Funderwulff3168

Moreover, SP-D released from NPs showed biological activity for several days and in vivo release experiment of SP-D loaded NPs revealed that SP-D was released from NPs in mouse lungs with different NPs delivery doses.Nanosized gel particles, so-called nanogels, have attracted substantial interest in different application fields, thanks to their controllable and three-dimensional physical structure, good mechanical properties and potential biocompatibility. Literature reports many technologies for their preparation and design, however a recurrent limitation remains in their broad size distributions as well as in the poor size control. Therefore, the monodisperse and size-controlled nanogels preparation by simple process -like emulsification- is a real challenge still in abeyance to date. In this study we propose an original low energy emulsification approach for the production of monodisperse nanogels, for which the size can be finely controlled in the range 30 to 200 nm. The principle lies in the fabrication of a direct nano-emulsion containing both oil (medium chain triglycerides) and a bi-functional acrylate monomer. The nanogels are thus formed in situ upon UV irradiation of the droplet suspension. Advantage of such modification of the oil nano-carriers are the potential modulation of the release of encapsulated drugs, as a function of the density and/or properties of the polymer chain network entrapped in the oil nano-droplets. This hypothesis was confirmed using a model of hydrophobic drug -ketoprofen- entrapped into the nanogels particles, along with the study of the release profile, carried out in function of the nature of the monomers, density of polymer chains, and different formulation parameters.Oral drug delivery systems for time-controlled release, intended for chronotherapy or colon targeting, are often in the form of coated dosage forms provided with swellable/soluble hydrophilic polymer coatings. These are responsible for programmable lag phases prior to release, due to their progressive hydration in the biological fluids. When based on high-viscosity polymers and/or manufactured by press-coating, the performance of functional hydroxypropyl methylcellulose (HPMC) layers was not fully satisfactory. Particularly, it encompassed an initial phase of slow release because of outward diffusion of the drug through a persistent gel barrier surrounding the core. To promote erosion of such a barrier, the use of a cellulolytic product (Sternzym® C13030) was here explored. For this purpose, the mass loss behavior of tableted matrices based on various HPMC grades, containing increasing percentages of Sternzym® C13030, was preliminarily studied, highlighting a clear and concentration-dependent effect of the enzyme especially with high-viscosity polymers. Subsequently, Sternzym® C13030-containing systems, wherein the cellulolytic product was either incorporated into a high-viscosity HPMC coating or formed a separate underlying layer, were manufactured. Evaluated for release, such systems gave rise to more reproducible profiles, with shortened lag phases and reduced diffusional release, as compared to the reference formulation devoid of enzyme.In this work, the manufacturing process of a complex liposomal amphotericin B (AmB) product was optimized using quality by design (QbD) approach. A comprehensive QbD-based process understanding and design space (DS) to the critical process parameters (CPPs) is essential to the drug development and consistent quality control. The process was based on the acid-aided formation of drug-lipid complexes in a methanol-chloroform mixture (step I) followed by spray drying (step II), hydration and liposome formation by microfluidization (step III), and lyophilization (step IV). Firstly, the risk assessment was conducted to identify the critical process parameters among the four key steps. Nine CPPs and five CQAs (API Monomer identity (absorbance main peak at 321 nm), API Aggregation identity (absorbance peak ratio, OD 415 nm/321 nm), particle size, in-vitro toxicity, and the cake quality) were determined based on their severity and occurrences with their contribution to the quality target product profile (QTPP). Based on the risk assessment results, the final screening design of experiments (DoE) was developed using fractional factorial design. Secondly, the empirical equation was developed for each CQA based on experimental data. The impact of CPPs on the CQAs was analyzed using the coefficient plot and contour plot. In addition to the effect of individual formulation parameters and process parameters, the effects of the four key separate steps were also evaluated and compared. In general, the curing temperature during microfluidization has been identified as the most significant CPP. Finally, design space exploration was carried out to demonstrate how the critical process parameters can be varied to consistently produce a drug product with desired characteristics. The design space size increased at the higher value of the curing temperature, the API to phospholipid ratio (APIPL), and the lower value of the DSPG to phospholipid ratio (PGPL) and aspirator rate.RNA interference induced by small interfering RNA (siRNA) is a promising strategy for the treatment of various intractable diseases including cancer. Lipid nanoparticles (LNP) composed of ionizable lipids and siRNA are known as a leading siRNA delivery system. However, LNPs composed of conventional ionizable lipids will be aggregated in the physiological environment because of loss of ionization. Therefore, the inclusion of hydrophilic polymer-conjugated lipids such as polyethylene glycol (PEG)-conjugated lipid is required to improve the LNP stability. Herein, we synthesized a novel charge-reversible lipid derivative, dioleoylglycerophosphate-diethylenediamine conjugate (DOP-DEDA). The surface of LNP composed of DOP-DEDA (DOP-DEDA LNP) was constantly ionized and positively charged at pH 6.0, almost neutral at pH 7.4, and negatively charged at pH 8.0. selleck products Importantly, DOP-DEDA LNP were stable in the physiological milieu without PEG-conjugated lipid. DOP-DEDA LNP disrupted the red blood cells only under the low-pH condition in a hemolysis assay, suggesting that the interaction between DOP-DEDA LNP and biological membranes is pH-dependent.