Therapeutic Effectiveness in the Treatment of Experimental Bacterial Keratitis with Ion-activated Mucoadhesive Hydrogel.

PURPOSE: To investigate the therapeutic effectiveness of ion-activated mucoadhesive hydrogel system in the treatment of experimental bacterial keratitis. MATERIALS AND METHODS: Mucoadhesive systems were prepared using gellan or sodium alginate alone and combined with sodium carboxymethylcellulose (NaCMC) to enhance the gel bioadhesion properties. The in vivo antimicrobial efficacy of selected mucoadhesive systems was studied in an experiment on bacterial keratitis in rabbit's eyes and compared with that of the marketed conventional eyedrops. RESULTS: Ocular tolerance was studied in the eye of albino rabbits and tested formulations were non-irritant with no sign of inflammation. Better improvement in experimental bacterial keratitis in rabbit eyes was observed in animals treated with mucoadhesive hydrogel formulation (GG5 and GS5) compared with marketed drug solution. CONCLUSION: The developed system is a viable alternative to conventional eyedrops of GTN due to its ability to enhance bioavailability through its longer precorneal residence time.

Carbon nanotubes: an emerging drug carrier for targeting cancer cells.

During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review.

Studies on biological macromolecules lipid-Gelucire based gastroretentive multiparticulate.

Studies on biological macromolecules lipid-Gelucire based sustained release gastroretentive multiparticulates of metformin hydrochloride (MH) were developed by dispersing MH in melted Gelucire 39/01 and 43/01 using the melt granulation technique while fast release solid dispersions gastroretentive multiparticulates of glibenclamide (GLB), poorly soluble drug were developed using Gelucire 50/13 and PEG 200, 400, 4000, 6000 as carrier at different ratios. Percent drug entrapment of MH was 99.6±0.35% and in vitro floating ability was 11.3±0.47h. Model dependent analysis shows that zero order kinetics was followed while drug release mechanism was anomalous diffusion controlled. Combination of ethylcellulose, methylcellulose and microcrystalline cellulose with Gelucire were explored for release of drug, floatability and consistency for optimized formulation. While GLB multiparticulates showed entrapment efficiency of 99.8±0.11%, in vitro buoyancy for 11±0.2h and improved solubility and dissolution rate. Zero order kinetics was promising for all formulations. Model independent analysis f2 value for GIV was 40 while for M II was 54. Characterization was done by SEM, FTIR and PXRD. RP-HPLC method was adopted for simultaneous pharmacokinetic analysis of the drugs in rat plasma. In IVIVC studies confirm increased bioavailability of drugs in combination form and followed level A correlation using the diabetic type II Wistar rat.

Positively charged microemulsions of dexamethasone: comparative effects of two cosurfactants on ocular drug delivery and bioavailability.

BACKGROUND: The objective of this investigation was to evaluate the potential of mucoadhesive chitosan-coated positively charged microemulsions (CH-MEs) of dexamethasone with respect to the change in nonionic cosurfactants. METHODS: CH-MEs were prepared with different concentrations of surfactant and cosurfactant using the water titration method and coated with low-molecular-weight chitosan. RESULTS: All formulations displayed an average globule size between 85 and 187 nm and a positive surface charge. The optimized CH-MEs showed greater penetration of dexamethasone in the anterior segment of the eye, resulting in twofold and fourfold higher dexamethasone concentration than uncoated ME and drug suspension, respectively. CONCLUSION: The developed CH-MEs shows increases in ocular penetration and bioavailability.

Mucoadhesive chitosan-coated cationic microemulsion of dexamethasone for ocular delivery: in vitro and in vivo evaluation.

PURPOSE: Dexamethasone (DXN) is an effective anti-inflammatory drug in the treatment of acute and chronic eye disease such as uveitis. However, its low aqueous solubility limits its clinical usefulness. The purpose of this study was to investigate the mucoadhesive chitosan-coated cationic microemulsions (CH-MEs) for ophthalmic delivery of DXN to treat uveitis. MATERIALS AND METHODS: The pseudo-ternary phase diagrams were developed and various MEs were prepared using isopropyl myristate as oil, Tween 80 as a surfactant, propylene glycol as a co-surfactant and distilled water. MEs were prepared and coated with chitosan by the dropwise addition of chitosan solution in the ME dispersion. Physicochemical parameters (globule size, zetapotential, drug content, viscosity, refractive index and pH), mucoadhesive properties and the in vitro release of MEs were studied. The in vivo efficacy of prepared formulations and the marketed drug solution were studied by administering them topically to endotoxin-induced uveitis rabbit model. RESULTS: All formulations displayed an average globule size less than 200 nm and a positive surface charge. The developed CH-MEs showed acceptable physico-chemical behavior, good mucoadhesive properties, good stability for three months and exhibited sustained drug release. In vivo studies in rabbit eye showed a marked improvement in the anti-inflammatory activity of mucoadhesive CH-ME-treated eye compared with a marketed suspension formulation in a uveitis-induced rabbit eye model. CONCLUSION: The developed CH-MEs are a viable alternative to conventional eye drops for its ability to enhance bioavailability through its longer precorneal residence time and its ability to sustain the release of the drug.

