-
Journal of Controlled Release :... Nov 2022While all the siRNA drugs on the market target the liver, the lungs offer a variety of currently undruggable targets which could potentially be treated with RNA...
While all the siRNA drugs on the market target the liver, the lungs offer a variety of currently undruggable targets which could potentially be treated with RNA therapeutics. Hence, local, pulmonary delivery of RNA nanoparticles could finally enable delivery beyond the liver. The administration of RNA drugs via dry powder inhalers offers many advantages related to physical, chemical and microbial stability of RNA and nanosuspensions. The present study was therefore designed to test the feasibility of engineering spray dried lipid nanoparticle (LNP) powders. Spray drying was performed using 5% lactose solution (m/V), and the targets were set to obtain nanoparticle sizes after redispersion of spray-dried powders around 150 nm, a residual moisture level below 5%, and RNA loss below 15% at maintained RNA bioactivity. The LNPs consisted of an ionizable cationic lipid which is a sulfur-containing analog of DLin-MC3-DMA, a helper lipid, cholesterol, and PEG-DMG encapsulating siRNA. Prior to the spray drying, the latter process was simulated with a novel dual emission fluorescence spectroscopy method to preselect the highest possible drying temperature and excipient solution maintaining LNP integrity and stability. Through characterization of physicochemical and aerodynamic properties of the spray dried powders, administration criteria for delivery to the lower respiratory tract were fulfilled. Spray dried LNPs penetrated the lung mucus layer and maintained bioactivity for >90% protein downregulation with a confirmed safety profile in a lung adenocarcinoma cell line. Additionally, the spray dried LNPs successfully achieved up to 50% gene silencing of the house keeping gene GAPDH in ex vivo human precision-cut lung slices at without increasing cytokine levels. This study verifies the successful spray drying procedure of LNP-siRNA systems maintaining their integrity and mediating strong gene silencing efficiency on mRNA and protein levels both in vitro and ex vivo. The successful spray drying procedure of LNP-siRNA formulations in 5% lactose solution creates a novel siRNA-based therapy option to target respiratory diseases such as lung cancer, asthma, COPD, cystic fibrosis and viral infections.
Topics: Humans; Powders; RNA, Small Interfering; Lactose; Administration, Inhalation; Spray Drying; Particle Size; Respiratory Aerosols and Droplets; Nanoparticles; Dry Powder Inhalers; Lung; Lipids; Aerosols
PubMed: 36126785
DOI: 10.1016/j.jconrel.2022.09.021 -
Polimery W Medycynie 2022In this review, benefits and drawbacks of the process of spray drying and nano spray drying with regard to the manufacturing of polymeric particles for pharmaceutical... (Review)
Review
In this review, benefits and drawbacks of the process of spray drying and nano spray drying with regard to the manufacturing of polymeric particles for pharmaceutical applications are discussed. Spray drying has been used for many years in the food, chemical and pharmaceutical industries for converting liquids into solids, in order to form products of uniform appearance. The construction of spray dryer enables to atomize the liquid into small droplets, which ensures a large surface area for heat and mass transfer, and significantly shortens the processing. Each droplet dries to an individual solid microparticle of characteristic features that can be tailored by optimizing formulation variables and critical process parameters. Since spray drying technology is easy to scale up and can be used for drying almost any drug in a solution or suspension, there are numerous examples of products in clinical use, in which this process has been successfully applied to improve drug stability, enhance bioavailability or control its release rate. In recent years, nano spray drying technology has been proposed as a method for lab-scale manufacturing of nanoparticles. Such an approach is of particular interest at early stages of drug development, when a small amount of new chemical entities is available. Here, the nebulization technique is used for feed atomization, while laminar gas flow in the drying chamber ensures gentle drying conditions. Moreover, electrostatic collectors have gradually replaced cyclone separators, ensuring high effectiveness in producing solid nanoparticles, even if a small volume of the sample is processed.
Topics: Technology, Pharmaceutical; Drug Industry; Spray Drying; Nanoparticles; Drug Stability; Polymers; Particle Size
PubMed: 35959704
DOI: 10.17219/pim/152230 -
Pharmaceutics Jan 2020Although dry powder inhalers (DPIs) have attracted great interest compared to nebulizers and metered-dose inhalers (MDIs), drug deposition in the deep lung is still... (Review)
Review
Although dry powder inhalers (DPIs) have attracted great interest compared to nebulizers and metered-dose inhalers (MDIs), drug deposition in the deep lung is still insufficient to enhance therapeutic activity. Indeed, it is estimated that only 10%-15% of the drug reaches the deep lung while 20% of the drug is lost in the oropharyngeal sphere and 65% is not released from the carrier. The potentiality of the powders to disperse in the air during the patient's inhalation, the aerosolization, should be optimized. To do so, new strategies, in addition to classical lactose-carrier, have emerged. The lung deposition of carrier-free particles, mainly produced by spray drying, is higher due to non-interparticulate forces between the carrier and drug, as well as better powder uniformity and aerosolization. Moreover, the association of two or three active ingredients within the same powder seems easier. This review is focused on a new type of carrier-free particles which are characterized by a sugar-based core encompassed by a corrugated shell layer produced by spray drying. All excipients used to produce such particles are dissected and their physico-chemical properties (Péclet number, glass transition temperature) are put in relation with the lung deposition ability of powders. The importance of spray-drying parameters on powders' properties and behaviors is also evaluated. Special attention is given to the relation between the morphology (characterized by a corrugated surface) and lung deposition performance. The understanding of the closed relation between particle material composition and spray-drying process parameters, impacting the final powder properties, could help in the development of promising DPI systems suitable for local or systemic drug delivery.
