Formulation and characterization of 5-Fluorouracil enteric coated nanoparticles for sustained and localized release in treating colorectal cancer

5-Fluorouracil is used in the treatment of colorectal cancer along with oxaliplatin as first line treatment, but it is having lack of site specificity and poor therapeutic effect. Also toxic effects to healthy cells and unavailability of major proportion of drug at the colon region remain as limitations. Toxic effects prevention and drug localization at colon area was achieved by preparing enteric-coated chitosan polymeric nanoparticles as it can be delivered directly to large bowel. Enteric coating helps in preventing the drug degradation at gastric pH. So the main objective was to prepare chitosan polymeric nanoparticles by solvent evaporation emulsification method by using different ratios of polymer (1:1, 1:2, 1:3, 1:4). Optimized polymer ratio was characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), entrapment efficiency and particle size and further subjected to enteric coating. In vitro drug release studies were done using dialysis bag technique using simulated fluids at various pH (1.2, 4.5, 7.5, 7.0) to mimic the GIT tract. 5-FU nanoparticles with drug: polymer ratio of 1:2 and 1:3 has shown better particle size (149 ± 1.28 nm and 138 ± 1.01 nm respectively), entrapment efficiency (48.12 ± 0.08% and 69.18 ± 1.89 respectively). 5-FU E1 has shown better drug release after 4 h and has shown 82% drug release till 24 h in a sustained manner comparable to the non-enteric coated tablets, which released more than 50% of the drug before entering the colon region. So we can conclude that nanoparticles prepared by this method using the same polymer with the optimized ratio can represent as potential drug delivery approach for effective delivery of the active pharmaceutical ingredient to the colorectal tumors.     

Celecoxib Incorporated Chitosan Microspheres: In Vitro and In Vivo Evaluation

Recently, considerable interest has been focussed on the use of biodegradable polymers for specialized applications such as controlled release of drug formulations; meanwhile, microsphere drug delivery systems using various kinds of biodegradable polymers have been studied extensively during the past two decades. In the present investigation, it was aimed to prepare microsphere formulations of celecoxib using a natural polymer, chitosan as a carrier for intra-articular administration to extend the retention of the drug in the knee joint. Microsphere formulations were evaluated in vitro for particle size, entrapment efficiency, surface morphology and in vitro drug release. For in vivo studies, ^99mTechnetium- labeled glutathione was used as a radiopharmaceutical to demonstrate arthritic lesions by gamma scintigraphy. Evaluation of arthritic lesions post therapy in rats showed a significant difference (P<0.05) in the group treated with celecoxib solution compared to the group treated with celecoxib loaded chitosan microspheres.     

Celecoxib incorporated chitosan microspheres: in vitro and in vivo evaluation

Recently, considerable interest has been focussed on the use of biodegradable polymers for specialized applications such as controlled release of drug formulations; meanwhile, microsphere drug delivery systems using various kinds of biodegradable polymers have been studied extensively during the past two decades. In the present investigation, it was aimed to prepare microsphere formulations of celecoxib using a natural polymer, chitosan as a carrier for intra-articular administration to extend the retention of the drug in the knee joint. Microsphere formulations were evaluated in vitro for particle size, entrapment efficiency, surface morphology and in vitro drug release. For in vivo studies, (99m)Technetium- labeled glutathione was used as a radiopharmaceutical to demonstrate arthritic lesions by gamma scintigraphy. Evaluation of arthritic lesions post therapy in rats showed a significant difference (P < 0.005) in the group treated with celecoxib solution compared to the group treated with celecoxib loaded chitosan microspheres.     