Effect of hydroxypropyl-ß-cyclodextrin on the ocular bioavailability of dexamethasone from a pH-induced mucoadhesive hydrogel.

PURPOSE: Dexamethasone (DXN) is an effective anti-inflammatory drug in the treatment of acute and chronic eye disease such as uveitis. It is relatively lipophilic and permeates biological membranes quite easily. However, its low aqueous solubility limits its clinical usefulness. To circumvent this problem Hydroxypropyl-ß-cyclodextrin (HP-ß-CD) was used as solubilizer and penetration enhancer for DXN. The purpose of this study was to develop HP-ß-CD based pH-induced mucoadhesive hydrogel for ophthalmic delivery of DXN to treat uveitis. MATERIALS AND METHODS: The formation of inclusion complex of DXN with HP-ß-CD was characterized in solution and solid states by phase solubility, X-ray diffractometry and IR spectrum analyses. To improve ocular retention and sustained action Carbopol 980 NF and sodium carboxymethylcellulose (NaCMC) were added to the formulations as phase transition and mucoadhesive agents, respectively. RESULTS: The HP-ß-CD-based hydrogel system enhanced the solubility of DXN and the apparent stability constant (k') of the DXN-HP-ß-CD inclusion complex was found to be 258.62 M(-1). The optimum concentrations of Carbopol 980NF and NaCMC for the mucoadhesive hydrogel were 0.2% (w/v) and 0.4% (w/v), respectively. This mucoadhesive hydrogel could flow freely under non-physiological condition and showed the character of pseudoplastic fluid under both physiological and non-physiological conditions. In vitro release of DXN from the HP-ß-CD complex in simulated tear fluid (STF, pH- 7.4), was influenced significantly by the properties and concentration of Carbopol and NaCMC. In vivo studies in rabbit eye showed a marked improvement in anti-inflammatory activity of mucoadhesive hydrogel-treated eye compared with a marketed solution formulation in a uveitis-induced rabbit eye model. CONCLUSION: The developed HP-ß-CD-based mucoadhesive system is a viable alternative to conventional eye drops of DXN due to its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain the release of the drug.

In-vitro and in-vivo study of indomethacin loaded gelatin nanoparticles.

The present research work deals with fabrication of indomethacin loaded gelatin nanoparticles prepared by double desolvation method for controlled drug delivery. Submicron polymeric particles with size < 800 nm were produced possessing narrow polydispersity index (< 0.5). Entrapment efficiency varied from 27-38% depending upon particle size. No drug polymer interaction was observed by FTIR. DSC study confirmed amorphous nature of nanoparticles. The in-vitro drug release profile showed initial burst release (> 20% in 1 hr) followed by controlled release (> 75% in 12 hr). Among the kinetic models employed, the Higuchi model showed a better fit (R2 > 0.9) with n < 0.43 (Peppas model) indicating a Fickian type of release pattern. The batch 2GA was optimum in terms of size, entrapment efficiency and drug release. Anti-inflammatory activity of the drug loaded nanoparticles (IGNP) and pure drug solution (IDM) was studied by rat paw model and IGNP significantly (P < or = 0.001) decreased the paw volume as compared to IDM. Pharmacokinetic study showed significant enhancement (P < 0.001) of various pharmacokinetic parameters. The observed t(max) value was 3 h for IGNP compared to 1 h for IDM. Cmax of IGNP had higher value (110.81 +/- 8.53 microg/mL) compared to that of IDM (51.66 +/- 7.5 microg/mL). AUC0-12 was 1009.78 +/- 80.24 and 194.33 +/- 46.76/microg x h/mL in IGNP and IDM respectively (relative bioavailability 500%). Further, a good in vitro-in vivo correlation established the formulation for future trials.

Lomustine loaded chitosan nanoparticles: characterization and in-vitro cytotoxicity on human lung cancer cell line L132.

