[Show abstract][Hide abstract] ABSTRACT: The poor water solubility of many candidate drugs remains a major obstacle to their development and clinical use, especially for oral drug delivery. Nanocrystal technology can improve the solubility and dissolution rates of many poorly water-soluble drugs very effectively, significantly improving their oral bioavailability and decreasing the food effect. For this reason, this technology is becoming a key area of drug delivery research. This review presents much of the recent progress in nanocrystal drug pharmaceuticals, including the characteristics, composition, preparation technology, and clinical applications of these drugs. Finally, the effect of nanocrystal technology on insoluble drugs is quantified and described.
[Show abstract][Hide abstract] ABSTRACT: Abstract Paclitaxel (PTX) is a natural broad-spectrum anticancer drug with poor aqueous solubility. PTX nanocrystals were formulated to improve the water solubility, and PTX nanosuspensions were prepared using anti-solvent precipitation, and then organic solvent and surfactants were removed by filtering through a vacuum system. The physical characterization of PTX nanocrystals were measured by transmission electron microscope, X-ray diffraction and differential scanning calorimetry. In addition, saturation solubility, in vitro release, stability and pharmacokinetic characteristics were examined. The average particle size of PTX nanocrystals was ∼200 nm, and they had a stable potential and a uniform distribution. Paclitaxel nanocrystals can effectively improve drug solubility and in vitro release. PTX pharmacokinetic and tissue distribution studies were compared after intravenous administration of nanocrystals versus a commercial injection formulation. PTX nanocrystals were rapidly distributed with a longer elimination phase. Moreover, tissue distribution indicated that PTX nanocrystals are mainly absorbed by the liver and spleen and may offer reduced renal and cardiovascular toxicity which may reduce side effects.
No preview · Article · Aug 2014 · Drug Development and Industrial Pharmacy
[Show abstract][Hide abstract] ABSTRACT: Objective:
The aim of this study was to investigate the ciprofloxacin liposome of high encapsulation efficiency with optimal physical properties for pulmonary administration and to test its in-vivo potential in rats.
Ciprofloxacin-loaded liposome was prepared by gradient of ammonium sulfate method. The particle size and morphology were determined using a NANOPHOX particle size analyzer and a transmission electron microscope, respectively. Encapsulation efficiency was calculated by UV spectrophotometry. Ciprofloxacin liposome released in vitro was performed using simulated lung fluid. In-vivo studies, pharmacokinetics and pulmonary distribution, HPLC method was established to determine the concentration of ciprofloxacin in rat plasma and lung tissue. The pulmonary pathological section was used to observe the change of pulmonary pathology.
The optimized ciprofloxacin liposome, which had a high encapsulation efficiency of 93.96%, and an average particle size of 349.6 nm with a span of 0.42, showed sustained in-vitro release. The optimized ciprofloxacin liposome was further examined in the in-vivo study in rats. The concentration of ciprofloxacin in lung and blood was simultaneously determined in each rat. The ratio of the AUClung value between ciprofloxacin liposome and ciprofloxacin solution was 288.33, whereas the relative bioavailability was 72.42%, and the drug targeting efficiency of ciprofloxacin liposome and ciprofloxacin solution by intratracheal administration were 799.71 and 2.01, respectively.
Ciprofloxacin liposome for pulmonary administration offered an attractive alternative that was able to deliver high concentrations of antibiotic directly to the chosen target site while minimizing the local irritation.
No preview · Article · Nov 2013 · Drug Development and Industrial Pharmacy
[Show abstract][Hide abstract] ABSTRACT: Context: Vasoactive intestinal peptide (VIP) is a linear cationic neuropeptide composed of 28 amino acids. It belongs to the glucagon/secretin family. The biological functions of VIP are relatively broad, but it has not been well studied in the field of pharmaceutics. Especially in the selection of the way of VIP administration and the pharmaceutical formulation, the theory basis was deficient appreciably. Objective: To provide the theory basis for the pharmaceutical development of VIP, the chemical and biological stability of VIP was studied. Materials and methods: The stability of VIP in different pH values, ionic strength, temperature, artificial gastric fluid and artificial intestinal fluid was investigated, and the concentration of VIP was calculated by HPLC method. Results: The stability of VIP was pH-dependent. VIP was stable in acid and neutral solution, and almost didn't degrade during pH ≤ 7 solution. However, it was instability in basic solution and degraded completely at 30 min in pH 13 solution. Ionic strength did not affect its stability. VIP was stable in freezing conditions but it degraded at low concentration in cold storage. Furthermore, VIP degraded so quickly in artificial gastric fluid and artificial intestinal fluid that it can't be detected at 0 min. Discussion and conclusion: the chemical and biological characteristic of VIP was unstable, so it isn't suitable for oral administration.
No preview · Article · Jun 2012 · Drug Development and Industrial Pharmacy
[Show abstract][Hide abstract] ABSTRACT: Poly(D,L-lactide-co-glycolide) nanoparticles (PLGA-NP) have been extensively used as a drug delivery system for proteins and peptides. However, their negative surface charge decreases bioavailability under oral administration. Recently, cationically modified PLGA-NP has been introduced as novel carriers for oral delivery. The characteristics of the nanoparticles, such as particle size, surface charge, and bioadhesion are considered the most significant determinants of the effect of these nanoparticles both in vitro and in vivo. Our aim was to introduce and evaluate the physiochemical characteristics, bioadhesion, and biological activity of positively charged chitosan-coated PLGA-NP (CS-PLGA-NP), using insulin as a model drug. Results were compared to those of common negatively charged PLGA-NP and the in vitro cytotoxicity of the two types of nanoparticles was examined. These results indicate that both CS-PLGA-NP and PLGA-NP had a narrow size distribution, averaging less than 150 nm. CS-PLGA-NP was positively charged (+43.1 ± 0.3 mV), exhibiting the cationic nature of chitosan, whereas PLGA-NP showed a negative surface charge (-1.72 ± 0.2 mV). CS-PLGA-NP exhibited stronger bioadhesive potency than PLGA-NP and much greater relative pharmacological availability with regard to orally delivered insulin. In addition, an evaluation of cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed no increase in toxicity in either kind of nanoparticle during the formulation process. The study proves that CS-PLGA-NP can be used as a vector in oral drug delivery systems for proteins and peptides due to its positive surface charge and bioadhesive properties.
No preview · Article · Apr 2012 · European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences