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1.
Int J Pharm ; 562: 228-240, 2019 May 01.
Article in English | MEDLINE | ID: mdl-30849470

ABSTRACT

The present study evaluates the effect of L-leucine concentration and operating parameters of a laboratory spray dryer on characteristics of trehalose dry powders, with the goal of optimizing production of these powders for inhaled drug delivery. Trehalose/L-leucine mixtures were spray dried from aqueous solution using a laboratory spray dryer. A factorial design of experiment (DoE) was undertaken and process parameters adjusted were: inlet temperature, gas flow rate, feed solution flow rate (pump setting), aspiration setting and L-leucine concentration. Resulting powders were characterised in terms of particle size, yield, residual moisture content, and glass transition temperature. Particle size was mainly influenced by gas flow rate, whereas product yield and residual moisture content were found to be primarily affected by inlet temperature and spray solution feed rate respectively. Interactions between a number of different process parameters were elucidated, as were relationships between different responses. The leucine mass ratio influenced the physical stability of powders against environmental humidity, and a high leucine concentration (30% w/w) protected amorphous trehalose from moisture induced crystallization. High weight ratio of leucine in the formulation, however, negatively impacted the aerosol performance. Thus, in terms of L-leucine inclusion in a formulation designed for pulmonary delivery, a balance needs to be found between physical stability and deposition characteristics.


Subject(s)
Drug Compounding/methods , Leucine/chemistry , Trehalose/chemistry , Administration, Inhalation , Aerosols , Desiccation , Drug Design
2.
Lab Chip ; 14(20): 4007-16, 2014 Oct 21.
Article in English | MEDLINE | ID: mdl-25144915

ABSTRACT

The present paper describes the production of microfluidic chips using an approach based on shrinkable biocompatible polymers (i.e. agarose) for the production of size controlled microfluidic channels. In addition, all steps of chip production were carried out using an inexpensive approach that uses low cost chemicals and equipment. The produced chips were then validated by producing monodisperse polymeric microparticles for drug delivery and hydrogel microfibers for cell embedding.


Subject(s)
Biocompatible Materials/chemical synthesis , Microfluidic Analytical Techniques , Polymers/chemical synthesis , Sepharose/chemical synthesis , Biocompatible Materials/chemistry , Microfluidic Analytical Techniques/economics , Microfluidic Analytical Techniques/instrumentation , Polymers/chemistry , Sepharose/chemistry
3.
Biomed Mater ; 8(3): 035011, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23619339

ABSTRACT

A porous scaffold was developed to support normal tissue regeneration in the presence of residual tumor disease. It was prepared by gelatin crosslinked with dehydroascorbic acid (DHA). A physicochemical characterization of the scaffold was carried out. SEM and mercury porosimetry revealed a high porosity and interconnection of pores in the scaffold. Enzymatic degradation provided 56% weight loss in ten days. The scaffold was also evaluated in vitro for its ability to support the growth of normal cells while hindering tumor cell development. For this purpose, primary human fibroblasts and osteosarcoma tumor cells (MG-63) were seeded on the scaffold. Fibroblasts attached the scaffold and proliferated, while the tumor cells, after an initial attachment and growth, failed to proliferate and progressively underwent cell death. This was attributed to the progressive release of DHA during the scaffold degradation and its cytotoxic activity towards tumor cells.


Subject(s)
Antineoplastic Agents/chemistry , Dehydroascorbic Acid/chemistry , Gelatin/chemistry , Tissue Scaffolds/chemistry , Antineoplastic Agents/administration & dosage , Biocompatible Materials/chemistry , Cell Adhesion , Cell Line, Tumor , Cell Proliferation , Cell Survival , Cells, Cultured , Cross-Linking Reagents , Dehydroascorbic Acid/administration & dosage , Humans , Materials Testing , Microscopy, Electron, Scanning , Neoplasm, Residual/drug therapy , Neoplasm, Residual/pathology , Neoplasm, Residual/surgery , Regeneration , Tissue Engineering
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