The aim of this work was to prepare chitosan nanoparticles loaded with antineoplastic drug Lomustine (LCNPs), by ionic-gelation method with homogenization. The nanoparticles were characterized for particle size, polydispersity index (PDI), surface morphology, encapsulation efficiency, in-vitro drug release and cytotoxicity on human lung cancer cell line L132 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The particle size, zeta potential and encapsulation efficiency of prepared nanoparticles ranged from 75 ± 1.1 to 637 ± 1.6 nm (PDI from 0.05 ± 0.001 to 0.18 ± 0.007), 37.2 ± 0.21 to 53.8 ± 0.18 mV and 66.74 ± 1.4 to 98.0 ± 1.8% respectively. The particles were spherical in shape with smooth surface in scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images. Mechanical shearing by homogenization treatment significantly changed the nanoparticle size. The drug release rate was biphasic and diffusion controlled over the 8 h. LCNPs greatly inhibited the growth of the L132 cancer cell line used in this study in comparison to the native Lomustine (LMT).

Chitosan nanoparticles of 5-fluorouracil for ophthalmic delivery: characterization, in-vitro and in-vivo study.

The aim of this investigation was to develop 5-fluorouracil (5-FU) loaded chitosan nanoparticles (CH-DNPs) for ophthalmic delivery. CH-DNPs were fabricated by ionotropic gelation mechanism using chitosan (CH) and a polyanion (TPP). The nanoparticles were smooth and spherical, confirmed by scanning electron microscopy (SEM) and atomic force microscope (AFM). CH/TPP mass ratio and TPP significantly changed the particles size morphology and encapsulation efficiency. The nanoparticles size ranged from approximately 114 to 192 nm and had a positive zeta potential (30±4 mV). The encapsulation efficiency, loading capacity and recovery of DNPs were 8.12-34.32%, 3.14-15.24% and 24.22 to 67% respectively. Physical characterization was done by Fourier transform infrared (FT-IR) and X-ray diffraction (XRD). No interaction was observed in between drug and polymer and crystallinity of drug was not changed in drug loaded nanoparticles. In-vitro release study of DNPs showed diffusion controlled release. Bioavailability study of batch CS9 was studied in rabbit eye and compare to 5-FU solution. 5-FU level was significantly higher in aqueous humor of rabbit eye. Ocular tolerance was studied in the eye of New Zealand rabbits and tested formulation was non-irritant with no sign of inflammation.

Effect of penetration enhancers on the transdermal delivery of bupranolol through rat skin.

Bupranolol (BPL) is a suitable drug candidate for transdermal drug delivery system development based on its favorable physicochemical and pharmacokinetic properties. The effect of different penetration enhancers on the permeation of BPL across rat skin was studied using side-by-side diffusion cells. 2-Pyrrolidone (PY), 1-methyl-2-pyrrolidone (MPY), and propylene glycol (PG) at various concentrations were used as penetration enhancers along with 0.4% w/v aqueous suspension of BPL. Menthol at different concentrations in isopropanol-water (6:4) mixture also was used as an enhancer wherein BPL at 0.4% w/v was completely solubilized. Skin pretreatment studies were carried out with all the above enhancers to understand their role in the penetration enhancement effect. PY and MPY at 5% w/v concentrations increased the permeation of BPL by 3.8- and 2.4-fold, respectively, versus control (p < .01). PG at 10% and 30 w/v concentrations increased the flux of BPL by 2.5- and 5.0-fold, respectively, versus control (p < .001). Menthol at 2% w/v concentration increased the flux of BPL by 3.8-fold (p < .01) and further increase in menthol concentration significantly decreased the flux of BPL. Overall, pyrrolidones and menthol at low concentrations (5% w/v or less) and PG at 30% w/v concentration were effective as penetration enhancers for BPL.

In vitro and in vivo evaluation of the Gelrite gellan gum-based ocular delivery system for indomethacin.

The poor bioavailability and therapeutic response exhibited by the conventional ophthalmic solutions due to pre-corneal elimination of the drug may be overcome by the use of in situ gel forming systems, which upon instillation as drops into the eye undergo a sol-gel transition in the cul-de-sac. This may result in better ocular availability of the drug. The purpose of this work was to develop an ophthalmic delivery system of the NSAID indomethacin, based on the concept of ion activated in situ gelation. Gelrite gellan gum, a novel ophthalmic vehicle, which gels in the presence of mono or divalent cations present in the lacrimal fluid, was used as the gelling agent. The developed formulations were therapeutically efficacious (in a uveitis induced rabbit eye model) and provided sustained release of the drug over an 8-hour period in vitro.