Biodegradable nanoparticulate carriers are potentially applicable compounds in the administration of therapeutic agents and drug delivery. They have received much attention due to their biological characteristics such as biodegradability, biocompatibility, and bioadhesive. The objectives of this work are first, investigating the impact of two important parameters (i.e. chitosan or sodium tripolyphosphate (TPP) solution concentration and chitosan to TPP mass ratio) on the chitosan nanoparticles (CNPs) formation by ionic-gelation method and then, the synthesis and characterization of chitosan-based, biodegradable drug-loaded nanoparticles in the encapsulation of novel 4\'-(4-(methylsulfonyl)phenyl)-3\'-(3,4,5-trimethoxyphenyl)-4\'H-spiro[indene-2,5\'-isoxazol]-1(3H)-one (MTS) indanonic tricyclic spiroisoxazoline, which is a potent anticancer drug. The particle size, shape, zeta potential, drug loading capacity, in vitro release characteristics, and stability of the formulated drug-loaded nanoparticles of the different drug:carrier ratio has been studied. The results indicated that the particle size increased at the higher chitosan or TPP concentration while the mass ratio did not appear to be a significant parameter during the cross-linking process. The particle diameter and zeta potential of CNPs including MTS were approximately in the range of 256-350 nm and 24.08-38.70 mV, respectively. The entrapment efficiency steadily increased with increasing the concentration of the polymer in formulizations. Throughout 24 h, the in vitro release behavior was provided a sustained release from all the drug-loaded formulizations. The optimal formulization of CNPs based on drug content with a drug:carrier ratio of 1:2 did not change appreciably during 60-day storage at either 4 °C or the ambient temperature.

UNASSIGNED: The purpose of this study was to investigate the effect of andrographolide-carboxymethyl chitosan nanoparticles formation on the physical characteristics, in vitro release profile and in vivo antimalarial activity of andrographolide.
UNASSIGNED: Nanoparticles were prepared by ionic gelation method-spray drying using CaCl2 as the crosslinker with a composition of drug: polymer: CaCl2=40: 250: 100. The obtained particles were evaluated for its size and morphology; physical state, drug content, in vitro drug release and in vivo antimalarial activity on Plasmodium berghei infected mice.
UNASSIGNED: The results of DTA and XRD showed that nanoparticle systems had a lower melting point and lower crystallinity degree. The drug dissolved from the nanoparticles was increased up to 6.5 times and the in vivo antimalarial activity was 1.65 times higher compared to andrographolide.
UNASSIGNED: The formation andrographolide-carboxymethyl chitosan nanoparticles affected the physical characte-ristics of andrographolide. The decrease crystallinity of andrographolide resulted in a lower melting point of andrographolide. Such changes provided a positive impact to the drug dissolution and then its activity.

The main objective of this study was to evaluate the most suitable conditions to prepare 5-fluorouracil (5-FU) loaded chitosan nanoparticles (CSNPs). 5-FU loaded CSNPs were prepared employing the ionic gelation technique using three different molecular weights of CS with the polyanion sodium tripolyphosphate (STPP) as cross-linking agent. The preparation was based on the ionic interaction of positively charged CS and negatively charged STPP. The entrapment efficiency (EE%) of CSNPs was in the range of 3.86-21.82% EE% exhibited a clear increase with increasing CS concentration. The averge particles size was in the nanosize range and monodisperse in nature whereas transmission electron microscope micrographs showed that the prepared nanoparticles have a spherical shape. Fourier transform infrared (FTIR), X- ray differaction (XRD) and differential scanning calorimetry (DSC) confirmed successful incorporation of 5-FU in prepared CSNPs. In vitro release of 5-FU from selected formulations exhibited sustained release from the nanoparticles where slower release was observed when higher molecular weight CS was used. The study of drug release kinetics revealed that the release of 5-FU from CSNPs followed a diffusion controlled pattern.

