Evaluating Novel Agarose-Based Buccal Gels Scaffold: Mucoadhesive and Pharmacokinetic Profiling in Healthy Volunteers.

Agarose (AG) forms hydrocolloid in hot water and possesses a noteworthy gel strength. However, no reasonable scientific work on investigating the mucoadhesive character of AG has been reported. Therefore, the current study was designed to develop AG and carbopol (CP) based buccal gel scaffold for simultaneous release of benzocaine (BZN) and tibezonium iodide (TIB). Gels' scaffold formulations (F1−F12) were prepared with varied concentrations (0.5−1.25% w/v) of AG and CP alone or their blends (AG-CP) using homogenization technique. The prepared formulations were characterized for solid-state, physicochemical, in vitro, ex vivo, and in vivo mucoadhesive studies in healthy volunteers. The results showed that mucoadhesive property of AG was concentration dependent but improved by incorporating CP in the scaffolds. The ex vivo mucoadhesive time reached >36 h when AG was used alone or blended with CP at 1% w/v concentration or above. The optimized formulation (F10) depicted >98% drugs release within 8 h and was also storage stable up to six months. The salivary concentration of BZN and TIB from formulation F10 yielded a Cmax value of 9.97 and 8.69 µg/mL at 2 and 6 h (tmax), respectively. In addition, the FTIR, PXRD, and DSC results confirmed the presence of no unwanted interaction among the ingredients. Importantly, the mucoadhesive study performed on healthy volunteers did not provoke any signs of inflammation, pain, or swelling. Clearly, it was found from the results that AG-CP scaffold provided better mucoadhesive properties in comparison to pure AG or CP. Conclusively, the developed AG based mucoadhesive drug delivery system could be considered a potential alternative for delivering drugs through the mucoadhesive buccal route.

Development of Chitosan-Based Nanoemulsion Gel Containing Microbial Secondary Metabolite with Effective Antifungal Activity: In vitro and in vivo Characterizations.

PURPOSE: Microbial resistance to antibiotics is one of the most important public health concerns of the 21st century. We isolated, purified, and structurally elucidated antifungal secondary metabolites from red soil microbes and encapsulated them into chitosan (CS)-based nanoemulsion (NE) gel (NEG). METHODS: Three compounds were isolated and purified of which only one compound (Pure 2) showed potent antifungal activity (MFC: 8-132 µg/mL), which was also significantly (P<0.05) more efficient than fluconazole (MFC: 32-132 µg/mL). Pure 2 was structurally elucidated using 1D- and 2D-NMR before its incorporation into NEG. The formulations were prepared by high-speed homogenization technique. Physicochemical and pharmacological characterizations of formulations (ie, droplet size, PDI, zeta potential, drug content, viscosity, SEM, FTIR, spreadability, in vitro drug release, ex vivo permeation, in vitro antifungal and in vivo antifungal activities) were assessed. RESULTS: NMR analyses identified the compound as a derivative of phthalic acid ester (PAE). The optimized formulations displayed a droplet size <100 nm, -ve zeta potential, and PDI <0.45. The drug content was within the official limit of pharmacopeia (ie, 100±10%). Insignificant changes (P>0.05) in the viscosity of the formulations stored were observed. The morphology of the formulations indicated mesh-like structure. The FTIR study indicated that there were no interactions between the drug and other ingredients of the formulations. Optimum spreadability was observed in all formulations. NEG released 75.3±1.12% of Pure 2 after 12 hrs while NE released 85.33±1.88% of the compound. The skin permeation of F2 (71.15±1.28%) was significantly different (P<0.05) from F3 (81.80±1.91%) in rabbits. Complete and apparently safe recovery from the fungal infection was achieved in rabbits treated topically with Pure 2-loaded NEGs. CONCLUSION: Hence, the NEG-loaded PAE isolated from Pseudomonas fluorescens represents a possible alternative for the treatment of fungal infections as compared to available therapies.

Optimization of carvedilol solid lipid nanoparticles: An approach to control the release and enhance the oral bioavailability on rabbits.

