Modified karaya gum colloidal particles for the management of systemic hypertension.

This study undertakes the development of colloidal carriers for the purpose of oral delivery of bosentan and subsequent management of systemic hypertension. Karaya gum, a natural polymer was carboxymethylated to improve its hydrophilic character and then the carboxymethyl gum was hydrophobically modified by forming propyl ethers. The modified polymer acquired amphiphilic property and self-aggregated in water to form amphiphilic colloidal particles (ACPs) at critical concentration of 3.35 mg/L with spherical shape (<200 nm) and smooth surface morphology. The colloidal particles could entrap >90% drug in the lipophilic domain. The ionic crosslinking of the hydrophilic shell of ACPs imparted greater stability to the colloidal system. The crosslinking extended the duration of drug release under simulated gastrointestinal fluids. The crystalline drug physically turned into amorphous state after hosting into the lipophilic cores of ACPs. The entrapment resulted in significant improvement of drug dissolution rate. The polymer relaxation contributed to the diffusion process of drug from ACPs. Pre-clinical testing via oral route demonstrated that the crosslinked colloidal particles could effectively control the systemic hypertension over a period of 12 h. Hence, bosentan-loaded self-assembled colloidal particles may advance the management of systemic hypertension.

Novel propyl karaya gum nanogels for bosentan: In vitro and in vivo drug delivery performance.

The amphiphilic propyl Karaya gum (KG) with a degree of propyl group substitution of 3.24 was synthesized to design self-assembled nanogels as carriers for bosentan monohydrate, a poorly soluble antihypertensive drug. The drug was physically hosted into the hydrophobic core of the micellar nanogels by solvent evaporation method. TEM images revealed spherical shape and core-shell morphology of the nanogels. Depending upon polymer: drug weight ratio, the drug entrapment efficiency of >85% was attained. The carriers had hydrodynamic diameter in the range of 230-305 nm with narrow size distribution. The zeta potential of -23.0 to -24.9 mV and low critical association concentration (CAC) of 8.32 mg/l provided evidence that the colloidal nanogel system was physically stable. Thermodynamics of the propyl KG system in water favored spontaneous self-assembly of propyl KG. FTIR, thermal and x-ray analyses suggested that the drug was compatible in the hydrophobic confines of the nanogels. The micellar nanogels liberated their contents in simulated gastrointestinal condition in a pH-dependent manner over a period of 10 h. Peppas-Sahlin modeling of in vitro drug release data suggested that the polymer relaxation/swelling mechanism dominated the drug release process. Pre-clinical testing of the mucoadhesive nanogel formulations exhibited that the system could monitor the anti-hypertensive activity for a prolonged period. Overall, this propyl KG micellar nanogel system had a great potential and splendid outlook to serve as novel oral controlled release carriers for poorly soluble drugs with outstanding pharmacodynamics.

Smart karaya-locust bean gum hydrogel particles for the treatment of hypertension: Optimization by factorial design and pre-clinical evaluation.

This investigation was undertaken to unveil the controlled drug delivery and preclinical anti-hypertensive potential of a novel interpenetrating biopolymer-based network of karaya gum and carboxymethyl locust bean gum (CLBG). The Williamson synthesis of CLBG was confirmed after analyzing FTIR spectra, degree of O-carboxymethyl group substitution and viscosity. The hydrogel particles (HPs) were developed using aluminium chloride solution as cross-linker. A full 32 factorial design approach was adopted for the optimization of two responses: drug entrapment efficiency and drug release (%) in simulated gastrointestinal conditions at 10 h. FE-SEM images and EDX spectra supported the formation of spherical HPs and successful entrapment of the drug in the HPs. Depending upon formulation variables, the drug entrapment efficiency of the HPs lied in the range of 84-98%. The HP matrix was chemically compatible for carvedilol phosphate as was suggested by infrared, thermal and x-ray analyses. The swelling kinetics of HPs corroborated well with the pH-dependent in vitro drug discharge characteristics. The drug release from HPs was found to follow anomalous transport mechanism with varying contribution of simple diffusion and polymer relaxation as was elucidated by Peppas-Sahlin model equation. Preclinical data suggested that the optimized HPs had an excellent blood pressure lowering activity in male Swiss albino mice up to 10 h.

