Human Serum Albumin, a Suitable Candidate to Stabilize Freeze-Dried IgG in Combination with Trehalose: Central Composite Design.

Freeze-dried immunoglobulin G (IgG) incorporating trehalose and human serum albumin (HSA) was statistically evaluated regarding the existence of synergism between additives on the stability profile. The levels of HSA (X) and trehalose (X) were independent variables. Aggregation following the process (Y), after 2 and 3 months at 40°C (Y) and (Y), respectively, along with the rate constant of aggregation (Y) were dependent variables.

Respiratory Administration of Infliximab Dry Powder for Local Suppression of Inflammation.

The airways are verified as a relevant route to improve antibody therapeutic index with superior lung concentration but limited passage into systemic blood stream. The current research aimed to process spray-dried (SD) powder of Infliximab to assess the feasibility of respiratory delivery of antibody for local suppression of lung-secreted tumor necrosis factor α (TNFα). Molecular and structural stability of powders were determined through size exclusion chromatography (SEC-HPLC) and Fourier transform infrared (FTIR) spectroscopy.

The effect of excipients on the stability and aerosol performance of salmon calcitonin dry powder inhalers prepared via the spray freeze drying process.

Spray freeze drying was developed to produce dry powders suitable for applications such as inhalation delivery. In the current study, the spray freeze drying technique was employed to produce inhalable salmon calcitonin microparticles. Effects of the carrier type, concentration of hydroxyl propyl-β-cyclodextrin and the presence of Tween 80 on the chemical and structural stability, as well as on the aerosol performance of the particles were investigated.

A comparative study on the physicochemical and biological stability of IgG1 and monoclonal antibodies during spray drying process.

Background: The main concern in formulation of antibodies is the intrinsic instability of these labile compounds. To evaluate the physicochemical stability of antibody in dry powder formulations, physical stability of IgG1 and a monoclonal antibody (trastuzumab) during the spray drying process was studied in a parallel study and the efficacy of some sugar based excipients in protection of antibodies was studied.

Results: The SDS-PAGE analysis showed no fragmentation of antibodies after spray drying in all formulations.

The effective encapsulation of a hydrophobic lipid-insoluble drug in solid lipid nanoparticles using a modified double emulsion solvent evaporation method.

Raloxifene HCl (RH), a selective estrogen receptor modulator (SERM), is indicated for the prophylaxis or treatment of postmenopausal osteoporosis. RH shows extremely poor bioavailability due to limited solubility and an extensive intestinal/hepatic first-pass metabolism. Solid lipid nanoparticles (SLNs) are valuable carriers that can enhance drug bioavailability.

Drying of a plasmid containing formulation: chitosan as a protecting agent.

Background: Along with research on development of more efficient gene delivery systems, it is necessary to search on stabilization processes to extend their active life span. Chitosan is a nontoxic, biocompatible and available gene delivery carrier. The aim of this study was to assess the ability of this polymer to preserve transfection efficiency during spray-drying and a modified freeze-drying process in the presence of commonly used excipients.

Preparation and evaluation of inhalable itraconazole chitosan based polymeric micelles.

Background: This study evaluated the potential of chitosan based polymeric micelles as a nanocarrier system for pulmonary delivery of itraconazole (ITRA).

Methods: Hydrophobically modified chitosan were synthesized by conjugation of stearic acid to the hydrophilic depolymerized chitosan. FTIR and 1HNMR were used to prove the chemical structure and physical properties of the depolymerized and the stearic acid grafted chitosan.

Drying of a plasmid containing formulation: chitosan as a protecting agent.

Background: The purpose of the study. Along with research on development of more efficient gene delivery systems, it is necessary to search on stabilization processes to extend their active life span. Chitosan is a nontoxic, biocompatible and available gene delivery carrier.

Stability studies of chitosan-DNA-FAP-B nanoparticles for gene delivery to lung epithelial cells.

A successful gene delivery system requires efficiency and stability during storage. Stability studies are imperative for nanomedicines containing biotechnological products such as plasmids and targeting peptides. Chitosan-DNA-FAP-B nanoparticles are novel non-viral vectors for specific gene delivery to the lung epithelial cells.

Loading hydrophilic drug in solid lipid media as nanoparticles: statistical modeling of entrapment efficiency and particle size.

Solid lipid nanoparticle (SLN) is a very well tolerated carrier systems for dermal application due to the employment physiological and/or biodegradable lipids. The effects of five factors, two categorical and three quantitative factors, were studied on the mean diameter and entrapment efficiency of the produced SLNs using response surface method (RSM), D-optimal design. Two methods of microemulsion and solvent diffusion and two types of lipid, cetyl palmitate and stearic acid, were examined comparatively.

Design, modeling, and expression of erythropoietin cysteine analogs in Pichia pastoris: improvement of mean residence times and in vivo activities through cysteine-specific PEGylation.