Solid lipid nanoparticles (SLNs) are prospective carriers for oral delivery of poorly soluble drugs with low bioavailability. Therefore, the study aimed at developing carvedilol (CVD) in SLNs to control its release and enhance its bioavailability in the management of hypertension, and cardiac diseases. Box-Behnken design (BBD) was applied to optimize the variables affecting the quality of CVD-SLNs which prepared by homogenization-ultrasonication technique. The concentrations of Percirol (X1), Gelucire (X2), and stearylamine (X3) were chosen as the crucial independent variables. The dependent variables were estimated and analyzed by Statgraphics software to achieve the optimum characteristics of the developed SLNs. The optimized SLNs was evaluated in vitro and in vivo for pharmacokinetic parameters on male New Zealand white rabbits. The results of this study revealed that the CVD-SLNs have a colloidal size of 31.3 nm with zeta potential of 24.25 mV indicating good stability and 91.43% entrapment efficiency. The in vitro release of CVD from the SLNs was best fitted to Hixon-Crowell model that describes the release from the particles with uniform size. The in vivo pharmacokinetics results indicated the prolongation in the mean residence time of CVD to 23 h when delivered in SLNs and its oral bioavailability enhanced by more than 2-folds.

Quality by design approach to optimize the formulation variables influencing the characteristics of biodegradable intramuscular in-situ gel loaded with alendronate sodium for osteoporosis.

There are many challenges facing the use of alendronate sodium for the treatment of osteoporosis such as low bioavailability of 0.6% and oesophageal ulceration with bleeding. Due to the aforementioned limitation, the main objective of this research is to utilize a statistical experimental design in the formulation and optimization of alendronate in the form of controlled release biodegradable intramuscular in-situ gel. A Box-Behnken experimental design employing Statgraphics® software was used to develop an optimized in-situ gel formulation and to estimate the effects of Poly-DL-lactide-coglycolide as a primary polymer, the copolymer polycaprolactone, and lipid surfactant capryol 90. Every system was evaluated for gellation character, and in vitro release. As a novel technique for evaluation of the in-situ gel, in-vivo biodegradability rate was estimated in rats. Pharmacokinetic parameters were assessed in rabbits. The results indicated a significant effect of the copolymer and lipid surfactant on initial burst, and a significant effect of the primary and copolymer on drug percentage released. The optimum formulation showed a 5% initial burst, an in-vivo biodegradability rate estimated at 8% every seven days in rats, and the pharmacokinetic evaluation revealed that alendronate sodium mean residence time extended to 102 days in rabbits. In conclusion, the optimum biodegradable intramuscular in-situ gel formulations is a promising approach for providing higher bioavailability, extended release for more than three months, with elimination of esophageal side effects.

Fabrication and evaluation of Phytomenadione as a nanostructure lipid carrier for enhancement of bioavailability.

Owing to its limited aqueous solubility, Phytomenadione (vitamin K) undergoes a low bioavailability (50%) with a large inter-individual variability after oral administration. Therefore, the aim of this work was to incorporate vitamin K into nanostructure lipid carrier systems to improve its aqueous solubility and bioavailability. Phytomenadione was used as a liquid lipid; Precirol ATO5, and Compritol ATO were used as solid lipids; Labrasol and Cremophore EL as water soluble surfactants; Capryol 90 and Lauroglycol as lipid soluble surfactants. Eight formulas were prepared and characterized for their particle sizes, zeta potential, entrapment efficiencies, and drug release. Those formulas had particle sizes ranging from 25.4 to 68.3 nm. The best formula, consisting of 15% Phytomenadione, 45% Precirol ATO5, 30% Cremophore EL, and 10% Lauroglycol 90, was selected for stability study and characterized by the techniques mentioned above and scanning electron microscopy. It had the highest drug loading and an acceptable in vitro release profile (94.54% within 30 min). This formula was also chemically and physically stable, and it recorded a relative bioavailability of 645.5% in rabbits compared to the commercial conventional tablet. This formula could be a promising carrier regarding its ease of preparation, dosage form versatility and enhanced bioavailability.

Alendronate Sodium as Enteric Coated Solid Lipid Nanoparticles; Preparation, Optimization, and In Vivo Evaluation to Enhance Its Oral Bioavailability.

Treatment of osteoporosis with alendronate sodium has several challenges. The first challenge is the low bioavailability. The second main challenge is side effects, which include oesophageal ulceration. The aim of this research was to reformulate alendronate sodium as enteric coated solid lipid nanoparticles in order to enhance its bioavailability, and preventing the free alendronate sodium from coming into direct contact with the gastrointestinal mucosa, and thereby reducing the possibility of side effects. Enteric coated solid lipid nanoparticles were prepared according to the Box-Behnken design employing Design expert® software, and characterized for size, morphology, and entrapment efficiency. The optimized formula was coated with an Eudragit S100 and evaluated for drug release in acidic and basic media, stability studies and pharmacokinetic evaluations on rabbits. The results indicated that, using Derringer's desirability functional tool for optimization, the highest entrapment efficiency value of 74.3% and the smallest size value of 98 nm were predicted under optimum conditions with a desirability value of 0.917. The optimized nanoparticles released alendronate sodium only at an alkaline pH. The pharmacokinetic evaluation revealed that alendronate sodium bioavailability was enhanced by more than 7.4-fold in rabbits. In conclusion, enteric coated solid lipid nanoparticles is a promising formula for the delivery of alendronate sodium, eliminating its oesophageal side effects and enhancing its bioavailability.

