Delivery of cefotaxime to the brain via intranasal administration

The purpose of this study was to investigate the plausibility of delivery of cefotaxime to the brain via intranasal administration. In vitro permeation studies were carried out using Franz diffusion cells, and the effect of different concentrations of chitosan (0.1% w/v and 0.25% w/v) on drug permeation across the bovine olfactory mucosa was determined. Samples were collected from the receiver compartment at different time points and analyzed using HPLC. The amount of cefotaxime that permeated across the olfactory mucosa when 0.25% w/v of chitosan was used as a permeation enhancer was ~1.5- and ~2-fold higher at the end of the first hour and second hour, respectively, over control (29.56?±?6.18 µg/cm²). There was no significant enhancement in drug permeation when 0.1% w/v chitosan was used as the permeation enhancer. Pharmacokinetic studies were carried out using Sprague-Dawley rats. Cefotaxime solution with 0.25% w/v chitosan (40?mg/kg) was administered intravenously (i.v.) to rats in groups 1 and 3 and intranasally to those in group 2 and 4. The time course of drug in the brain was investigated by performing microdialysis in rats of groups 1 and 2. Blood samples were withdrawn from rats in groups 3 and 4, and cefotaxime in plasma was analyzed using HPLC after extraction with a hydrochloric acid–chloroform:1-pentanol (3:1) and phosphate buffer solvent system. Pharmacokinetic parameters were calculated using the trapezoidal rule. The results imply that the drug levels attained in the brain following i.v. and intranasal administrations were comparable. These results suggest that intranasal administration of cefotaxime could be a potential method of delivering antibacterial agents because of it being noninvasive and patient compliant.     

Basil oil is a promising skin penetration enhancer for transdermal delivery of labetolol hydrochloride

The present work investigates effectiveness of basil oil, a volatile oil containing alcoholic terpenes, as a potential penetration enhancer for improved skin permeation of labetolol hydrochloride (LHCl) with reference to camphor, geraniol, thymol, and clove oil. Saturation solubilities of LHCl were determined in water, vehicle (ethanol:water, 60:40 v/v) and vehicle containing 5% w/v terpenes. Comparable (P > 0.05) saturation solubilities were found suggesting an insignificant increase in LHCl flux across rat skin on account of thermodynamic activity. Permeation of LHCl in vehicle per se and in presence of 5% w/v enhancer was investigated by performing in vitro rat abdominal skin permeation studies using a side-by-side glass diffusion cell. Various parameters viz. steady state flux, permeability coefficient, lag time, partition coefficient, diffusion coefficient, and enhancement ratios (ER) were calculated from the permeation data. Basil oil produced the maximum enhancement (ER = 46.52) over neat vehicle, among all enhancers. Activation energies for LHCl permeation in water, vehicle per se and in presence of 5% w/v basil oil were found to be 23.16, 18.71, and 10.98 kcal/mole, respectively. Lowering of activation energy in presence of basil oil suggests creation of new polar pathways in the skin for enhanced permeation of LHCl. Basil oil is proposed as a promising penetration enhancer for improved transdermal drug delivery of labetolol.     

Basil Oil is a Promising Skin Penetration Enhancer for Transdermal Delivery of Labetolol Hydrochloride

Thepresent work investigates effectiveness of basil oil, a volatile oil containing alcoholic terpenes, as a potential penetration enhancer for improved skin permeation of labetolol hydrochloride (LHCl) with reference to camphor, geraniol, thymol, and clove oil. Saturation solubilities of LHCl were determined in water, vehicle (ethanol:water, 60:40 v/v) and vehicle containing 5% w/v terpenes. Comparable (P > 0.05) saturation solubilities were found suggesting an insignificant increase in LHCl flux across rat skin on account of thermodynamic activity. Permeation of LHCl in vehicle per se and in presence of 5% w/v enhancer was investigated by performing in vitro rat abdominal skin permeation studies using a side-by-side glass diffusion cell. Various parameters viz. steady state flux, permeability coefficient, lag time, partition coefficient, diffusion coefficient, and enhancement ratios (ER) were calculated from the permeation data. Basil oil produced the maximum enhancement (ER?=?46.52) over neat vehicle, among all enhancers. Activation energies for LHCl permeation in water, vehicle per se and in presence of 5% w/v basil oil were found to be 23.16, 18.71, and 10.98 kcal/mole, respectively. Lowering of activation energy in presence of basil oil suggests creation of new polar pathways in the skin for enhanced permeation of LHCl. Basil oil is proposed as a promising penetration enhancer for improved transdermal drug delivery of labetolol.     

