolution/solubility and in vivo oral bioavailability. CSDs were prepared with hydrophilic polymers such as hydroxypropyl-methylcellulose (HPMC; CSD1), carboxymethylcellulose-Na (CMC-Na; CSD2), polyvinyl pyrrolidone K30 (PVP K30; CSD3) at the weight ratio of 1:1 (drug:polymer) using a spray-drying method. The prepared CSDs were characterized by aqueous solubility, differential scanning calorimetry (DSC), powder X-ray diffraction (p-XRD), scanning electron microscopy (SEM), aqueous viscosity, and dissolution test in various media. The oral bioavailability of CSDs was also evaluated in rats and compared with cefdinir powder suspension. The cefdinir in CSDs was amorphous form, as confirmed in the DSC and p-XRD measurements. The developed CSDs commonly resulted in about 9.0-fold higher solubility of cefdinir and a significantly improved dissolution profile in water and at pH 1.2, compared with cefdinir crystalline powder. Importantly, the in vivo oral absorption (represented as AUCinf) was markedly increased by 4.30-, 6.77- and 3.01-fold for CSD1, CSD2, and CSD3, respectively, compared with cefdinir suspension in rats. The CSD2 prepared with CMC-Na would provide a promising vehicle to enhance dissolution and bioavailability of cefdinir in vivo.

An extremely alkaline mannanase from Streptomyces sp. CS428 hydrolyzes galactomannan producing series of mannooligosaccharides.

An alkaline-thermostable mannanase from Streptomyces sp. CS428 was produced, purified, and biochemically characterized. The extracellular mannanase (Mn428) was purified to homogeneity with 12.4 fold, specific activity of 2406.7 U/mg, and final recovery of 37.6 %. The purified ß-mannanase was found to be a monomeric protein with a molecular mass of approximately 35 kDa as analyzed by SDS-PAGE and zymography. The first N-terminal amino acid sequences of mannanase enzyme were HIRNGNHQLPTG. The optimal temperature and pH for enzyme were 60 °C and 12.5, respectively. The mannanase activities were significantly affected by the presence of metal ions, modulators, and detergents. Km and Vmax values of Mn428 were 1.01 ± 3.4 mg/mL and 5029 ± 85 µmol/min mg, respectively when different concentrations (0.6-10 mg/mL) of locust bean gum galactomannan were used as substrate. The substrate specificity of enzyme showed its highest specificity towards galactomannan which was further hydrolyzed to produce mannose, mannobiose, mannotriose, and a series of mannooligosaccharides. Mannooligosaccharides can be further converted to ethanol production, thus the purified ß-mannanase isolated from Streptomyces sp. CS428 was found to be attractive for biotechnological applications.

Why Perfluorocarbon nanoparticles encounter bottlenecks in clinical translation despite promising oxygen carriers?

Artificial Oxygen Carriers (AOCs) have emerged as ground-breaking biomedical solutions, showcasing tremendous potential for enhancing human health and saving lives. Perfluorocarbon (PFC)-based AOCs, in particular, have garnered significant interest among researchers, leading to numerous clinical trials since the 1980 s. However, despite decades of exploration, the success rate has remained notably limited. This comprehensive review article delves into the landscape of clinical trials involving PFC compounds, shedding light on the challenges and factors contributing to the lack of clinical success with PFC nanoparticles till date. By scrutinizing the existing trials, the article aims to uncover the underlying issues like pharmacological side effects of the PFC and the nanomaterials used for the designing, complex formulation strategy and poor clinical trial designs of the formulation. More over each generation of the PFC formulation were discussed with details for their failure in the clinical trials limitations that block the path of PFC-based AOCs' full potential. Furthermore, the review emphasizes a forward-looking approach by outlining the future pathways and strategies essential for achieving success in clinical trials. AOCs require advanced yet biocompatible single-componentformulations. The new trend might be a novel drug delivery technique, like gel emulsion or reverse PFC emulsion with fluoro surfactants. Most importantly, well-planned clinical trials may end in a success story.

The effect of oxygen supply using perfluorocarbon-based nanoemulsions on human hair growth.