Miconazole-loaded solid lipid nanoparticles: formulation and evaluation of a novel formula with high bioavailability and antifungal activity.

BACKGROUND AND OBJECTIVE: Miconazole is a broad-spectrum antifungal drug that has poor aqueous solubility (<1 µg/mL); as a result, a reduction in its therapeutic efficacy has been reported. The aim of this study was to formulate and evaluate miconazole-loaded solid lipid nanoparticles (MN-SLNs) for oral administration to find an innovative way to alleviate the disadvantages associated with commercially available capsules. METHODS: MN-SLNs were prepared by hot homogenization/ultrasonication. The solubility of miconazole in different solid lipids was measured. The effect of process variables, such as surfactant types, homogenization and ultrasonication times, and the charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release, antifungal activity against Candida albicans, and in vivo pharmacokinetics were studied in rabbits. RESULTS: The MN-SLN, consisting of 1.5% miconazole, 2% Precirol ATO5, 2.5% Cremophor RH40, 0.5% Lecinol, and 0.1% Dicetylphosphate, had an average diameter of 23 nm with a 90.2% entrapment efficiency. Furthermore, the formulation of MN-SLNs enhanced the antifungal activity compared with miconazole capsules. An in vivo pharmacokinetic study revealed that the bioavailability was enhanced by >2.5-fold. CONCLUSION: MN-SLN was more efficient in the treatment of candidiasis with enhanced oral bioavailability and could be a promising carrier for the oral delivery of miconazole.

Optimized sildenafil citrate fast orodissolvable film: a promising formula for overcoming the barriers hindering erectile dysfunction treatment.

Sildenafil citrate, a drug used to treat erectile dysfunction, is available in tablet form but has three major problems. First, the drug displays poor aqueous solubility, which delays its onset of action. Second, the drug undergoes extensive first-pass metabolism, resulting in a low (40%) bioavailability. Third, the gastrointestinal effects of sildenafil citrate include dyspepsia and a burning sensation. The objective of this study was to prepare sildenafil citrate using a fast orodissolvable film (ODF) containing the drug in a solid dispersion (SD) to mitigate the abovementioned problems. The solubility of sildenafil citrate in ß-cyclodextrin derivatives was estimated, and SDs were prepared and characterized. To develop an ODF that disintegrates rapidly and releases the maximum amount of sildenafil citrate, a 3(3) Box-Behnken experimental design was used to estimate the effects of different concentrations of film forming polymer (X1), the film modifier (X2), and the plasticizer (X3) on the responses, i.e. the disintegration time (Y1) and the amount of drug released (Y2). Pharmacokinetic studies with the optimized (ODF) were conducted on human volunteers. SD prepared using hydroxybutyl-ß-cyclodextrin enhanced the solubility of sildenafil citrate by more than eightfold. The Y1 for the optimized ODF was 89 seconds, and the Y2 was 86%; this formula also exhibited a rapid onset of action, and its bioavailability was enhanced by 2.25-fold compared with that of the marketed tablet. The ODF is a promising formulation for sildenafil citrate that results in higher solubility, a rapid onset of action, and enhanced systemic bioavailability.

Depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein-2: preparation, characterization, and in vivo evaluation.