Chitosan - Locust bean gum interpenetrating polymeric network nanocomposites for delivery of aceclofenac.

In this study, aceclofenac-loaded IPN nanocomposites were developed based on natural polysaccharides namely chitosan (CS) and locust bean gum (LBG) using glutaraldehyde as cross-linker. Infrared spectroscopy analysis confirmed the formation of composite materials and ensured the chemical compatibility between drug and polymers. The effect of component polymers on the drug entrapment efficiency (DEE) and particle size of the composites was examined. Increasing LBG content actually decreased the DEE from 72% to 40% and produced larger particles of 372-485nm dimensions. However, an opposite trend was noted as the concentration of CS was increased. Out of these composites, the maximum drug entrapment efficiency of 78.92% and smallest composites of 318nm-size was obtained at LBG: CS mass ratio of 1:5. However, CS: LBG (1:5) provided the slowest drug release profiles in phosphate buffer solution (pH 6.8) up to 8h. The drug release data corroborated well with the swelling properties of the nanocomposites. The composite systems efficiently suppressed the burst release of drug in acidic medium (pH 1.2). The drug delivery from the nanocomposites occurred via anomalous transport mechanism in vitro. Overall, this novel chitosan- and LBG-based nanocomposites system could minimize the gastrointestinal side effects of the drug by providing medication in a slow sustained fashion.

Gelatin-carboxymethyl tamarind gum biocomposites: In vitro characterization & anti-inflammatory pharmacodynamics.

In this study, gelatin and carboxymethyl tamarind gum (CTG) were chemically cross-linked to control the delivery of aceclofenac from their interpenetrating network (IPNs). Infrared spectra, thermal and X-ray data supported that drug and polymer was compatible in the composite hydrogels. Irregularly shaped IPN microstructures were seen under field emission scanning electron microscope (FE-SEM). IPN system was capable of entrapping about 96% of the drug fed. CTG in IPN structures suppressed the drug release rate in HCl solution (pH1.2); however extended the same in phosphate buffer solution (pH6.8). The drug release was controlled by polymer chain relaxation/swelling and simple diffusion in vitro. The anti-inflammatory activity of drug-loaded biocomposites lasted over 7h in albino rats, thus suggesting their potential as an anti-inflammatory therapeutics.

Interpenetrating hydrogels of O-carboxymethyl Tamarind gum and alginate for monitoring delivery of acyclovir.

In this work, an interpenetrating hydrogel network was constructed using varying combination of O-carboxymethyl Tamarind gum (CTG) and alginate by Ca+2 ion induced gelation method. The hydrogels were characterized by FTIR spectroscopy, Field emission scanning electron microscopy (FESEM), energy dispersive X-ray (EDX) and differential scanning calorimetry (DSC) analyses. The hydrogels were spherical in shape with rough surface textures. Depending on the alginate: CTG mass ratio, the hydrogel particles entrapped a maximum of ∼70% acyclovir. The drug release from interpenetrating hydrogels was 18-23% in HCl solution (pH1.2) in 2h. The drug release became faster in phosphate buffer solution (pH6.8) as the proportion of CTG was increased from 25% to 50%. However, the drug release was still slower than that observed for hydrogel particles of sodium alginate alone. Overall, the drug release tendency of the particles was higher in phosphate buffer solution than that in HCl solution. The non-Fickian drug release behavior was assumed after fitting the drug release data into Korsmeyer-Peppas model. The drug release was found to control by diffusion and swelling kinetics of the hydrogels. Thus, CTG gum could effectively retard drug release when used in combination with sodium alginate at an optimized mass ratio.