Heparin decreases permeability of pig urinary bladder wall preliminarily enhanced by chitosan

Chitosan significantly increases the permeability of the isolated pig urinary bladder wall by causing urothelial desquamation, the extent of which depends also on the concentration of the polymer. By desquamation permeability barriers of the urothelium are removed. To gain additional insight into the mechanism by which chitosan acts an absorption enhancer into urinary bladder mucosa, we evaluated the influence of a polysaccharide heparin on the permeability of isolated pig urinary bladder wall preliminarily treated with chitosan. Moreover, we aimed to establish whether the effect of heparin depends on its concentration and on the degree of urothelial desquamation caused by chitosan. In the permeability studies performed by the use of diffusion cells, transport of a model drug, pipemidic acid, into the isolated pig urinary bladder wall was determined. Heparin did not have a significant effect on the permeability of the intact urothelium. When applied to the urinary bladder wall, whose permeability was preliminarily enhanced by 0.005% or 0.001% w/v chitosan, heparin decreased the permeation of pipemidic acid into the bladder wall to a level not significantly different from the intact tissue. However, the effect of heparin was not significant at the highest concentration of chitosan tested, where the damage to the urothelium was much more intense compared with that found at lower concentrations of the polymer. The formation of complexes between pipemidic acid and heparin cannot be excluded completely, but it seems that they are not the main reason for the decreased permeation of pipemidic acid in the presence of heparin. By application on the urothelium, damaged by chitosan, heparin is supposed to form a layer on the surface of the urothelium that prevents the transport of the model drug into the bladder wall. In this way heparin probably restores the impermeability properties of the urinary bladder wall to a degree dependent on the urothelial damage.     

Spray drying formulation of albendazole microspheres by experimental design. In vitro–in vivo studies

Both an experimental design and optimization techniques were carried out for the development of chitosan–pectin–carboxymethylcellulose microspheres to improve the oral absorption of albendazole as a model drug. The effect of three different factors (chitosan, pectin and carboxy methyl cellulose concentrations) was studied on five responses: yield, morphology, dissolution rate at 30 and 60?min, and encapsulation efficiency of the microspheres. During the screening phase, the factors were evaluated in order to identify those which exert a significant effect. Simultaneous multiple response optimizations were then used to find out experimental conditions where the system shows the most adequate results. The optimal conditions were found to be: chitosan concentration, 1.00% w/v, pectin concentration 0.10% w/v and carboxymethylcellulose concentration 0.20% w/v. The bioavailability of the loaded drug in the optimized microspheres was evaluated in Wistar rats which showed an area under curve (AUC) almost 10 times higher than the pure drug.     

Comparison of Skin Permeation of Dideoxynucleoside-Type Anti-HIV Drugs: Alone Versus Combination