OBJECTIVE: The aim of this study is to utilize the biocompatibility characteristics of biodegradable polymers, viz, poly lactide-co-glycolide (PLGA) and polycaprolactone (PCL), to prepare sustained-release injectable nanoparticles (NPs) of bone morphogenetic protein-2 (BMP-2) for the repair of alveolar bone defects in rabbits. The influence of formulation parameters on the functional characteristics of the prepared NPs was studied to develop a new noninvasive injectable recombinant human BMP-2 (rhBMP-2) containing grafting material for the repair of alveolar bone clefts. MATERIALS AND METHODS: BMP-2 NPs were prepared using a water-in-oil-in-water double-emulsion solvent evaporation/extraction method. The influence of molar ratio of PLGA to PCL on a suitable particle size, encapsulation efficiency, and sustained drug release was studied. Critical size alveolar defects were created in the maxilla of 24 New Zealand rabbits divided into three groups, one of them treated with 5 µg/kg of rhBMP-2 NP formulations. RESULTS: The results found that NPs formula prepared using blend of PLGA and PCL in 4:2 (w/w) ratio showed the best sustained-release pattern with lower initial burst, and showed up to 62.7% yield, 64.5% encapsulation efficiency, 127 nm size, and more than 90% in vitro release. So, this formula was selected for scanning electron microscope examination and in vivo evaluation. Histomorphometric analysis showed 78% trabecular bone fill, mostly mature bone in the defects treated with rhBMP-2 in NPs within 6 weeks. CONCLUSION: The prepared NPs prolonged the release and the residence time of rhBMP-2 in rabbits, which led to the formation of adequate bone in critical size alveolar bone defects in 6 weeks. This noninvasive method has application for the primary restoration of alveolar bone defects.

Solid lipid nanoparticles loaded with iron to overcome barriers for treatment of iron deficiency anemia.

According to the World Health Organization, 46% of the world's children suffer from anemia, which is usually treated with iron supplements such as ferrous sulfate. The aim of this study was to prepare iron as solid lipid nanoparticles, in order to find an innovative way for alleviating the disadvantages associated with commercially available tablets. These limitations include adverse effects on the digestive system resulting in constipation and blood in the stool. The second drawback is the high variability in the absorption of iron and thus in its bioavailability. Iron solid lipid nanoparticles (Fe-SLNs) were prepared by hot homogenization/ultrasonication. Solubility of ferrous sulfate in different solid lipids was measured, and effects of process variables such as the surfactant type and concentration, homogenization and ultrasonication times, and charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release and in vivo pharmacokinetics were studied in rabbits. Results indicated that Fe-SLNs consisted of 3% Compritol 888 ATO, 1% Lecithin, 3% Poloxamer 188, and 0.2% dicetylphosphate, with an average particle size of 25 nm with 92.3% entrapment efficiency. In vivo pharmacokinetic study revealed more than fourfold enhanced bioavailability. In conclusion, Fe-SLNs could be a promising carrier for iron with enhanced oral bioavailability.

Soy polysaccharide as a novel superdisintegrant in sildenafil citrate sublingual tablets: preparation, characterization, and in vivo evaluation.

Sildenafil citrate (SC), a drug used to treat erectile dysfunction, is available in tablet form but has three major problems. First, the drug displays inadequate aqueous solubility, which delays the onset of its action. Second, the drug undergoes extensive first-pass metabolism, resulting in a low (40%) bioavailability. Third, the gastrointestinal effects of SC include dyspepsia and a burning sensation. The aim of this research was to prepare SC as a sublingual tablet utilizing soy polysaccharide as novel superdisintegrant to mitigate the abovementioned problems. The solubility of SC in various hydrophilic carrier solutions was estimated in order to prepare the drug as a coprecipitate. Sublingual tablets were prepared and evaluated for hardness, friability, drug content, wetting time, water absorption ratio, in vitro dispersion time, dissolution rate, and stability study. The pharmacokinetic study of the tablets was carried out on healthy volunteers. The results indicated that the co-precipitation of SC with polyvinylpyrollidone K30 enhanced the solubility of SC by more than eight folds. The tablet contained 8% soy polysaccharide as a superdisintegrant and provided a wetting time of 25 seconds, and in vitro dispersion times of 55 seconds. The drug release was found to be 95.6%. The prepared SC sublingual tablet also exhibited a rapid onset of action, and its bioavailability was enhanced 1.68-fold compared with that of the marketed tablets. It can be concluded that SC sublingual tablet is a promising formulation that results in higher solubility, faster dispersion and onset of action, higher release rate, and higher systemic bioavailability.

Intranasal in situ gel loaded with saquinavir mesylate nanosized microemulsion: preparation, characterization, and in vivo evaluation.