Formulation and optimization of coated PLGA – Zidovudine nanoparticles using factorial design and in vitro in vivo evaluations to determine brain targeting efficiency

In the current study zidovudine loaded PLGA nanoparticles were prepared, coated and further investigated for its effectiveness in brain targeting. IR and DSC studies were performed to determine the interaction between excipients used and to find out the nature of drug in the formulation. Formulations were prepared by adopting 2³ factorial designs to evaluate the effects of process and formulation variables. The prepared formulations were subjected for in vitro and in vivo evaluations. In vitro evaluations showed particle size below 100 nm, entrapment efficiency of formulations ranges of 28–57%, process yield of 60–76% was achieved and drug release for the formulations were in the range of 50–85%. The drug release from the formulations was found to follow Higuchi release pattern, n–value obtained after Korsemeyer plot was in the range of 0.56–0.78. In vivo evaluations were performed in mice after intraperitoneal administration of zidovudine drug solution, uncoated and coated formulation. Formulation when coated with Tween 80 achieved a higher concentration in the brain than that of the drug in solution and of the uncoated formulation. Stability studies indicated that there was no degradation of the drug in the formulation after 90 days of preparation when stored in refrigerated condition.     

Stealth Amphotericin B nanoparticles for oral drug delivery: In vitro optimization

Purpose

Amphotericin B (AmB) is an effective anti-fungal and anti-leishmanial agent. However, AmB has low oral bioavailability (0.3%) and adverse effects (e.g., nephrotoxicity). The objectives of this study were to improve the oral bioavailability by entrapping AmB in pegylated (PEG) poly lactide co glycolide copolymer (PLGA–PEG) nanoparticles (NPs). The feasibility of different surfactants and stabilizers on the mean particle size (MPS) and entrapment efficiency were also investigated.

Materials and methods

NPs of AmB were prepared by a modified emulsification diffusion method employing a vitamin E derivative as a stabilizer. Physicochemical properties and particle size characterization were evaluated using Fourier Transform Infra-Red spectroscopy (FTIR), differential scanning calorimetry, scanning electron microscopy and transmission electron microscopy. Moreover, in vitro dissolution profiles were performed for all formulated AmB NPs.

Results

MPS of the prepared spherical particles of AmB ranged from 26.4 ± 2.9 to 1068 ± 489.8 nm. An increased stirring rate favored AmB NPs with a smaller MPS. There was a significant reduction in MPS, drug content and drug release, when AmB NPs were prepared using the diblock polymer PLGA–PEG with 15% PEG. Addition of three emulsifying agents poly vinyl pyrrolidone (PVP), Vitamin E (TPGS) and pluronic F-68 to AmB formulations led to a significant reduction in particle size and increase in drug entrapment efficiency (DEE) compared to addition of PVP alone. FTIR spectroscopy demonstrated a successful loading of AmB to pegylated PLGA–PEG copolymers. PLGA–PEG copolymer entrapment efficiency of AmB was increased up to 56.7%, with 92.7% drug yield. After a slow initial release, between 20% and 54% of AmB was released in vitro within 24 h phosphate buffer containing 2% sodium deoxycholate and were best fit Korsmeyer–Peppas model. In conclusion, PLGA–PEG diblock copolymer with 15% PEG produced a significant reduction (>70%) in MPS with highest drug content. The percentage of PEG in the copolymer and the surfactant/stabilizer used had a direct effect on AmB release in vitro, entrapment efficiency and MPS. These developed formulations are feasible, effective and improved alternatives to other carriers for oral delivery of AmB.     

Calcipotriol delivery into the skin as emulgel for effective permeation

The objective of this work is to formulate and evaluate an emulgel containing calcipotriol for treatment of psoriasis. Emulgels have emerged as a promising drug delivery system for the delivery of hydrophobic drugs. Isopropyl alcohol and polyethylene glycol have been employed as permeation enhancers. Formulation chart is made with seven formulations, evaluated for physical parameters, drug content, viscosity, thixotropy, spreadability, extrudability, mucoadhesion, diffusion studies, skin irritation test along with short term stability studies. Carbopolis is reported to have a direct influence on appearance and viscosity of final formulation. The photomicroscopic evaluations showed the presence of spherical globules in size range of 10–15 μm. Rheograms revealed that all the formulations exhibited pseudoplastic flow. Optimized formulation (F6) had shown 86.42 ± 2.0% drug release at the end of 8 h study. The release rate through dialysis membrane and rat skin is higher when compared to commercial calcipotriol ointment. Hence it is concluded that calcipotriol can be delivered topically with enhanced penetration properties when formulated as emulgel.     