Alginate Based Nanocarriers for Drug Delivery Applications.

BACKGROUND: Now a day's natural polymer based nanoparticulate system have been widely studied as particulate vehicles in the bio-medical and pharmaceutical area. Alginate, a natural biopolymer show good biodegradability, biocompatibility and non toxic, has received attention to utilise as a carrier for preparation of polymeric nanoparticles. Chemically and physically alginate can modified easily and obtained various structure having various properties, and versatile applications. Various properties and structure such as biodegradability, gelling property, mechanical strength and cell affinity can be obtained through combination of alginate with other biopolymers, immobilization of specific molecules such as sugar molecules and peptide through chemical or physical cross-linking. CONCLUSION: In this article, we report different method of preparation of alginate nanoparticles, and also focus on recent advances of nanoparticles made of alginate and its modified form in the field of drug delivery applications.

Biosurfactant produced from Actinomycetes nocardiopsis A17: Characterization and its biological evaluation.

This investigation aims to isolate an Actinomycetes strain producing a biosurfactant from the unexplored region of industrial and coal mine areas. Actinomycetes are selected for this study as their novel chemistry was not exhausted and they have tremendous potential to produce bioactive secondary metabolites. The biosurfactant was characterized and further needed to be utilized for pharmaceutical dosage form. Isolation, purification, screening, and characterization of the Actinomycetes A17 were done followed by its fermentation in optimized conditions. The cell-free supernatant was used for the extraction of the biosurfactant and precipitated by cold acetone. The dried precipitate was purified by TLC and the emulsification index, surface tension and CMC were determined. The isolated strain with preferred results was identified as Actinomycetes nocardiopsis A17 with high foam-forming properties. It gives lipase, amylase, gelatinase, and protease activity. The emulsification index was found to be 93±0.8 with surface tension 66.67 dyne/cm at the lowest concentration and cmc 0.6 µg/ml. These biosurfactants were characterized by Fourier transform infra red (FT-IR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS). Therefore, it can be concluded that the biosurfactant produced by Actinomycetes nocardiopsis sp. strain A17 was found to have satisfactory results with high surface activity and emulsion-forming ability.

Development and characterization of alginate coated low molecular weight chitosan nanoparticles as new carriers for oral vaccine delivery in mice.

In the present study, nanoparticles of low MW chitosan (CS) were formulated in which measles antigen was entrapped and subsequently coated with sodium alginate. The size and surface properties of the nanoparticle can be tuned with different MW of CS. In vitro release studies showed initial burst release followed by extended release, best fitted in the Makoid-Banakar model (R(2)>0.98). SDS-PAGE assay revealed that alginate coating could effectively protect antigen in acidic condition for at least 2h. Cell viability was assessed using MTT assay into HT 29 cell line. Formulations were orally administered to mice and immunological responses were evaluated using ELISA method. Obtained results showed that measles antigen-loaded CS nanoparticles induced strong immune response and significant correlation was observed between the immune response with CS MW. Protecting ability of antigen in gastric environment, sustained release kinetics, systemic and mucosal immune responses and low cytotoxicity observed for the alginate coated nanoparticles demonstrated that LMW CS could be promising platform for oral vaccine delivery.

Novel alginate hydrogel core-shell systems for combination delivery of ranitidine HCl and aceclofenac.