PubMed: 31936628
DOI: 10.3390/pharmaceutics12010055 -
Polymers Oct 2023Enzyme-treated cellulose nanofibrils (CNFs) were produced via a lab-scale mass colloider using bleached kraft pulp (BKP) to evaluate their processability and power...
Enzyme-treated cellulose nanofibrils (CNFs) were produced via a lab-scale mass colloider using bleached kraft pulp (BKP) to evaluate their processability and power requirements during refining and spray-drying operations. To evaluate the energy efficiency in the CNF refining process, the net energy consumption, degree of polymerization (DP), and viscosity were determined. Less energy was consumed to attain a given fines level by using the endoglucanase enzymes. The DP and viscosity were also decreased using the enzymes. The morphological properties of the enzyme-pretreated spray-dried CNF powders (SDCNFs) were measured. Subsequently, the enzyme-pretreated SDCNFs were added to a PP matrix with MAPP as a coupling agent. The mixture was then compounded through a co-rotating twin-screw extruder to determine whether the enzyme treatment of the CNFs affects the mechanical properties of the composites. Compared to earlier studies on enhancing PMCs with SDCNF powders, this research investigates the use of enzyme-pretreated SDCNF powders. It was confirmed that the strength properties of PP increased by adding SDCNFs, and the strength properties were maintained after adding enzyme-pretreated SDCNFs.
PubMed: 37896330
DOI: 10.3390/polym15204086 -
Foods (Basel, Switzerland) May 2023Bioactive peptides derived from enzymatic hydrolysis are gaining attention for the production of supplements, pharmaceutical compounds, and functional foods. However,... (Review)
Review
Bioactive peptides derived from enzymatic hydrolysis are gaining attention for the production of supplements, pharmaceutical compounds, and functional foods. However, their inclusion in oral delivery systems is constrained by their high susceptibility to degradation during human gastrointestinal digestion. Encapsulating techniques can be used to stabilize functional ingredients, helping to maintain their activity after processing, storage, and digestion, thus improving their bioaccessibility. Monoaxial spray-drying and electrospraying are common and economical techniques used for the encapsulation of nutrients and bioactive compounds in both the pharmaceutical and food industries. Although less studied, the coaxial configuration of both techniques could potentially improve the stabilization of protein-based bioactives via the formation of shell-core structures. This article reviews the application of these techniques, both monoaxial and coaxial configurations, for the encapsulation of bioactive peptides and protein hydrolysates, focusing on the factors affecting the properties of the encapsulates, such as the formulation of the feed solution, selection of carrier and solvent, as well as the processing conditions used. Furthermore, this review covers the release, retention of bioactivity, and stability of peptide-loaded encapsulates after processing and digestion.
PubMed: 37238822
DOI: 10.3390/foods12102005 -
Molecules (Basel, Switzerland) Aug 2020The application of the spray drying technique in the food industry for the production of a broad range of ingredients has become highly desirable compared to other... (Review)
Review
The application of the spray drying technique in the food industry for the production of a broad range of ingredients has become highly desirable compared to other drying techniques. Recently, the spray drying technique has been applied extensively for the production of functional foods, pharmaceuticals and nutraceuticals. Encapsulation using spray drying is highly preferred due to economic advantages compared to other encapsulation methods. Encapsulation of oils using the spray drying technique is carried out in order to enhance the handling properties of the products and to improve oxidation stability by protecting the bioactive compounds. Encapsulation of oils involves several parameters-including inlet and outlet temperatures, total solids, and the type of wall materials-that significantly affect the quality of final product. Therefore, this review highlights the application and optimization of the spray drying process for the encapsulation of oils used as food ingredients.
Topics: Desiccation; Food Industry; Functional Food; Plant Oils
PubMed: 32858785
DOI: 10.3390/molecules25173873 -
Materials (Basel, Switzerland) Dec 2022In pharmaceutical applications, the porous particles of organic compounds can improve the efficiency of drug delivery, for example into the pulmonary system. We report...