The effects of vehicles and skin permeation enhancer on the skin permeation of dideoxynucleoside-type anti-HN drugs, Zalcitabine (DDC), Didanosine (DDI), and Zidovudine (AZT), alone and in combination, were compared using hairless rat and human cadaver skins. Each drug alone or a combination of three drugs was added to various compositions of ethanol/water or ethanol/tricaprylin cosolvent system to saturation, and in vitro skin permeation studies were conducted using Valia-Chien skin permeation cells. In both ethanol/water and ethanol/tricaprylin systems, the hairless rat skin permeation rates achieved by each drug alone and three drugs in combination were not significantly different. Addition of oleic acid [1.0% (v/v) for each drug alone and 5.0% (v/v) for drug combination] in ethanol/tricaprylin (50:50) could not significantly enhance the skin permeation of these drugs. In hairless rat skin permeation of each drug alone, the permeation rates of all three drugs were dramatically enhanced with the addition of oleic acid in ethanol/water (60:40) cosolvent system and reached plateau level with oleic acid as low as 0.3% (v/v). However, in the case of drug combination, the enhancement of skin permeation rates of these drugs with the addition of oleic acid in ethanol/water (80:20) cosolvent system was not as high as that observed for each drug alone, and plateau level was not observed even at 5.0% (v/v) of oleic acid. Human cadaver skin permeation rates of each drug alone saturated in ethanol/ water (60:40) cosolvent system containing 1.0% (v/v) of oleic acid were 3-4 times lower than those of hairless rat skin. However, in skin permeation of three drugs in combination, saturated in ethanol/water (80:20) cosolvent system containing 5.0% (v/v) of oleic acid, human cadaver skin permeation rates of DDC and DDI were slightly lower than those of hairless rat skin, and there was no significant difference between the two skins for AZT. These results show that mutual skin permeation-enhancing effects of oleic acid and an ethanol/water cosolvent system Made the transdermal delivery of anti-HIV drugs, alone and in combination, feasible.     

Comparison of Skin Permeation of Dideoxynucleoside-Type Anti-HIV Drugs: Alone Versus Combination

Abstract

The effects of vehicles and skin permeation enhancer on the skin permeation of dideoxynucleoside-type anti-HN drugs, Zalcitabine (DDC), Didanosine (DDI), and Zidovudine (AZT), alone and in combination, were compared using hairless rat and human cadaver skins. Each drug alone or a combination of three drugs was added to various compositions of ethanol/water or ethanol/tricaprylin cosolvent system to saturation, and in vitro skin permeation studies were conducted using Valia-Chien skin permeation cells. In both ethanol/water and ethanol/tricaprylin systems, the hairless rat skin permeation rates achieved by each drug alone and three drugs in combination were not significantly different. Addition of oleic acid [1.0% (v/v) for each drug alone and 5.0% (v/v) for drug combination] in ethanol/tricaprylin (50:50) could not significantly enhance the skin permeation of these drugs. In hairless rat skin permeation of each drug alone, the permeation rates of all three drugs were dramatically enhanced with the addition of oleic acid in ethanol/water (60:40) cosolvent system and reached plateau level with oleic acid as low as 0.3% (v/v). However, in the case of drug combination, the enhancement of skin permeation rates of these drugs with the addition of oleic acid in ethanol/water (80:20) cosolvent system was not as high as that observed for each drug alone, and plateau level was not observed even at 5.0% (v/v) of oleic acid. Human cadaver skin permeation rates of each drug alone saturated in ethanol/ water (60:40) cosolvent system containing 1.0% (v/v) of oleic acid were 3-4 times lower than those of hairless rat skin. However, in skin permeation of three drugs in combination, saturated in ethanol/water (80:20) cosolvent system containing 5.0% (v/v) of oleic acid, human cadaver skin permeation rates of DDC and DDI were slightly lower than those of hairless rat skin, and there was no significant difference between the two skins for AZT. These results show that mutual skin permeation-enhancing effects of oleic acid and an ethanol/water cosolvent system Made the transdermal delivery of anti-HIV drugs, alone and in combination, feasible.     

In vitro and in vivo evaluation of cubosomal in situ nasal gel containing resveratrol for brain targeting

The aim of this study was to enhance the delivery of resveratrol to the brain through the transnasal route by cubosomes. Cubosomes were prepared using glycerol monooleate and Lutrol F127 by probe sonication method. A 3² full factorial design was used for optimization of cubosomes and batch containing 4% w/v glycerol monooleate and 1.5% w/v of Lutrol F 127 was optimized. The selected cubosomal batch was cubical in shape, having mean particle size 161.5?±?0.12?nm. Entrapment efficiency was found to be 83.08% with zeta potential of –20.9?mV. In vitro release of cubosomal batch showed controlled release of drug profile (67%) up to 24?h. The optimized cubosomal dispersion was dispersed into gelling polymer (poloxamer 407) to form in situ gel for nasal use. The optimal cubosomal gel (containing 12% w/v poloxamer 407) had been subjected to ex-vivo permeation and in vivo biodistribution studies. It showed significantly higher transnasal permeation and better distribution to brain, when compared to the drug solution (i.n.) and drug solution (oral). Finally the cubosomal gel could be considered as a promising carrier for brain targeting of Resveratrol (Res) through transnasal route.     