A novel hydrogel system was successfully developed based on core-shell approach for the delivery of ranitidine HCl and aceclofenac. Aceclofenac-loaded alginate microspheres coated with eudragit L-100 was used as core material and that of freeze-thaw cross-linked chitosan-PVA gels containing ranitidine HCl served as the shell-forming material. The alginate microspheres coated with eudragit L-100 showed drug encapsulation efficiency of 56.06±1.12 to 68.03±2.16% and had average particle sizes of 551.29±25.92 to 677.18±27.05 µm. The viscosity of chitosan-PVA gels ranged between 505.74±1.04 and 582.41±2.09 cps. The formulations were characterized by FTIR, SEM and polarized microscopy analyses. The release of ranitidine HCl was comparatively higher in acidic medium (pH 1.2) than in alkaline medium (pH 7.4). The release of aceclofenac became slower in alkaline medium (pH 7.4) and continued up to 3.5 h. Super case-II transport mechanism was assumed for the release of ranitidine HCl in both media; whereas non-Fickian (anomalous) diffusion mechanism predominated in the release of aceclofenc. Thus, hydrogel-based core-shell formulations were found suitable for simultaneous delivery of aceclofenac and ranitidine HCl which could minimize the chances of excessive gastric acid secretion through suitable ranitidine HCl release in gastric region.

Metal ion-induced alginate-locust bean gum IPN microspheres for sustained oral delivery of aceclofenac.

The alginate microspheres represent a useful tool for sustained oral delivery of drugs but exhibit several problems associated with the stability and rapid release of drugs at higher pH values. To overcome these drawbacks, alginate-locust bean gum (LBG) interpenetrating microspheres were prepared by calcium ion (Ca(+2)) induced ionotropic gelation technique for prolonged release of aceclofenac. The drug entrapment efficiency of these microspheres was found to be 59-93%. The microspheres lied in the size range of 406-684µm. Scanning electron microscopy revealed spherical shape of the microspheres. No drug-polymer interaction was evident after infrared spectroscopy analysis. The microspheres provided sustained release of aceclofenac in phosphate buffer solution (pH 6.8) over a period of 8h. The drug release data were fitted into the Korsmeyer-Peppas model and the drug release was found to follow anomalous (non-Fickian) diffusion mechanism. Pharmacodynamic study of the microspheres showed a prolonged anti-inflammatory activity in carrageenan-induced rat paw model following oral administration.

Gellan gum microspheres containing a novel α-amylase from marine Nocardiopsis sp. strain B2 for immobilization.

A Nocardiopsis sp. stain B2 with an ability to produce stable α-amylase was isolated from marine sediments. The characterization of microorganism was done by biochemical tests and 16S rDNA sequencing. The α-amylase was purified by gel filtration chromatography by using sephadex G-75. The molecular mass of the amylase was found to be 45 kDa by SDS-PAGE and gel filtration chromatography. The isolated α-amylase was immobilized by ionotropic gelation technique using gellan gum (GG). These microspheres were spherical with average particle size of 375.62±21.76 to 492.54±32.18 µm. The entrapment efficiency of these α-amylase loaded GG microspheres was found 74.76±1.32 to 87.64±1.52%. Characterization of α-amylase-gellan gum microspheres was confirmed using FTIR and SEM analysis. The in vitro amylase release kinetic have been studied by various mathematical models that follow the Korsmeyer-Peppas model (R2=0.9804-0.9831) with anomalous (non-Fickian) diffusion release mechanism.

In-vitro release of acyclovir loaded Eudragit RLPO(®) nanoparticles for sustained drug delivery.

In this present study the possibility to develop Eudragit RLPO(®) based nanoparticles of acyclovir was investigated in order to increase its efficacy because acyclovir has oral bioavailability of only 10-20% thus showing erratic absorption and bioavailability behaviour. The nanoparticles were prepared by nanoprecipitation technique. Pluronic F68 was used as stabilizer. The nanoparticles were characterized by particle size, entrapment efficiency, DSC, SEM, FTIR and in-vitro drug release. It was found that as drug:polymer (Acyclovir:Eudragit RLPO(®)) ratio increased from 1:1.5 to 1:2, particle size was increased significantly and drug entrapment also increased but thereafter, further increase in drug: polymer ratio showed reduced or insignificant change in the drug entrapment efficiency. DSC results showed that in the prepared nanoaprticles, the drug was present in the amorphous phase and may have been homogeneously dispersed in the polymer matrix. In vitro drug release study of formulations showed release in 24h in the range 71.62±1.72 to 93.25±1.02%. The release was found to follow Higuchi model with non-Fickian diffusion mechanism for all batches. These preliminary results indicate that acyclovir loaded Eudragit RLPO(®) nanoparticles could be effective in sustaining drug release for a prolonged period.