Hair dermal papilla cells (hDPCs) play a crucial role in hair growth and regeneration, and their function is influenced by nutrient and oxygen supply. A microenvironment with significantly low oxygen (O2) levels, known as anoxic conditions (<0.2%) due to oxygen deficiency, hinders hDPC promotion and retards hair regrowth. Here, a nanoemulsion (NE) based on perfluorooctyl bromide (PFOB), a member of the perfluorocarbon family, is presented to provide a sustainable O2 supply and maintain physical stability in vitro. The PFOB-NE has been shown to continuously release oxygen for 36 h, increasing and maintaining the O2 concentration in the anoxic microenvironment of up to 0.8%. This sustainable O2 supply using PFOB-NE has promoted hDPC growth and also induced a complex cascade of effects. These effects encompass regulation via inhibiting lactate accumulation caused via oxygen deficiency, increasing lactate dehydrogenase activity, and promoting the expression of genes, such as the hypoxia-inducible factor 1 family and NADPH oxidase 4 under anoxic conditions. Sustained O2 supply is shown to enhance human hair organ elongation approximately four times compared to the control under anoxic conditions. In conclusion, the perfluorocarbon-based NE containing oxygen proves to be an important strategic tool for improving hair growth and alleviating hair loss.

Current perspectives of artificial oxygen carriers as red blood cell substitutes: a review of old to cutting-edge technologies using in vitro and in vivo assessments.

Background: Several circumstances such as accidents, surgery, traumatic hemorrhagic shock, and other causalities cause major blood loss. Allogenic blood transfusion can be resuscitative for such conditions; however, it has numerous ambivalent effects, including supply shortage, needs for more time, cost for blood grouping, the possibility of spreading an infection, and short shelf-life. Hypoxia or ischemia causes heart failure, neurological problems, and organ damage in many patients. To address this emergent medical need for resuscitation and to treat hypoxic conditions as well as to enhance oxygen transportation, researchers aspire to achieve a robust technology aimed to develop safe and feasible red blood cell substitutes for effective oxygen transport. Area covered: This review article provides an overview of the formulation, storage, shelf-life, clinical application, side effects, and current perspectives of artificial oxygen carriers (AOCs) as red blood cell substitutes. Moreover, the pre-clinical (in vitro and in vivo) assessments for the evaluation of the efficacy and safety of oxygen transport through AOCs are key considerations in this study. With the most significant technologies, hemoglobin- and perfluorocarbon-based oxygen carriers as well as other modern technologies, such as synthetically produced porphyrin-based AOCs and oxygen-carrying micro/nanobubbles, have also been elucidated. Expert opinion: Both hemoglobin- and perfluorocarbon-based oxygen carriers are significant, despite having the latter acting as safeguards; they are cost-effective, facile formulations which penetrate small blood vessels and remove arterial blockages due to their nano-size. They also show better biocompatibility and longer half-life circulation than other similar technologies.

A Review on Dry Eye Disease Treatment: Recent Progress, Diagnostics, and Future Perspectives.

Dry eye disease is a multifactorial disorder of the eye and tear film with potential damage to the ocular surface. Various treatment approaches for this disorder aim to alleviate disease symptoms and restore the normal ophthalmic environment. The most widely used dosage form is eye drops of different drugs with 5% bioavailability. The use of contact lenses to deliver drugs increases bioavailability by up to 50%. Cyclosporin A is a hydrophobic drug loaded onto contact lenses to treat dry eye disease with significant improvement. The tear is a source of vital biomarkers for various systemic and ocular disorders. Several biomarkers related to dry eye disease have been identified. Contact lens sensing technology has become sufficiently advanced to detect specific biomarkers and predict disease conditions accurately. This review focuses on dry eye disease treatment with cyclosporin A-loaded contact lenses, contact lens biosensors for ocular biomarkers of dry eye disease, and the possibility of integrating sensors in therapeutic contact lenses.

Cationic BODIPY Photosensitizers for Mitochondrion-Targeted Fluorescence Cell-Imaging and Photodynamic Therapy.