BACKGROUND: The purpose of this study was to formulate, characterize and in-vitro cytotoxicity of 5-Fluorouracil loaded controlled release nanoparticles for the treatment of skin cancer. The patents on nanoparticles (US8414926B1), (US61654404A), (WO2007150075A3) etc. helped in the selection polymers and method for the preparation of nanoparticles.
METHODS: In the present study nanoparticles were prepared by simple ionic gelation method using various concentrations of chitosan and sodium tripolyphosphate (TPP). Several process and formulation parameters were screened and optimized using 25-2 fractional factorial design. The prepared nanoparticles were evaluated for particle size, shape, charge, entrapment efficiency, crosslinking mechanism and drug release study.
RESULTS: The optimized 5-Fluorouracil loaded nanoparticle were found with particle size of of 320±2.1 nm, entrapment efficiency of 85.12%± 1.1% and Zeta potential of 29mv±1mv. Scanning electron microscopy and dynamic light scattering technique revealed spherical particles with uniform size. The invitro release profile showed controlled release up to 24 hr. Further study was carried using A375 basal cell carcinoma cell-line to elucidate the mechanism of its cytotoxicity by MTT assay.
CONCLUSIONS: These results demonstrate that the possibility of delivering 5-Fluorouracil to skin with enhanced encapsulation efficiency indicating effectiveness of the formulation for treatment of basal cell carcinoma type of skin cancer.

In this study, an attempt was made to develop bi-functional constructs serving both as scaffolds and potential delivery systems for application in neural tissue engineering. The constructs were prepared in two steps. In the first step, the bulks of poly (L-lactic acid) (PLLA) in 1, 4-dioxane/water (87:13) were fabricated using liquid-liquid thermally induced phase separation technique. In the next step, the prepared bulks were coated with chitosan nanoparticles produced by two different techniques of ultrasonication and ionic gelation by grafting-coating technique. In ultrasonication technique, the chitosan solution (2 mg/mL) in acetic acid/sodium acetate buffer (90:10) was irradiated by an ultrasound generator at 20 kHz and power output of 750 W for 100 s. In ionic gelation technique, the tripolyphosphate in water solution (1 mg/mL) was added to the same chitosan solution. The physicochemical properties of the products were characterized by Scanning Electron Microscopy, Attenuated Total Reflection Fourier Transform-Infrared, liquid displacement technique, contact angle measurement, compressive and tensile tests, as well as zeta potential and particle size analysis using dynamic light scattering. Moreover, the cell proliferation and attachment on the scaffolds were evaluated through human glioblastoma cell line (U-87 MG) and human neuroblastoma cell line [BE (2)-C] culture respectively. The results showed that the samples coated with chitosan nanoparticles prepared by ultrasonication possessed enhanced hydrophilicity, biodegradation and cytocompatibility compared with pure PLLA and PLLA coated with chitosan nanoparticles prepared by ionic gelation. This study suggests successful nanoparticles-scaffold systems which can act simultaneously as potential delivery systems and tissue engineering scaffolds.

Nanoparticles have proven to be an effective delivery system with few side effects for anticancer drugs. In this study, gemcitabine-loaded nanoparticles have been prepared by an ionic gelation method using chitosan and Pluronic(®) F-127 as a carrier. Prepared nanoparticles were characterized using dynamic light scattering, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), scanning electron microscopy, and transmission electron microscopy. Different parameters such as concentration of sodium tripolyphosphate, chitosan, Pluronic, and drug on the properties of the prepared nanoparticles were evaluated. In vitro drug release was studied in phosphate-buffered saline (PBS; pH = 7.4). The cytotoxicity of the nanoparticles was assayed in the HT-29 colon cancer cell line. The mucoadhesion behavior of the nanoparticles was also studied by mucus glycoprotein assay. The prepared nanoparticles had a spherical shape with positive charge and a mean diameter ranging between 80 to 170 nm. FT-IR and DSC studies found that the drug was dispersed in its amorphous form due to its potent interaction with nanoparticle matrix. Maximum drug encapsulation efficiency was achieved at 0.4 mg/mL gemcitabine while maximum drug loading was 6% obtained from 0.6 mg/mL gemcitabine. An in vitro drug release study at 37°C in PBS (pH = 7.4) exhibited a controlled release profile for chitosan-Pluronic(®) F-127 nanoparticles. A cytotoxicity assay of gemcitabine-loaded nanoparticles showed an increase in the cytotoxicity of gemcitabine embedded in the nanoparticles in comparison with drug alone. The mucoadhesion study results suggest that nanoparticles could be considered as an efficient oral formulation for colon cancer treatment.