Nanotechnology - a robust tool for fighting the challenges of drug resistance in non-small cell lung cancer.

Genomic and proteomic mutation analysis is the standard of care for selecting candidates for therapies with tyrosine kinase inhibitors against the human epidermal growth factor receptor (EGFR TKI therapies) and further monitoring cancer treatment efficacy and cancer development. Acquired resistance due to various genetic aberrations is an unavoidable problem during EGFR TKI therapy, leading to the rapid exhaustion of standard molecularly targeted therapeutic options against mutant variants. Attacking multiple molecular targets within one or several signaling pathways by co-delivery of multiple agents is a viable strategy for overcoming and preventing resistance to EGFR TKIs. However, because of the difference in pharmacokinetics among agents, combined therapies may not effectively reach their targets. The obstacles regarding the simultaneous co-delivery of therapeutic agents at the site of action can be overcome using nanomedicine as a platform and nanotools as delivery agents. Precision oncology research to identify targetable biomarkers and optimize tumor homing agents, hand in hand with designing multifunctional and multistage nanocarriers that respond to the inherent heterogeneity of the tumors, may resolve the challenges of inadequate tumor localization, improve intracellular internalization, and bring advantages over conventional nanocarriers.

The potentially harmful excipients in prescribed medications in a Neonatal Intensive Care Unit in Kosovo and available safer alternatives.

BACKGROUND: Medicinal products contain excipients that might be associated with toxicity in neonates. The aim of this study was to investigate the administration of medication containing potentially harmful excipients to neonates hospitalized in Kosovo and to identify the possibility of reducing neonatal exposure to these excipients through product substitution. METHODS: Data on all medication administered to hospitalized neonates from 1st of February to 1st of August 2018 along with patients` demographic data were collected from medical records for each neonate. Excipients were identified from the Summaries of Product Characteristics. Three stage criteria for product substitution were: (1) same active pharmaceutical ingredient (API) and route of administration; (2) 1 plus same dosage form; (3) 1 and 2 plus same strength. RESULTS: In total, 100 excipients were found in 2388 prescriptions comprising 67 medications and 60 API administered to 294 (183 preterm and 111 term) hospitalized neonates. The excipients of interest (EOI) were present in 409 (17.1%) prescriptions and were administered to 131 (71.6%) preterm and 52 (46.8%) term neonates through a relatively small number of products (n=27; 32.8%). In relation to prescription frequency, the most common EOI was polysorbate 80, found in 229 (56%) of EOI-containing prescriptions. Substitution with EOIfree products was possible for 14 (63.6%), 12 (54.5%) and 5 (22.7%) products, according to the first-, second- and third-stage criteria, respectively. CONCLUSIONS: We have provided the first detailed description of neonatal exposure to potentially harmful excipients among neonates admitted to a neonatal intensive care unit in Kosovo. Unnecessary exposure could be reduced by using EOI-free products available in the local medicine market. Collaborative initiative is required to build up the evidence on the use of EOI in neonates and raising awareness among health care professionals on use of products without EOI where possible.

Lactobacillus casei Encapsulated in Soy Protein Isolate and Alginate Microparticles Prepared by Spray Drying.

This article presents a novel formulation for preparation of Lactobacillus casei 01 encapsulated in soy protein isolate and alginate microparticles using spray drying method. A response surface methodology was used to optimise the formulation and the central composite face-centered design was applied to study the effects of critical material attributes and process parameters on viability of the probiotic after microencapsulation and in simulated gastrointestinal conditions. Spherical microparticles were produced in high yield (64%), narrow size distribution (d50=9.7 µm, span=0.47) and favourable mucoadhesive properties, with viability of the probiotic of 11.67, 10.05, 9.47 and 9.20 log CFU/g after microencapsulation, 3 h in simulated gastric and intestinal conditions and four-month cold storage, respectively. Fourier-transform infrared spectroscopy confirmed the probiotic stability after microencapsulation, while differential scanning calorimetry and thermogravimetry pointed to high thermal stability of the soy protein isolate-alginate microparticles with encapsulated probiotic. These favourable properties of the probiotic microparticles make them suitable for incorporation into functional food or pharmaceutical products.

Formulation and characterization of ORMOSIL particles loaded with budesonide for local colonic delivery.

In this study, hybrid silica xerogel particles were developed as carriers of budesonide (BDS) for efficient local treatment of inflammatory bowel diseases (IBD). Organically modified silica particles (ORMOSILs) were prepared by co-condensation of 3-aminopropyltriethoxysilane (APTES) and tetraethyl orthosilicate (TEOS) by an ambient temperature acid catalysed sol-gel process followed by spray-drying. Formulation for preparation of BDS-loaded particles was optimized and their physicochemical parameters and drug release profiles were evaluated in vitro. Optimal formulation had a small particle size (mean diameter of 1.45±0.02µm) with unimodal narrow size distribution and high encapsulation efficiency (98.0 ± 1.85%). Due to the positive surface charge originated from amino group of APTES, ORMOSILs showed excessive mucoadhesiveness in comparison to native TEOS particles. The drug release decreased with increasing pH from 2.0 to 7.4. In order to avoid undesirable erroneous performance in the upper GI tract, particles were additionally coated with Eudragit(®) FS 30D, as a barrier to the drug release at pH range from 2.0 to 7.0. After Eudragit(®) FS 30D coating, the release of BDS in acidic media was sustained, while no significant differences in drug release were observed at pH 7.4. In conclusion, pH-responsive ORMOSILs showed great potential for efficient BDS delivery to the colon region.

Factorial design analysis and optimisation of alginate-Ca-chitosan microspheres.

The purpose of this study was to apply factorial design in order to determine the influence of the formulation factors and their interactions on several responses such as particle size, dissolution behaviour at pH 1.2 and pH 7.4 as well as production yield, during the development of budesonide loaded, chitosan coated Ca-alginate microparticles (MPs) intended for treatment of inflammatory diseases in the gastrointestinal tract. Produced drug-loaded MPs were spherical in shape, had smooth surfaces with low porosity and size range between 5 and 11 µm. Production yield for the formulations from the design varied from 19% to 50%. Optimisation was performed using central composite design setting the targets: particle size at 5.5 µm, maximised yield, suppressed dissolution at pH 1.2 and sustained release at pH 7.4. The optimised batches were identified with a combined desirability value of 0.967.