SEDDS of gliclazide: Preparation and characterization by in-vitro,ex-vivo and in-vivo techniques

In the study, self emulsifying drug delivery system (SEDDS) of gliclazide, a poorly soluble drug, was developed and evaluated by in-vitro, ex-vivo and in-vivo techniques. Oil and surfactant were screened out according to their solubilizing capacity. Among the tested components Transcutol HP and Tween-80 showed good solubilizing capacity. These two components were used in different ratios to prepare gliclazide SEDDS. The SEDDS formulations were transparent and clear. Droplet size of the emulsion was determined by Laser Diffraction Technology of Malvern. Formulation F1 containing 1:1 (m/m) mixture of Transcutol HP/Tween-80 showed minimum mean droplet size (50.959 μm). In-vitro drug release from F1 was higher (99% within 20 min) than other formulations. The developed SEDDS was also evaluated for ex-vivo permeability profile by using chicken intestinal sac. Formulation F1 showed optimal drug diffusion. In-vivo performance of SEDDS was evaluated in albino mice using plasma glucose level as a pharmacodynamic marker parameter. The test formulation (F1) showed significant reduction in plasma glucose level, after oral administration. So SEDDS may be an alternative technique for the oral administration of gliclazide.     

Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression

The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (∼24 h) and metformin (∼8–12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct compression.     

Multiparticulate System for Colon Targeted Delivery of Ondansetron

Targeted delivery of drugs to colon has the potential for local treatment of a variety of colonic diseases. The main objective of the study was to develop a multiparticulate system containing chitosan microspheres for the colon targeted delivery of ondansetron for the treatment of irritable bowel syndrome. This work combines pH-dependent solubility of eudragit S-100 polymers and microbial degradability of chitosan polymers. Chitosan microspheres containing ondansetron were prepared by emulsion cross linking method. The effect of process variables like chitosan concentration, drug-polymer ratio, emulsifier concentration and stirring speed were studied on particle size and entrapment efficiency of chitosan microspheres. In vitro drug release studies in simulated gastro intestinal fluids showed a burst drug release pattern in the initial hour necessitating microencapsulation around the chitosan microspheres. The optimized formulation was then subjected to microencapsulation with eudragit S-100 by solvent evaporation technique. The effect of different coat/core ratio on particle size, drug entrapment efficiency and in vitro drug release were studied. Formulation which contain 1:10 core/coat ratio released lesser amount of drug in the upper gastro intestinal conditions and so selected as best formulation and then subjected to in vitro drug release studies in presence of rat ceacal contents to assess biodegradability of chitosan microspheres in colon. In order to study the drug release mechanism in vitro drug release data was fitted into various kinetic models. Analysis of regression values suggested that the possible drug release mechanism was Peppas model.     

Dissolution of Commercially Available Mesalamine Formulations at Various pH Levels

Introduction

Mesalamine (5-aminosalicylic acid; 5-ASA) is recommended first-line therapy for mild-to-moderate ulcerative colitis. Many mesalamine formulations employ a pH-dependent release mechanism designed to maximize drug release in the colon. This study compared the in vitro release of 5-ASA from six commercially available mesalamine formulations at pH levels similar to those typically encountered in the human gastrointestinal tract.

Methods

The release of 5-ASA from six mesalamine formulations [Mesalazin-Kohlpharma (Kohlpharma, Germany), Mesalazin-Eurim (Eurimpharm, Germany), Mesalazina-Faes (Faes Farma, Spain), Mesalazine EC (Actavis B.V., Netherlands), Mesalazine EC 500 PCH (Pharmachemie B.V., Netherlands); multimatrix mesalamine (Shire US Inc., USA)] was monitored separately at three different pH levels [1.0 (2 h), 6.4 (1 h), and 7.2 (8 h)] using United States Pharmacopeia dissolution apparatus II. The dissolution percentage was calculated as a mean of 12 units for each formulation.