Magnetophoresis in combination with chemical enhancers for transdermal drug delivery

Purpose: The objective of the present work was to investigate the effect of combination of a novel physical permeation enhancement technique, magnetophoresis with chemical permeation enhancers on the transdermal delivery of drugs.

Methods: The in vitro drug transport studies were carried out across the freshly excised abdominal skin of Sprague-Dawley rats using transdermal patch systems (magnetophoretic and non-magnetophoretic) of lidocaine hydrochloride (LH). LH gel prepared using hydroxypropyl methylcellulose (HPMC) was spread over the magnets as a thin layer. To investigate the effect of chemical permeation enhancers, menthol, dimethyl sulfoxide, sodium lauryl sulfate and urea (5% w/v) were incorporated in the gels prior to loading on the patch system.

Results: The flux of lidocaine from magnetophoretic patch was ~3-fold higher (3.07?±?0.43 µg/cm²/h) than that of the control (non-magnetophoretic patch) (0.94?±?0.13 µg/cm²/h). Incorporation of chemical permeation enhancers in the gel enhanced the magnetophoretic delivery flux by ~4 to 7-fold.

Conclusions: The enhancement factor due to combination of chemical permeation enhancer was additive and not synergistic. Mechanistic studies indicated that magnetophoresis mediated drug delivery enhancement was via appendageal pathway.     

Novel mucoadhesive oral patch containing diazepam

The oral patch of diazepam (DZ) was developed to achieve a rapid absorption of DZ for the emergency treatment of epileptic seizure or anxiety disorder. The patch was composed of the outer mucoadhesive Carbopol 934 region, central drug region, and Tegaderm backing film. DZ (3 mg) was dissolved in propylene glycol (PG) alone or PG containing oleic acid (OA) at 5.6% (w/w), and used as the drug region. The patches with and without OA were attached to the mucosa of cheek in rats. The patch with OA exhibited the plasma level of more than 200 ng/mL at 10 min after administration, then the plasma concentration decreased gradually. The patch without OA displayed a plasma level of less than 30 ng/mL during 40 min after administration. To the contrary, in the in vitro drug permeation using a cellulose membrane, the patch without OA showed a three times faster permeation rate than the patch with OA, suggesting that the direct action of OA to mucosa might be associated with absorption enhancement. It was demonstrated that the patch with OA showed a good adhesion to oral mucosa and worked efficiently for rapid absorption of DZ.     

Novel Mucoadhesive Oral Patch Containing Diazepam

The oral patch of diazepam (DZ) was developed to achieve a rapid absorption of DZ for the emergency treatment of epileptic seizure or anxiety disorder. The patch was composed of the outer mucoadhesive Carbopol 934 region, central drug region, and Tegaderm backing film. DZ (3 mg) was dissolved in propylene glycol (PG) alone or PG containing oleic acid (OA) at 5.6% (w/w), and used as the drug region. The patches with and without OA were attached to the mucosa of cheek in rats. The patch with OA exhibited the plasma level of more than 200 ng/mL at 10 min after administration, then the plasma concentration decreased gradually. The patch without OA displayed a plasma level of less than 30 ng/mL during 40 min after administration. To the contrary, in the in vitro drug permeation using a cellulose membrane, the patch without OA showed a three times faster permeation rate than the patch with OA, suggesting that the direct action of OA to mucosa might be associated with absorption enhancement. It was demonstrated that the patch with OA showed a good adhesion to oral mucosa and worked efficiently for rapid absorption of DZ.     