Saquinavir mesylate (SM) is a protease inhibitor with activity against human immunodeficiency virus type 1 (HIV-1) and is available in tablet form, which has three major problems. First, the drug undergoes extensive first pass metabolism. Second, the drug has a poor aqueous solubility. And third, it has low GIT permeability and absorption. These constrains lead to decrease oral bioavailability (4% only) and administration of large doses which increase the incidence of occurrence of the side effects. The aim of this research was to utilize nanotechnology to formulate (SM) into a nasal in situ nanosized microemulsion gel (NEG) to provide a solution for the previously mentioned problems. The solubility of (SM) in various oils, surfactants, and cosurfactants was estimated. Pseudo-ternary phase diagrams were developed and various nanosized microemulsion (NE) were prepared, and subjected to characterization, stability study, and droplet size measurements. Gellan gum was used as an in situ gelling agent. The gel strength, critical ionic concentration, gelation characteristics, in vitro release, and ex vivo nasal permeation were determined. The pharmacokinetic study was carried out in rabbits. Stable NEs were successfully developed with a droplet size range of 25-61 nm. A NEG composed of 17.5% Labrafac PG, 33% Labrasol, and 11% Transcutol HP successfully provided the maximum in vitro and ex vivo permeation, and enhanced the bioavailability in the rabbits by 12-fold when compared with the marketed tablets. It can be concluded that the nasal NEG is a promising novel formula for (SM) that has higher nasal tissue permeability and enhanced systemic bioavailability.

The formulation of a nasal nanoemulsion zaleplon in situ gel for the treatment of insomnia.

BACKGROUND: Zaleplon is a drug used for the treatment of insomnia and is available in tablet form; however, it has two major problems. First, the drug undergoes extensive first pass metabolism, resulting in only 30% bioavailability, and second, the drug has a poor aqueous solubility, which delays the onset of action. OBJECTIVE: The objective of this study is to utilise nanotechnology to formulate zaleplon into a nasal in situ nanoemulsion gel (NEG) to provide a solution for the previously mentioned problems. METHODS: The solubility of zaleplon in various oils, surfactants and co-surfactants was estimated. Pseudo-ternary phase diagrams were developed and various nanoemulsion (NE) formulations were prepared; these formulations were subjected to visual characterisation, thermodynamic stability study and droplet size and conductivity measurements. Carbopol 934 was used as an in situ gelling agent. The gel strength, pH, gelation time, in vitro release and ex vivo nasal permeation were determined. The pharmacokinetic study of the NEG was carried out in rabbits. RESULTS: Stable NEs were successfully developed with a droplet size range of 35 to 73 nm. A NEG composed of 15% Miglyol, 30% Labrasol and 10% PEG 200 successfully provided the maximum in vitro and ex vivo permeation and enhanced the bioavailability in the rabbits by eightfold, when compared with the marketed tablets. CONCLUSION: The nasal NEG is a promising novel formula for zaleplon that has higher nasal tissue permeability and enhanced systemic bioavailability.

Enteric-coated alendronate sodium nanoliposomes: a novel formula to overcome barriers for the treatment of osteoporosis.

BACKGROUND AND OBJECTIVES: Alendronate sodium (ALS) is the most common drug used for the treatment of osteoporosis. The challenges facing ALS use include: very poor oral bioavailability (0.6%), esophageal ulcers, and complicated instructions for its use. The objective of this research is to utilize nanotechnology to formulate ALS into enteric-coated nanoliposomes (NLS) to overcome the previously mentioned drawbacks. METHODS: NLS were prepared with lipid components of phosphatidylcholine (PC), cholesterol (CH), and lecithin (Lec) in ratios 4:1:1, 4:2:1, 4:3:1, and 4:4:1, respectively. Formulas that showed the highest entrapment efficiency were prepared either alone or mixed with positive and negative charge-inducing agents and coated with Eudragit L100. Eudragit-coated NLS (EuC-NLS) were evaluated for particle size, zeta potential, morphological examination, and drug release in pH 1.2 and pH 7.4 media. The pharmacokinetic study was carried out in rabbits. RESULTS: Spherical NLS were successfully developed with a mean size range from 70 to 150 nm. EuC-NLS with PC:CH:Lec:dicetyl phosphate (4:3:1:1) successfully resist the release of ALS in acidic environments and enhanced the bioavailability in rabbits 12-fold compared with the marketed tablets. CONCLUSIONS: EuC-NLS is a promising novel formula for ALS with higher bioavailability and a lower dose, avoiding the side effects of esophageal ulceration.

Ciprofloxacin as ocular liposomal hydrogel.