In pharmaceutical applications, the porous particles of organic compounds can improve the efficiency of drug delivery, for example into the pulmonary system. We report on the successful preparation of macroporous spherical granules of mannitol using a spray-drying process using polystyrene (PS) beads of ~340 nm diameter as a sacrificial templating agent. An FDA-approved solvent (ethyl acetate) was used to dissolve the PS beads. A combination of infrared spectroscopy and thermogravimetry analysis proved the efficiency of the etching process, provided that enough PS beads were exposed at the granule surface and formed an interconnected network. Using a lab-scale spray dryer and a constant concentration of PS beads, we observed similar granule sizes (~1-3 microns) and different porosity distributions for the mannitol/PS mass ratio ranging from 10:1 to 1:2. When transferred to a pilot-scale spray dryer, the 1:1 mannitol/PS composition resulted in different distributions of granule size and porosity depending on the atomization configuration (two-fluid or rotary nozzle). In all cases, the presence of PS beads in the spray-drying feedstock was found to favor the formation of the α mannitol polymorph and to lead to a small decrease in the mannitol decomposition temperature when heating in an inert atmosphere.
PubMed: 36614363
DOI: 10.3390/ma16010025 -
Materials (Basel, Switzerland) Jul 2022Spray drying is a widely used method of converting liquid material (aqueous or organic solutions, emulsions and suspensions) into a dry powder. Good flowability, narrow... (Review)
Review
Spray drying is a widely used method of converting liquid material (aqueous or organic solutions, emulsions and suspensions) into a dry powder. Good flowability, narrow size distribution, and controllable morphology are inherent in powders produced by spray drying. This review considers the granulation factors that influence the final properties of the silicon nitride dried powders. The first group includes the types of atomizers, manifolds, and drying chamber configurations. The process parameters fall into the second group and include the following: inlet temperature, atomizing air flow, feed flow rate, drying gas flow rate, outlet temperature, and drying time. Finally, the last group, feedstock parameters, includes many factors such as feed surface tension, feed viscosity, solvent type, solid particle concentration, and additives. Given the large number of factors affecting morphology, particle size and moisture, optimizing the spray drying process is usually achieved by the "trial and error" approach. Nevertheless, some factors such as the effect of a solvent, dispersant, binder, and sintering additives considered in the literature that affect the SiN granulation process were reviewed in the work. By summarizing the data available on silicon nitride powder production, the authors attempt to tackle the problem of its emerging demand in science and industry.
PubMed: 35888466
DOI: 10.3390/ma15144999 -
Pharmaceutics Jul 2020Spray drying and electrospraying are well-established drying processes that already have proven their value in the pharmaceutical field. However, there is currently... (Review)
Review
Spray drying and electrospraying are well-established drying processes that already have proven their value in the pharmaceutical field. However, there is currently still a lack of knowledge on the fundamentals of the particle formation process, thereby hampering fast and cost-effective particle engineering. To get a better understanding of how functional particles are formed with respect to process and formulation parameters, it is indispensable to offer a comprehensive overview of critical aspects of the droplet drying and particle formation process. This review therefore closely relates single droplet drying to pharmaceutical applications. Although excellent reviews exist of the different aspects, there is, to the best of our knowledge, no single review that describes all steps that one should consider when trying to engineer a certain type of particle morphology. The findings presented in this article have strengthened the predictive value of single droplet drying for pharmaceutical drying applications like spray drying and electrospraying. Continuous follow-up of the particle formation process in single droplet drying experiments hence allows optimization of manufacturing processes and particle engineering approaches and acceleration of process development.
PubMed: 32635464
DOI: 10.3390/pharmaceutics12070625 -
Foods (Basel, Switzerland) Jul 2022This study investigated the effects of atmospheric spray drying (ASD), low-pressure spray drying (LPSD) and freeze drying (FD) on the properties of serum protein powder,...
This study investigated the effects of atmospheric spray drying (ASD), low-pressure spray drying (LPSD) and freeze drying (FD) on the properties of serum protein powder, including the basic characteristics of the powder, bioactive proteins and changes in protein profile, using a proteomics approach. The total solid and water activity of the powder obtained by FD was significantly higher than that obtained by ASD and LPSD. There was no significant difference in the content of fat, lactose or solubility between the three kinds of powders. The concentration and activity of the proteins/enzymes in the serum protein powder made from LPSD were not altered after drying, similar to FD, although both parameters decreased after ASD. The microstructure of the powder observed by scanning electron microscopy indicated that the powder manufactured by ASD and LPSD was spherical in structure, while that manufactured by FD was flake-like. In total, there were 245 proteins identified in the serum protein concentrate and powder from the three drying methods. These findings indicate that LPSD is an effective and cost-saving method for producing serum whey protein powder.
PubMed: 35885239
DOI: 10.3390/foods11141996