Thermoreversible nanoethosomal gel for the intranasal delivery of Eletriptan hydrobromide

The objective of the current study was to formulate and characterize thermoreversible gel of Eletriptan Hydrobromide for brain targeting via the intranasal route. Ethosomes were prepared by 3² factorial design with two independent variables (concentration of soya lecithin and ethanol) and two response variables [percent entrapment efficiency and vesicle size (nm)] using ethanol injection method. Formulated ethosomes were evaluated for preliminary microscopic examination followed by percent drug entrapment efficiency, vesicle size analysis, zeta potential, polydispersibility index and Transmission electron microscopy (TEM). TEM confirms spherical morphology of ethosomes, whereas Malvern zeta sizer confirms that the vesicle size was in the range of 191 ± 6.55–381.3 ± 61.0 nm. Ethosomes were incorporated in gel using poloxamer 407 and carbopol 934 as thermoreversible and mucoadhesive polymers, respectively. Ethosomal gels were evaluated for their pH, viscosity, mucoadhesive strength, in vitro drug release and ex vivo drug permeation through the sheep nasal mucosa. Mucoadhesive strength and pH was found to be 4400 ± 45 to 5500 ± 78.10 dynes/cm² and 6.0 ± 0.3 to 6.2 ± 0.1, respectively. In-vitro drug release from the optimized ethosomal gel formulation (G4) was found to be almost 100 % and ex vivo permeation of 4980 µg/ml with a permeability coefficient of 11.94 ± 0.04 × 10^?5 cm/s after 24 h. Histopathological study of the nasal mucosa confirmed non-toxic nature of ethosomal gels. Formulated EH loaded ethosomal thermoreversible gel could serve as the better alternative for the brain targeting via the intranasal route which in turn could subsequently improve its bioavailability.     

Preparation and evaluation of chitosan–itraconazole co-precipitated nanosuspension for ocular delivery

The purpose of the present study was to prepare itraconazole-loaded chitosan nanosuspension and evaluate it for ocular delivery. Itraconazole-loaded chitosan nanosuspension was prepared by controlled co-precipitation of chitosan and itraconazole from aqueous acetate solution using a combination of pH change and non-solvent addition. The co-precipitated suspension was evaluated for particle size, zeta-potential, entrapment efficiency and solubility study. It was observed that co-precipitation of itraconazole and chitosan from chitosan–lysine system in the presence of Poloxamer-188 as stabiliser provided nanosuspension of the smallest particle size with a 12-fold increase in aqueous saturation solubility of itraconazole and the fastest in vitro release. Transmission electron micrographs of the nanosuspension showed ovoid-shaped particles. A comparative evaluation of the itraconazole (1%, w/v) nanosuspension with commercial itraconazole suspension (1%, w/v) revealed a significantly higher percentage cumulative permeation of itraconazole across the isolated goat cornea from the nanosuspension dosage form as compared to the commercial suspension (P < 0.01).     

Influence of cross-linking agent type and chitosan content on the performance of pectinate-chitosan beads aimed for colon-specific drug delivery

Pectinate-chitosan-beads aimed for colon theophylline delivery have been developed. The effect of zinc or calcium ions as cross-linking agent, and of chitosan concentration on the properties and colon-targeting performance of beads was investigated. Beads were characterized for morphology, entrapment efficiency and mucoadhesion properties. Zn-pectinate-chitosan beads formed a stronger gel network than the Ca-containing ones, enabling a greater entrapment efficiency, which further increased with chitosan content, probably due to polyelectrolyte complexes formation. Transport studies across Caco-2 cells evidenced a significant (p > 0.05) drug permeation increase from all beads with respect to drug alone, attributable to the enhancer and/or mucoadhesion properties of the polymers, and Ca-pectinate-chitosan beads were more effective than the Zn-containing ones. Beads formulated as enteric-coated tablets demonstrated good colon-targeting properties, and no differences were observed in drug-release profiles from Zn- or Ca-pectinate-chitosan beads. Therefore, Ca-pectinate-chitosan beads emerged as the choice formulation, joining colon-targeting specificity with better permeation enhancer power.     