The purpose of this study was to prepare and characterize an ocular effective prolonged-release liposomal hydrogel formulation containing ciprofloxacin. Reverse-phase evaporation was used for preparation of liposomes consisting of soybean phosphatidylcholine (PC) and cholesterol (CH). The effect of PC/CH molar ratio on the percentage drug encapsulation was investigated. The effect of additives such as stearylamine (SA) or dicetyl phosphate (DP) as positive and negative charge inducers, respectively, were studied. Morphology, mean size, encapsulation efficiency, and in vitro release of ciprofloxacin from liposomes were evaluated. For hydrogel preparation, Carbopol 940 was applied. In vitro transcorneal permeation through excised albino rabbit cornea was also determined. Optimal encapsulation efficiency of 73.04 +/- 3.06% was obtained from liposomes formulated with PC/CH at molar ratio of 5:3 and by increasing CH content above this limit, the encapsulation decreased. Positively charged liposomes showed superior entrapment efficiency (82.01 +/- 0.52) over the negatively charged and the neutral liposomes. Hydrogel containing liposomes with lipid content PC, CH, and SA in molar ratio 5:3:1, respectively, showed the best release and transcorneal permeation with the percentage permeation of 30.6%. These results suggest that the degree of encapsulation of ciprofloxacin into liposomes and prolonged in vitro release depend on composition of the vesicles. In addition, the polymer hydrogel used in preparation ensure steady and prolonged transcorneal permeation. In conclusion, ciprofloxacin liposomal hydrogel is a suitable delivery system for improving the ocular bioavailability of ciprofloxacin.

Optimization of gatifloxacin liposomal hydrogel for enhanced transcorneal permeation.

The aim of this study was to prepare and characterize a topically effective prolonged-release ophthalmic gatifloxacin liposomal hydrogel formulation. Reverse-phase evaporation was used for the preparation of liposomes consisting of phosphatidylcholine (PC) and cholesterol (CH). The effect of PC:CH molar ratio on the percentage of drug encapsulated was investigated. The effect of additives, such as stearylamine (SA) or dicetyl phosphate (DP), as positive and negative charge inducers, respectively, was studied. Morphology, mean size, encapsulation efficiency, and in vitro release of gatifloxacin from liposomes were evaluated. For hydrogel preparation, carbopol 940 was applied. In vitro transcorneal permeation through excised albino rabbit cornea was also determined. Optimal encapsulation efficiency was found at the 5:3 PC:CH molar ratio; by increasing CH content above this limit, the encapsulation efficiency decreased. Positively charged liposomes showed superior entrapment efficiency over other liposomes. Hydrogel-containing liposomes with lipid content PC, CH, and SA in a molar ratio of 5:3:1, respectively, showed best release and transcorneal permeation. These results suggest that the encapsulation of gatifloxacin into liposomes prolonged the in vitro release, depending on composition of the vesicles. In addition, the polymer hydrogel used in the preparation ensured steady, prolonged transcorneal permeation. In conclusion, gatifloxacin liposomal hydrogel is a suitable delivery system for the improvement of the ocular bioavailability of gatifloxacin.

Preparation and evaluation of thermosensitive liposomal hydrogel for enhanced transcorneal permeation of ofloxacin.

Ofloxacin, available as ophthalmic solution, has two major problems: first, it needs frequent administration every 4 hours or even every 1 hour to treat severe eye infection; second, there is formation of white crystalline deposit on cornea due to its pH-dependent solubility, which is very low at pH of corneal fluid. In order to provide a solution to previous problems, ofloxacin in this study is prepared as topically effective in situ thermosensitive prolonged release liposomal hydrogel. Two preparation procedures were carried out, leading to the formation of multilamellar vesicles (MLVs) and reverse-phase evaporation vesicles (REVs) at pH 7.4. Effects of method of preparation, lipid content, and charge inducers on encapsulation efficiency were studied. For the preparation of in situ thermosensitive hydrogel, chitosan/beta-glycerophosphate system was synthesized and used as carrier for ofloxacin liposomes. The effect of addition of liposomes on gelation temperature, gelation time, and rheological behaviors of the hydrogel were evaluated. In vitro transcorneal permeation was also determined. MLVs entrapped greater amount of ofloxacin than REVs liposomes at pH 7.4; drug loading was increased by including charge-inducing agent and by increasing cholesterol content until a certain limit. The gelation time was decreased by the addition of liposomes into the hydrogel. The prepared liposomal hydrogel enhances the transcorneal permeation sevenfold more than the aqueous solution. These results suggested that the in situ thermosensitive ofloxacin liposomal hydrogel ensures steady and prolonged transcorneal permeation, which improves the ocular bioavailability, minimizes the need for frequent administration, and decreases the ocular side effect of ofloxacin.