Results

At pH 1.0 and 6.4, <1 % of 5-ASA release was observed for each of the mesalamine formulations tested. At pH 7.2, complete release of 5-ASA occurred within 1 h for Mesalazine EC and Mesalazine EC 500 PCH, and within 2 h for Mesalazin-Kohlpharma, Mesalazin-Eurim, and Mesalazina-Faes; complete release of 5-ASA from multimatrix mesalamine occurred within 7 h. Little variability in rate of 5-ASA dissolution was observed between tablets of each formulation.

Conclusion

At pH 7.2, 5-ASA release profiles were variable among the commercially available mesalamine formulations that were tested.     

Solid lipid nanoparticles for nose to brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation

In the present study, haloperidol (HP)-loaded solid lipid nanoparticles (SLNs) were prepared to enhance the uptake of HP to brain via intranasal (i.n.) delivery. SLNs were prepared by a modified emulsification–diffusion technique and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release, and stability. All parameters were found to be in an acceptable range. In vitro drug release was found to be 94.16±4.78% after 24 h and was fitted to the Higuchi model with a very high correlation coefficient (R²=0.9941). Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography. The brain/blood ratio at 0.5 h for HP-SLNs i.n., HP sol. i.n. and HP sol. i.v. was 1.61, 0.17 and 0.031, respectively, indicating direct nose-to-brain transport, bypassing the blood–brain barrier. The maximum concentration (C_max) in brain achieved from i.n. administration of HP-SLNs (329.17±20.89 ng/mL, T_max 2 h) was significantly higher than that achieved after i.v. (76.95±7.62 ng/mL, T_max 1 h), and i.n. (90.13±6.28 ng/mL, T_max 2 h) administration of HP sol. The highest drug-targeting efficiency (2362.43%) and direct transport percentage (95.77%) was found with HP-SLNs as compared to the other formulations. Higher DTE (%) and DTP (%) suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations.KEY WORDS: Brain targeting, Haloperidol, Intranasal route, Pharmacokinetics, Solid lipid nanoparticles     

Ketorolac tromethamine floating beads for oral application: Characterization and in vitro/in vivo evaluation

The floating beads have been employed to make a sustained release of the drug in the stomach and to decrease the dose of the drug and hence overcome its side effects. The common benefits of the floating beads were it is easy preparation, without the need of a high temperature, and high percentage of the drug entrapment. In the present work, the Ketorolac tromethamine (KT) floating beads were prepared by extrusion congealing method utilizing calcium carbonate as a gas forming agent. The physical characters of the produced beads were investigated such as KT yield, KT loading, and entrapment efficiency of the drug. In addition, floating behavior, swelling, particle size, morphology and KT stability were also evaluated. In vitro drug release study was carried out, and the kinetics of the release was evaluated using the linear regression method. Furthermore, the in vivo analgesic effect of KT after oral administration of the selected formula of floating beads (F10) was carried out using hot plate and tail flick methods. Oral commercial KT tablets and KT solution were used for the comparison. The prepared beads remained floated for more than 8 h. The optimized formulation (F10) exhibited prolonged drug release (more than 8 h) and the drug release follows the Higuchi kinetic model, with a Fickian diffusion mechanism according to Korsmeyer-Peppas (n = 0.466). Moreover, F10 showed a sustained analgesic effect as compared to the commercial tablet.     

Preparation and evaluation of zinc-pectin-chitosan composite particles for drug delivery to the colon: role of chitosan in modifying in vitro and in vivo drug release

Zinc-pectin-chitosan composite microparticles were designed and developed as colon-specific carrier. Resveratrol was used as model drug due to its potential activity on colon diseases. Formulations were produced by varying different formulation parameters (cross-linking pH, chitosan concentration, cross-linking time, molecular weight of chitosan, and drug concentration). Single-step formulation technique was compared with multi-step technique. Effect of these parameters was investigated on shape, size, weight, weight loss (WL), moisture content (MC), encapsulation efficiency (EE), drug loading (L), and drug release pattern of the microparticles. The formulation conditions were optimized from the drug release study. In vivo pharmacokinetics of the zinc-pectinate particles was compared with the zinc-pectin-chitosan composite particles in rats. Formulations were spherical with 920.48-1107.56 μm size, 21.19-24.27 mg weight of 50 particles, 89.83-94.34% WL, 8.31-13.25% MC, 96.95-98.85% EE, and 17.82-48.31% L. Formulation parameters showed significant influence on drug release pattern from the formulations. Formulation prepared at pH 1.5, 1% chitosan, 120 min cross-linking time, and pectin:drug at 3:1 ratio demonstrated colon-specific drug release. Microparticles were stable at 4 °C and room temperature. Pharmacokinetic study indicated in vivo colon-specific drug release from the zinc-pectin-chitosan composite particles only.     