Design,characterization and ex vivo evaluation of chitosan film integrating of insulin nanoparticles composed of thiolated chitosan derivative for buccal delivery of insulin

The purpose of this study is to optimize and characterize of chitosan buccal film for delivery of insulin nanoparticles that were prepared from thiolated dimethyl ethyl chitosan (DMEC-Cys). Insulin nanoparticles composed of chitosan and dimethyl ethyl chitosan (DMEC) were also prepared as control groups. The release of insulin from nanoparticles was studied in vitro in phosphate buffer solution (PBS) pH 7.4. Optimization of chitosan buccal films has been carried out by central composite design (CCD) response surface methodology. Independent variables were different amounts of chitosan and glycerol as mucoadhesive polymer and plasticizer, respectively. Tensile strength and bioadhesion force were considered as dependent variables. Ex vivo study was performed on excised rabbit buccal mucosa. Optimized insulin nanoparticles were obtained with acceptable physicochemical properties. In vitro release profile of insulin nanoparticles revealed that the highest solubility of nanoparticles in aqueous media is related to DMEC-Cys nanoparticles. CCD showed that optimized buccal film containing 4% chitosan and 10% glycerol has 5.81?kg/mm² tensile strength and 2.47?N bioadhesion forces. Results of ex vivo study demonstrated that permeation of insulin nanoparticles through rabbit buccal mucosa is 17.1, 67.89 and 97.18% for chitosan, DMEC and DMEC-Cys nanoparticles, respectively. Thus, this study suggests that DMEC-Cys can act as a potential enhancer for buccal delivery of insulin.     

Transdermal delivery of car vedilol in rats: probing the percutaneous permeation enhancement mechanism of soybean extract–chitosan mixture

Background: This study was designed for investigating the effect of soybean (SS) extract and chitosan (CTN) in facilitating the permeation of carvedilol (CDL) across rat epidermis. Method: Transdermal flux of carvedilol through heat-separated rat epidermis was investigated in vitro using vertical Keshary–Chien diffusion cells. Biophysical and microscopic manifestations of epidermis treated with SS-extract, CTN, and SS extract–CTN mixture were investigated by using DSC, TEWL, SEM, and TEM. Biochemical estimations of cholesterol, sphingosine, and triglycerides were carried out for treated excised as well as viable rat epidermis. The antihypertensive activity of the patches in comparison to that after oral administration of carvedilol was studied in deoxycorticosterone acetate-induced hypertensive rats. Results: The solubility of CDL was found to be maximum in the presence of 1% (w/v) SS extract. The K_IPM/PB of CDL decreased with increase in concentration of SS extract. The in vitro permeation of CDL across rat epidermis increased and was maximum with combination of SS extract and chitosan (CTN). Biochemical and microscopic studies revealed the initiation of reversal of barrier integrity after 12 hours. Furthermore, the application of patches containing SS extract–CTN mixture resulted in sustained release of carvedilol, which was able to control the hypertension in deoxycorticosterone acetate (DOCA) induced hypertensive rats through 24 hours. CTN was found to potentiate the permeation enhancing activity of SS extract. Conclusion: The developed transdermal patches of CDL containing SS extract–CTN mixture exhibited better performance as compared to oral administration in controlling hypertension in rats.     

Design,characterization, and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting

Context: Parkinson disease (PD) is a common, progressive neurodegenerative disorder, characterized by marked depletion of striatal dopamine and degeneration of dopaminergic neurons in the substantia nigra.

Objective: The purpose of the present study was to investigate the possibility of targeting an anti-Parkinson’s drug ropinirole (RH) to the brain using polymeric nanoparticles.

Materials and methods: Ropinirole hydrochloride (RH)-loaded chitosan nanoparticles (CSNPs) were prepared by an ionic gelation method. The RH-CSNPs were characterized for particle size, polydispersity index (PDI), zeta potential, loading capacity, entrapment efficiency in vitro release study, and in vivo distribution after intranasal administration.

Results and discussion: The RH-CSNPs showed sustained release profiles for up to 18?h. The RH concentrations (% Radioactivity/g) in the brain following intranasal administration (i.n.) of RH-CSNPs were found to be significantly higher at all the time points compared with RH solution. The concentration of RH was highest in the liver (7.210?±?0.52), followed by kidneys (6.862?±?0.62), intestine (4.862?±?0.45), and lungs (4.640?±?0.92) in rats following i.n. administration of RH-CSNPs. Gamma scintigraphy imaging in rats was performed to ascertain the localization of drug in the brain following intranasal administration of formulations. The brain/blood ratios obtained (0.251?±?0.09 and 0.386?±?0.57 of RH (i.n.) and RH-CSNPs (i.n.), respectively) at 0.5?h are indicative of direct nose to brain transport, bypassing the blood–brain barrier (BBB).