The straightforward synthesis of three cationic boron-dipyrromethene (BODIPY) derivatives and their mitochondria-targeting and photodynamic therapeutic (PDT) capabilities are reported. Two cancer cell lines (HeLa and MCF-7) were used to investigate the PDT activity of the dyes. Compared to their non-halogenated counterparts, halogenated BODIPY dyes exhibit lower fluorescence quantum yields and enable the efficient production of singlet oxygen species. Following LED light irradiation at 520 nm, the synthesized dyes displayed good PDT capabilities against the treated cancer cell lines, with low cytotoxicity in the dark. In addition, functionalization of the BODIPY backbone with a cationic ammonium moiety enhanced the hydrophilicity of the synthesized dyes and, consequently, their uptake by the cells. The results presented here collectively demonstrate the potential of cationic BODIPY-based dyes as therapeutic drugs for anticancer photodynamic therapy.

Paliperidone-Cation Exchange Resin Complexes of Different Particle Sizes for Controlled Release.

This study aimed to develop electrolyte complexes of paliperidone (PPD) with various particle sizes using cation-exchange resins (CERs) to enable controlled release (both immediate and sustained release). CERs of specific particle size ranges were obtained by sieving commercial products. PPD-CER complexes (PCCs) were prepared in an acidic solution of pH 1.2 and demonstrated a high binding efficiency (>99.0%). PCCs were prepared with CERs of various particle sizes (on average, 100, 150, and 400 µm) at the weight ratio of PPD to CER (1:2 and 1:4). Physicochemical characterization studies such as Fourier-transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy between PCCs (1:4) and physical mixtures confirmed PCC formation. In the drug release test, PPD alone experienced a complete drug release from PCC of >85% within 60 min and 120 min in pH 1.2 and pH 6.8 buffer solutions, respectively. Alternatively, PCC (1:4) prepared with CER (150 µm) formed spherical particles and showed an almost negligible release of PPD in pH 1.2 buffer (<10%, 2 h) while controlling the release in pH 6.8 buffer (>75%, 24 h). The release rate of PPD from PCCs was reduced with the increase in CER particle size and CER ratio. The PCCs explored in this study could be a promising technology for controlling the release of PPD in a variety of methods.

Development and Evaluation of Self-Microemulsifying Drug Delivery System for Improving Oral Absorption of Poorly Water-Soluble Olaparib.

The purpose of this study is to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS) to improve the oral absorption of poorly water-soluble olaparib. Through the solubility test of olaparib in various oils, surfactants and co-surfactants, pharmaceutical excipients were selected. Self-emulsifying regions were identified by mixing the selected materials at various ratios, and a pseudoternary phase diagram was constructed by synthesizing these results. The various physicochemical properties of microemulsion incorporating olaparib were confirmed by investigating the morphology, particle size, zeta potential, drug content and stability. In addition, the improved dissolution and absorption of olaparib were also confirmed through a dissolution test and a pharmacokinetic study. An optimal microemulsion was generated in the formulation of Capmul® MCM 10%, Labrasol® 80% and PEG 400 10%. The fabricated microemulsions were well-dispersed in aqueous solutions, and it was also confirmed that they were maintained well without any problems of physical or chemical stability. The dissolution profiles of olaparib were significantly improved compared to the value of powder. Associated with the high dissolutions of olaparib, the pharmacokinetic parameters were also greatly improved. Taken together with the results mentioned above, the microemulsion could be an effective tool as a formulation for olaparib and other similar drugs.

Exceptionally stable fluorous emulsions for the intravenous delivery of volatile general anesthetics.