In vitro aceclofenac release from IPN matrix tablets composed of chitosan-tamarind seed polysaccharide.

This communication describes the formulation and in vitro evaluation of IPN matrix tablets of aceclofenac. IPN microparticles using chitosan and tamarind seed polysaccharide blend was prepared using glutaraldehyde as cross-linker. The drug entrapment efficiency and average particle size of these microparticles was found to be 91.97±1.30% and 498.12±38.67 µm, respectively. These IPN microparticles were characterized by scanning electron microscopy (SEM) and powder X-ray diffraction (P-XRD) study. These microparticles were compressed with tablet excipients through direct compression technique. These matrix tablets showed sustained aceclofenac release over 8 h. These matrix tablets might be helpful to minimize dosing frequency and reduction of various side effects during prolong period of treatment.

Carbopol gel containing chitosan-egg albumin nanoparticles for transdermal aceclofenac delivery.

In the present work, various aceclofenac-loaded chitosan-egg albumin nanoparticles were prepared through heat coagulation method. These aceclofenac-loaded nanoparticles were characterized by FE-SEM, FTIR, DSC and P-XRD analyses. The in vitro drug release from nanoparticles showed sustained drug release over 8h. Aceclofenac-loaded nanoparticles (prepared using 200mg chitosan, 500 mg egg albumin and 2% (w/v) NaTPP) showed highest drug entrapment (96.32±1.52%), 352.90 nm average particle diameter and -22.10 mV zeta potential, which was used for further preparation of Carbopol 940 gel for transdermal application. The prepared gel exhibited sustained ex vivo permeation of aceclofenac over 8h through excised mouse skin. The in vivo anti-inflammatory activity in carrageenean-induced rats demonstrated comparative higher inhibition of swelling of rat paw edema by the prepared gel compared with that of the marketed aceclofenac gel over 4 h.

Development of chitosan-based nanoparticles through inter-polymeric complexation for oral drug delivery.

The possibility of inter-polymeric complexation of cationic chitosan and anionic egg albumin stabilized with PEG 400 to develop novel nanoparticles for oral delivery of alprazolam by heat coagulation method at pH 5.4 and 80 °C. Nine formulations were prepared by changing the concentration of chitosan, PEG 400 and heating time. The alprazolam entrapment efficiency of these nanoparticles was in the range of 68.12±1.27 to 99.37±4.86%. These nanoparticles were characterized by FTIR, DSC, P-XRD and FE-SEM analysis. Average particle diameter, poly-dispersity index and zeta potential of these nanoparticles were found 259.60 nm, 0.501, and -9.00 mV, respectively. The in vitro drug release from these alprazolam-loaded nanoparticles showed sustained drug release over a period of 24h. In conclusion, these newly developed chitosan-egg albumin-PEG nanoparticles were found to be a promising vehicle for sustained release delivery of lipophilic drugs.

Aceclofenac-loaded unsaturated esterified alginate/gellan gum microspheres: in vitro and in vivo assessment.

Aceclofenac-loaded alginate/gellan gum microspheres for prolonged aceclofenac release were prepared through maleic anhydride-induced unsaturated esterification. The drug entrapment efficiency of these microspheres was found 39.30 ± 1.28% to 98.46 ± 0.40% and their average particle sizes were 270-490 µm. These microspheres were characterized by FTIR, DSC, P-XRD and SEM analysis. The in vitro dissolution indicated prolonged sustained release of aceclofenac over 6h, which also followed the Korsmeyer-Peppas model (R(2)=0.9571-0.9952). The microspheres prepared through 3% (w/v) maleic anhydride-induced esterification exhibited comparatively slower drug-release. Most of the microspheres were followed Fickian diffusion mechanism except the microspheres containing higher gellan gum content, which followed anomalous (non-Fickian) diffusion. The in vivo results showed sustained systemic absorption of aceclofenac in rabbits and excellent anti-inflammatory activity in carrageenan-induced rats after oral administration over prolonged period.