Conclusion: The novel formulation showed the superiority of nose to brain delivery of RH using mucoadhesive nanoparticles compared with other delivery routes reported earlier.     

Influence of cross-linking agent type and chitosan content on the performance of pectinate-chitosan beads aimed for colon-specific drug delivery

Pectinate-chitosan-beads aimed for colon theophylline delivery have been developed. The effect of zinc or calcium ions as cross-linking agent, and of chitosan concentration on the properties and colon-targeting performance of beads was investigated. Beads were characterized for morphology, entrapment efficiency and mucoadhesion properties. Zn-pectinate-chitosan beads formed a stronger gel network than the Ca-containing ones, enabling a greater entrapment efficiency, which further increased with chitosan content, probably due to polyelectrolyte complexes formation. Transport studies across Caco-2 cells evidenced a significant (p?>?0.05) drug permeation increase from all beads with respect to drug alone, attributable to the enhancer and/or mucoadhesion properties of the polymers, and Ca-pectinate-chitosan beads were more effective than the Zn-containing ones. Beads formulated as enteric-coated tablets demonstrated good colon-targeting properties, and no differences were observed in drug-release profiles from Zn- or Ca-pectinate-chitosan beads. Therefore, Ca-pectinate-chitosan beads emerged as the choice formulation, joining colon-targeting specificity with better permeation enhancer power.     

Formulation of sage essential oil (Salvia officinalis,L.) monoterpenes into chitosan hydrogels and permeation study with GC-MS analysis

This study deals with the formulation of natural drugs into hydrogels. For the first time, compounds from the sage essential oil were formulated into chitosan hydrogels. A sample preparation procedure for hydrophobic volatile analytes present in a hydrophilic water matrix along with an analytical method based on the gas chromatography coupled with the mass spectrometry (GC-MS) was developed and applied for the evaluation of the identity and quantity of essential oil components in the hydrogels and saline samples. The experimental results revealed that the chitosan hydrogels are suitable for the formulation of sage essential oil. The monoterpene release can be effectively controlled by both chitosan and caffeine concentration in the hydrogels. Permeation experiment, based on a hydrogel with the optimized composition [3.5% (w/w) sage essential oil, 2.0% (w/w) caffeine, 2.5% (w/w) chitosan and 0.1% (w/w) Tween-80] in donor compartment, saline solution in acceptor compartment, and semi-permeable cellophane membrane, demonstrated the useful permeation selectivity. Here, (according to lipophilicity) an enhanced permeation of the bicyclic monoterpenes with antiflogistic and antiseptic properties (eucalyptol, camphor and borneol) and, at the same time, suppressed permeation of toxic thujone (not exceeding its permitted applicable concentration) was observed. These properties highlight the pharmaceutical importance of the developed chitosan hydrogel formulating sage essential oil in the dermal applications.     

Preparation and characterization of malonic acid cross-linked chitosan and collagen 3D scaffolds: an approach on non-covalent interactions

The present study emphasizes the influence of non-covalent interactions on the mechanical and thermal properties of the scaffolds of chitosan/collagen origin. Malonic acid (MA), a bifuncitonal diacid was chosen to offer non-covalent cross-linking. Three dimensional scaffolds was prepared using chitosan at 1.0% (w/v) and MA at 0.2% (w/v), similarly collagen 0.5% (w/v) and MA 0.2% (w/v) and characterized. Results on FT-IR, TGA, DSC, SEM and mechanical properties (tensile strength, stiffness, Young’s modulus, etc.) assessment demonstrated the existence of non-covalent interaction between MA and chitosan/collagen, which offered flexibility and high strength to the scaffolds suitable for tissue engineering research. Studies using NIH 3T3 fibroblast cells suggested biocompatibility nature of the scaffolds. Docking simulation study further supports the intermolecular hydrogen bonding interactions between MA and chitosan/collagen.