BACKGROUND: IV delivery of volatile fluorinated anesthetics has a number of potential advantages when compared with the current inhalation method of administration. We reported previously that the IV delivery of sevoflurane can be achieved through an emulsion composed of a linear fluorinated diblock copolymer, a stabilizer, and the anesthetic. However, this original emulsion was subject to particle size growth that would limit its potential clinical utility. We hypothesized that the use of bulkier fluorous groups and smaller polyethylene glycol moieties in the polymer design would result in improved emulsion stability while maintaining anesthetic functionality. METHODS: The authors prepared emulsions incorporating sevoflurane, perfluorooctyl bromide as a stabilizing agent, and combinations of linear fluorinated diblock copolymer and a novel dibranched fluorinated diblock copolymer. Emulsion stability was assessed using dynamic light scattering. The ability of the emulsions to induce anesthesia was tested in vivo by administering them intravenously to 15 male Sprague-Dawley rats and measuring loss of the forepaw righting reflex. RESULTS: 20% (volume/volume) sevoflurane emulsions incorporating mixtures of dibranched and linear diblock copolymers had improved stability, with those containing an excess of the dibranched polymers displaying stability of particle size for more than 1 yr. The ED50s for loss of forepaw-righting reflex were all similar, and ranged between 0.55- 0.60 ml/kg body weight. CONCLUSIONS: Hemifluorinated dibranched polymers can be used to generate exceptionally stable sevoflurane nanoemulsions, as required of formulations intended for clinical use. IV delivery of the emulsion in rats resulted in induction of anesthesia with rapid onset and smooth and rapid recovery.

Encapsulation and release of Amphotericin B from an ABC triblock fluorous copolymer.

PURPOSE: PEG-phospholipid-based micelles have been successfully used for the solubilization of several hydrophobic drugs but generally lack sustained stability in blood. Our novel PEG-Fluorocarbon-DSPE polymers were designed to increase stability and improve time-release properties of drug-loaded micelles. METHODS: Novel ABC fluorous copolymers were synthesized, characterized, and used for encapsulation release of amphotericin B. FRET studies were used to study micelle stability. RESULTS: The micelles formed by the new polymers showed lower critical micelle concentrations and higher viscosity cores than those formed by the polymers lacking the fluorous block. FRET studies indicated that fluorocarbon-containing micelles had increased stability in presence of human serum. Physicochemical properties and in vitro release profile of micelles loaded with Amphotericin B (AmB) were studied. CONCLUSIONS: The effect of PEG length and fluorocarbon incorporation were investigated. The shorter hydrophilic PEG2K induced greater stability than PEG5K by decreasing the proportion of hydrophilic block of the polymer. The fluorocarbon placed between hydrophilic and hydrophobic block formed a fluorous shell contributing to the enhanced thermodynamic stability of micelles and to the drug sustained release. Polymer mPEG2K-F(10)-DSPE, bearing both a fluorocarbon block and a shorter mPEG, showed the greatest stability and the longest half-life for AmB release.

Development of chitosan-based ondansetron buccal delivery system for the treatment of emesis.

BACKGROUND: For the buccal drug delivery, chitosan (CS) can be used to improve drug absorption and reduce application frequency and drug amount. The aim of this study is to develop and evaluate mucoadhesive ondansetron buccal films for the treatment of emesis using CS as a mucoadhesive polymer. METHODS: The film prepared by solvent casting method was comprised of ondansetron (approximately 65 µg)-loaded mucoadhesive gels containing 1, 2 or 3% CS and impermeable backing layer. Rheological property of the gels, physiochemical properties of the films (weight, thickness, drug content, swelling ratio, adhesion time and mucoadhesive force) and in vitro ondansetron release profile from the films were determined to evaluate the formulation. The films containing 3% CS (diameter: 0.5 cm; thickness: 170 µm) was selected as the novel formulation, and were used for the in vivo study. Comparative pharmacokinetic studies of ondansetron with this film and oral solution were performed at the same dose in hamsters. RESULTS: The mean values of T(max) and C(max) of the film and oral solution were similar. However, the half-life, mean residence time and AUC(0-24 h) of the film were about 1.7, 1.4 and 2.0-fold higher than those of the oral solution, respectively. The film showed enhanced bioavailability and prolonged efficacy compared to the oral solution. CONCLUSIONS: The mucoadhesive ondansetron buccal film may be a potential alternative to the marketed oral formulation, parenterals and solid suppositories with better patient compliance and higher bioavailability for the treatment of emesis.