Aceclofenac-loaded chitosan-tamarind seed polysaccharide interpenetrating polymeric network microparticles.

The present work deals with the preparation, characterization and evaluation of glutaraldehyde cross-linked chitosan-tamarind seed polysaccharide (TSP) interpenetrating polymeric network (IPN) microparticles for prolonged aceclofenac release. The drug entrapment efficiency of these microparticles was found 85.84±1.75 to 91.97±1.30% and their average particle sizes were ranged from 490.55±23.24 to 621.60±53.57 µm. These chitosan-TSP IPN microparticles were characterized by FTIR, DSC, and SEM analyses. The in vitro drug release from these aceclofenac-loaded chitosan-TSP IPN microparticles showed sustained release of aceclofenac over 8h and followed the Korsmeyer-Peppas model (R(2)=0.9809-0.9828) with anomalous (non-Fickian) diffusion drug release mechanism. The in vivo studies exhibited sustained anti-inflammatory activity in carrageenan-induced rats over prolonged period after oral administration of these newly developed aceclofenac-loaded IPN microparticles.

Formulation, optimization and evaluation of transferosomal gel for transdermal insulin delivery.

The present study deals with the development of transferosomal gel containing insulin by reverse phase evaporation method for painless insulin delivery for use in the treatment of insulin dependent diabetes mellitus. The effect of independent process variables like ratio of lipids (soya lecithin:cholesterol), ratio of lipids and surfactants, and ratio of surfactants (Tween 80:sodium deoxycholate) on the in vitro permeation flux (µg/cm(2)/h) of formulated transferosomal gels containing insulin through porcine ear skin was optimized using 2(3) factorial design. The optimal permeation flux was achieved as 13.50 ± 0.22 µg/cm(2)/h with drug entrapment efficiency of 56.55 ± 0.37% and average vesicle diameter range, 625-815 nm. The in vitro insulin permeation through porcine ear skin from these transferosomal gel followed zero-order kinetics (R (2) = 0.9232-0.9989) over a period of 24 h with case-II transport mechanism. The in vitro skin permeation of insulin from optimized transferosomal gel by iontophoretic influence (with 0.5 mA/cm(2) current supply) also provided further enhancement of permeation flux to 17.60 ± 0.03 µg/cm(2)/h. The in vivo study of optimized transferosomal gel in alloxan-induced diabetic rat has demonstrated prolonged hypoglycemic effect in diabetic rats over 24 h after transdermal administration.

Development of hydroxyapatite-ciprofloxacin bone-implants using "Quality by design".

The present study deals with the development of hydroxyapatite (HAp)-ciprofloxacin bone-implants using the ¼Quality by design« approach. The effect of various synthesis parameters like drug amount added in the process, stirring speed and addition rate of orthophosphoric acid in the synthesis on drug concentration in the HAp-ciprofloxacin system synthesized by the precipitation technique using 23 factorial design was analyzed. Optimization methodology utillizing the first-order polynomial equation was used to search for optimal drug concentration in the HAp-ciprofloxacin implant system. The observed responses coincided well with the predicted values from the optimization technique. New implants were manufactured using various HAp-ciprofloxacin composites and 1.5 % (m/V) guar gum as a binder. Characterization of the delivery system was done by XRPD, FTIR spectroscopy and SEM. Even at highest drug concentration (76.6 ± 0.5 %, m/m), ciprofloxacin was present in noncrystalline state. The in vitro ciprofloxacin release from various bone-implants was sustained for several weeks and the drug release pattern correlated well with the Korsmeyer- Peppas model.