Comparative study of some biodegradable polymers on the entrapment efficiency and release behavior of etoposide from microspheres

Etoposide-loaded biodegradable microspheres of poly lactic-co-glycolide (PLGA) 50:50, PLGA 75:25, and polycaprolactone (PCL) were prepared by simple o/w emulsification solvent evaparation method and characterized by size analysis and microscopy. The influence of drug to polymer ratio on the entrapment of etoposide was studied. Of all the three types of microspheres, polycaprolactone microspheres (PCL MS) showed the highest entrapment efficiency (94.64%), followed by PLGA 75:25 microspheres (PLGA 75:25 MS) (88.64%) and PLGA 50:50 microspheres (PLGA 50:50 MS) (79.19%). The drug to polymer ratio of 1:20 gave the highest entrapment efficiency for all the three types of microspheres. The in vitro release of etoposide from the three microsphere formulations were studied in phosphate buffer pH 7.4 (pH 7.4 PB) containing 0.1% Tween 80. The microspheres showed an initial burst release, which was highest from the PLGA 50:50 MS and least from the PCL MS. PCL MS microspheres showed the lower and slow drug release than the remaining formulations. The release of etoposide from all the three microsphere formulations followed Higuchi's diffusion pattern. The microspheres in the dissolution medium for 28 days appeared irregular in shape and slightly fragmented.     

Preparation and characterization of free mixed-film of pectin/chitosan/Eudragit RS intended for sigmoidal drug delivery.

Polyelectrolyte complex (PEC) film between pectin as an anionic polyelectrolyte and chitosan as a cationic species was prepared by blending two polymer solutions at weight ratio of 2:1 and then solvent casting method. Besides pectin/chitosan PEC film, Eudragit RS, pectin/Eudragit RS and pectin/chitosan/Eudragit RS films were also prepared by aforementioned method. In mixed-film formulations, a fixed weight ratio of 1:5 of pectin or pectin/chitosan complex to Eudragit RS was used. Characterizations of pectin/chitosan interaction in solution were investigated by turbidity and viscosity measurement and in the solid state by Fourier transform infrared (FTIR) spectroscopy, wide angle X-ray diffraction (WAXRD) and thermogravimetric analysis (TGA). It was observed that the swelling profile of pectin/chitosan film was pH-dependent and its swelling ratio in phosphate buffer solution (PBS) pH 7.4 was about 2.5-fold higher than that of PBS pH 6.0. Formulation containing only pectin/chitosan could not protect free film from high swelling in the aqueous media, therefore, Eudragit RS as a water-insoluble polymer must be included in the mixed-film. The formation of PEC between pectin and chitosan resulted in a decrease in the crystallinity and thermal stability caused by the interactions between polyions. Drug permeation or diffusion studies were carried out using Plexiglas diffusion cell consisting of donor and acceptor compartments. Theophylline was selected as a model drug to measure permeability coefficient. Drug permeation through pectin/chitosan/Eudragit RS showed a sigmoidal pattern; whereas drug diffusion through pectin/Eudragit RS and Eudragit RS films followed a linear characteristic. The drug permeation through the ternary mixed-film showed a burst release upon exposure to PBS pH 6.0. This mixed-film formulation showed the potential for sigmoidal drug delivery with an initial, controllable slow release followed by a burst release immediately after the change in pH. The burst drug permeation might possibly be due to change in film's porosity.     