In this study, the low-cost production of recombinant human erythropoietin cysteine analogs (Cys-rhEPOs) from Pichia pastoris and the potential to increase their serum residency and in vivo activity through cysteine-specific PEGylation were investigated. Three-dimensional structures of several Cys-rhEPOs were generated using homology modeling, and three stable Cys-rhEPOs were selected on the basis of model stability in molecular dynamics simulation and surface accessibility of the inserted cysteine. cDNAs encoding Cys-rhEPOs were constructed by site-directed mutagenesis and expressed as secreted proteins in flask cultures of P.

Evaluation of bioactivity and pharmacokinetic characteristics of PEGylated P.pastoris-expressed erythropoietin.

High costs of production and relatively short serum half-life of mammalian cell-derived recombinant human erythropoietin (rHuEpo) necessitate finding and developing superior hosts/technologies for more efficient production of longer-acting erythropoietic agents. With these aims, we provide the first report on reductive alkylation of low-cost P.pastoris-expressed rHuEpo (PPEpo) with PEG-aldehyde.

Delivery of a cocktail DNA vaccine encoding cysteine proteinases type I, II and III with solid lipid nanoparticles potentiate protective immunity against Leishmania major infection.

Earlier generations of Leishmania vaccines have reached the third-phase of clinical trials, however none of them have shown adequate efficacy due to lack of an appropriate adjuvant. In this study, cationic solid lipid nanoparticles (cSLNs) were used to formulate three pDNAs encoding L. major cysteine proteinase type I (cpa), II (cpb) and III (cpc).

Entrapment of 5-fluorouracil into PLGA matrices using supercritical antisolvent processes.

Objectives: Two different supercritical antisolvent processes were performed to co-precipitate 5-fluorouracil (5-FU) and poly(lactide-co-glycolide) simultaneously. 5-FU is a hydrophilic antitumor agent, and is more effective when administered at a lower dose for a longer period of time.

Methods: Controlled-release polymeric systems of 5-FU were produced, and morphology, thermal behavior, in-vitro release and cytotoxicity of microparticles were analysed.

High Expression of Methylotrophic Yeast-Derived Recombinant Human Erythropoietin in a pH-Controlled Batch System.

To accomplish the worldwide demand for recombinant human erythropoietin (rHuEpo) as a therapeutic, application of cost-efficient expression system of methylotrophic yeast Pichia pastoris (P. pastoris) rather than mammalian cells is indispensable. Herein, a report on high levels secreted-expression of Pichia-derived rHuEpo by batch fermentation in a pH stabilized format is presented.

Formulation and in vitro evaluation of ciprofloxacin containing niosomes for pulmonary delivery.

In order to develop a niosome-encapsulated ciprofloxacin (CPFX) HCl formulation for pulmonary delivery, the feasibility of encapsulation of CPFX in niosomes, its stability and nebulization capability was evaluated. Various combinations of nonionic surfactants with cholesterol were used to prepare the formulations. The in vitro deposition data of the niosomal formulations were examined using an Andersen cascade impactor.

The effect of formulation variables on the characteristics of insulin-loaded poly(lactic-co-glycolic acid) microspheres prepared by a single phase oil in oil solvent evaporation method.

Biodegradable polymeric microspheres are ideal vehicles for controlled delivery applications of drugs, peptides and proteins. Amongst them, poly(lactic-co-glycolic acid) (PLGA) has generated enormous interest due to their favorable properties and also has been approved by FDA for drug delivery. Insulin-loaded PLGA microparticles were prepared by our developed single phase oil in oil (o/o) emulsion solvent evaporation technique.

An efficient biosurfactant-producing bacterium Pseudomonas aeruginosa MR01, isolated from oil excavation areas in south of Iran.

A bacterial strain was isolated and cultured from the oil excavation areas in tropical zone in southern Iran. It was affiliated with Pseudomonas. The biochemical characteristics and partial sequenced 16S rRNA gene of isolate, MR01, was identical to those of cultured representatives of the species Pseudomonas aeruginosa.

Intranasal bioavailability of insulin from carbopol-based gel spray in rabbits.

The purpose of this study was to investigate the nasal absorption of insulin from a carbopol-based nasal gel spray in rabbits. An insulin nasal gel was prepared by dispersing carbopol in distilled water, followed by the addition of insulin solution, then neutralization and viscosity adjustment. The nasal absorption of insulin from the gel, in conscious rabbits, was evaluated in comparison with absorption from an insulin solution.

Development and physical characterization of sorbitan monoester niosomes for insulin oral delivery.

Niosomes of sorbitan monoesters (Span 20, 40, 60, and 80) were prepared using the film hydration method without sonication. Unlike the other surfactants, Span 80 did not form niosomes in the absence of a sufficient amount of cholesterol. The size of vesicles depended on the cholesterol molar ratio or charge incorporation.

A rapid and sensitive method for simultaneous determination of insulin and A21-desamido insulin by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatography (RP-HPLC) method with UV-detection at room temperature has been developed for the analysis of insulin and its main degradation product, A21-desamido insulin. Octadecylsilica was used as stationary phase and a mixture of water and acetonitrile containing tetrametylammonium hydroxide as eluent. The method produced linear response over the concentration range of 10-100 microg/ml, with an average accuracy of 97.