Directly compressed rosuvastatin calcium tablets that offer hydrotropic and micellar solubilization for improved dissolution rate and extent of drug release

The objective was to use caffeine and Soluplus® to improve the dissolution rate and to maintain a concentration of BCS Class II rosuvastatin calcium that exceeds its solubility. Caffeine and Soluplus® together substantially improved the dissolution rate and the extent of rosuvastatin release. Formulations for direct compression tablets included Formulation F1, a control with drug but with neither caffeine nor Soluplus® present; F2 with drug-caffeine complex; F3 with drug and Soluplus® and F4 with drug-caffeine complex and Soluplus®. Each formulation blend provided satisfactory flow properties. Tablets were comparable in mass, hardness and friability. A marked decrease in disintegration time occurred when the hydrotropic or micellar agent was included in the formulation. Assay (98–100%) and content uniformity (99–100%) results met requirements. Release studies in pH 1.2, 6.6, and 6.8 buffers revealed the superiority of F4. At 45 min sampling time, F3 and F4 tablets each provided a cumulative drug release greater than 70% in each medium. F2 tablets exhibited compliance to official standards in pH 6.6 and 6.8 buffers but not in pH 1.2 buffer, whereas tablets based on F1 failed in each medium. Two-factor ANOVA of the release data revealed a statistical difference across the four formulations in each release medium. Pairwise comparison of release profiles demonstrated that, of the four formulations, F4 provided the most effectively enhanced dissolution rate, improvement to the extent of drug release and support of a concentration higher than the solubility of rosuvastatin calcium.     

Preparation of a novel floating ring capsule-type dosage form for stomach specific delivery

Study objectives were to develop a unique floating ring capsule dosage form which combines gastric soluble and insoluble portions, and to evaluate its suitability for stomach specific drug delivery. New floating ring capsules were developed using different polymers and were compared for various parameters. The formulation with HPMC and sodium CMC has better floating properties. The effects of polymers concentration on drug release were studies by in vitro release studies. The interaction studies of combined drug with polymers were determined using FT-IR spectroscopy. The entrapped air within the gel barrier and lower densities of HPMC and sodium CMC resulted in better floating behavior. Steady slow gel formations showed prolonged drug release. The in vitro release rates were generally found to be faster with low concentration of carbopol showing release within 2 h, while formulations containing high amount of HPMC showed release in 8 h. In particular, the higher concentration of HPMC formulation shows the best drug release performance. A very low change in peak shift was observed only with sodium alginate formulations. Further, FT-IR measurements confirmed the absence of any chemical interactions. Results indicate that new floating ring capsule is a promise dosage form for stomach specific delivery.     

In-vitro and in-vivo evaluation of repaglinide loaded floating microspheres prepared from different viscosity grades of HPMC polymer

During the study repaglinide encapsulated floating microspheres were formulated and characterized for enhancing residence time of drug in git and thereby increasing its bioavailability. Floating microspheres of ethylcellulose (EC) and hydroxypropyl methyl cellulose (HPMC) (5 and 100 cps) were prepared by emulsion solvent diffusion technique. During process optimization various parameters were studied such as: drug: polymer ratio, polymer ratio, concentration of emulsifier and stirring speed. Selected optimized formulations were studied for SEM, entrapment, floating behavior, drug release and kinetics. In-vivo floating ability (X-ray) study and in-vivo antidiabetic activity were performed on alloxan induced diabetic rats. Microspheres prepared with different viscosity grade HPMC were spherical shaped with smooth surface. Size of microspheres was in the range of 181.1–248 μm. Good entrapment and buoyancy were observed for 12 h. X-ray image showed that optimized formulation remained buoyant for more than 6 h. Optimized formulation treated group shows significant (p < 0.01) reduction in blood glucose level as compared to pure drug treated group. Repaglinide loaded floating microspheres expected to give new choice for safe, economical and increased bioavailable formulation for effective management of NIDDM.Abbreviations: EC, ethylcellulose; HPMC, hydroxypropyl methylcellulose; SEM, scanning electron microscopy; GRT, gastric residence time; ATP, adenosine tri phosphate; PVA, polyvinyl alcohol; PEG, polyethylene glycerol; UV, uv–visible     

Pharmacokinetic variables of medium molecular weight cross linked chitosan nanoparticles to enhance the bioavailability of 5-fluorouracil and reduce the acute oral toxicity

To prepare glutaraldehyde-based cross-linked medium molecular weight chitosan nanoparticles encapsulated with 5-Fluorouracil (5-FU), to overcome dosing frequency as well as reducing acute oral toxicity and poor bioavailability of the drug. Medium molecular weight chitosan nanoparticles (MMWCH-NPs) were prepared by reverse micelles method based on glutaraldehyde (GA) cross-linking and optimized by the process as well as formulation variables like a various drug to polymer ratio, cross-linker volumes, varying stirring speeds (rpm), different time of rotation/stirring, respectively and their effects on the mean particles size distribution and entrapment efficiency %EE and %LC of NPs. Characterization of formulations was done by FTIR studies, TEM, PXRD, TGA, Stability, and dissolution drug release studies were performed by dialysis bag technique at both pH (1.2 & 7.4) and acute oral toxicity studies in albino rabbits. The formulated nanoparticles showed a smooth morphology with smaller particle size distribution (230–550 nm), zeta potential (−15 to −18 mV) required to achieve enhanced permeation and retention effect (EPR), entrapment efficiency (%EE 12–59%). These NPs exhibited a controlled drug release profile with 84.36% of the drug over a period of 24 h. Drug release data were fitted to different kinetic models which predominantly followed Fickian diffusion mechanism (R² = 0.972–0.976, N = 0.326–0.256). The optimized formulation (5-FU6) was observed under DSC/TGA, TEM. PXRD curves, FTIR, which confirmed thermal stability, structural integrity, amorphous state, compatibility between drug and polymer of optimized (5-FU6) as well as reduced acute oral toxicity in albino rabbits. Cross-linked medium molecular weight chitosan nanoparticles are nontoxic, well-tolerated therefore could be the future candidate for therapeutic effects as novel drug delivery carrier for anticancer drug(s).     

Gemcitabine cationic polymeric nanoparticles against ovarian cancer: formulation,characterization, and targeted drug delivery

This study focused on gemcitabine (GTB) delivery of cationic polymeric nanoparticles to treat ovarian cancer in order to promote effective localized delivery and drug retention during biological discharge. To begin, four GTB-loaded polymer nanoparticles were prepared: chitosan nanoparticles (CS-NPs), polysarcosin nanoparticles (PSar-NPs), poly-l-lysine & polysarcosin nanoparticles (PLL-PSar-NPs), and chitosan & polysarcosin nanoparticles (CS-PSar-NPs). Based on preliminary particle size, zeta potential, encapsulation efficiency, DSC, surface morphology, release profiling, and cellular internalization studies using rhodamine 123 and Nile red fluorescent markers, it was hypothesized that CS-PSar-NPs could be the best cationic formulation with strong biocompatibility and anticancer activity against the OVCAR-8 ovarian cancer cell line. To improve effective targeting, cellular penetration, and in vitro cytotoxicity, epidermal growth factor receptor variation III (EGFRvIII) is attached over all four polymeric nanoparticles. Confocal imaging revealed that EGFRvIII-conjugated cationic GTB polymeric nanoparticles had a greater cellular uptake and double internalization capabilities than unconjugated nanoparticles, as well as time-dependent cell entrance. GTB and EGFRvIII-conjugated polymer nanoparticles would have a stronger potential to infiltrate ovarian cancer cells during the first hour of incubation. According to TEM and FTIR findings, EGFRvIII conjugation across the non-target CS-PSar-NP surface was successful, making CS-PSar-NPS-EGFRvIII more target-specific and thus a safer drug delivery candidate for ovarian cancer treatment.

Highlights

• GTB loaded non-target CS-PSar-NPs & active targeted CS-PSar-NPs-EGFRvII developed.
• SEM, AFM, DSC, particle size, zeta potential, internalization performed for CS-PSar-NPs.
• MTT & CLSM study confirmed CS-PSar-NPS-EGFRvII was binding specific to OVCAR-8 cells
• Fabrication of EGFRvII over nanoparticles confirmed by TEM.
• CS-PSar-NPS-EGFRvII safer candidate for ovarian cancer.