Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases.Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic d...Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases.Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic distribution,leading to a more effective therapy with reduced required doses and side effects.On the other hand,there are several difficulties in obtaining a formulation that would meet all the criteria related to physicochemical,aerodynamic and biological properties,which is the reason why only very few of the investigated systems can reach the clinical trial phase and proceed to everyday use as a result.Therefore,we focused on powders consisting of polysaccharides,lipids,proteins or natural and synthetic polymers in the form of microparticles that are delivered by inhalation to the lungs as drug carriers.We summarized the most common trends in research today to provide the best dry powders in the right fraction for inhalation that would be able to release the drug before being removed by natural mechanisms.This review article addresses the most common manufacturing methods with novel modifications,pros and cons of different materials,drug loading capacities with release profiles,and biological properties such as cytocompatibility,bactericidal or anticancer properties.展开更多
Bone tissue regeneration in critical-size defects is possible after implantation of a 3D scaffold and can be additionally enhanced once the scaffold is enriched with drugs or other factors supporting bone remodelling ...Bone tissue regeneration in critical-size defects is possible after implantation of a 3D scaffold and can be additionally enhanced once the scaffold is enriched with drugs or other factors supporting bone remodelling and healing.Sodium alendronate(Aln),a widely used anti-osteoporosis drug,exhibits strong inhibitory effect on bone resorption performed by osteoclasts.Thus,we propose a new approach for the treatment of bone defects in craniofacial region combining biocompatible titanium dioxide scaffolds and poly(L-lactide-co-glycolide)microparticles(MPs)loaded with Aln.The MPs were effectively attached to the surface of the scaffolds’pore walls by human recombinant collagen.Drug release from the scaffolds was characterized by initial burst(2466%of the drug released within first 24 h)followed by a sustained release phase(on average 5 mg of Aln released per day from Day 3 to Day 18).In vitro tests evidenced that Aln at concentrations of 5 and 2.5 mg/ml was not cytotoxic for MG-63 osteoblast-like cells(viability between 8166%and 9863%of control),but it prevented RANKL-induced formation of osteoclast-like cells from macrophages derived from peripheral blood mononuclear cells,as shown by reduced fusion capability and decreased tartrateresistant acid phosphatase 5b activity(5665%reduction in comparison to control after 8 days of culture).Results show that it is feasible to design the scaffolds providing required doses of Aln inhibiting osteoclastogenesis,reducing osteoclast activity,but not affecting osteoblast functions,which may be beneficial in the treatment of critical-size bone tissue defects.展开更多
基金supported by the National Science Centre,Poland(project No 2019/35/B/ST5/01103)by the Program‘Excellence Initiative-Research University’for the AGH University of Science and Technology。
文摘Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases.Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic distribution,leading to a more effective therapy with reduced required doses and side effects.On the other hand,there are several difficulties in obtaining a formulation that would meet all the criteria related to physicochemical,aerodynamic and biological properties,which is the reason why only very few of the investigated systems can reach the clinical trial phase and proceed to everyday use as a result.Therefore,we focused on powders consisting of polysaccharides,lipids,proteins or natural and synthetic polymers in the form of microparticles that are delivered by inhalation to the lungs as drug carriers.We summarized the most common trends in research today to provide the best dry powders in the right fraction for inhalation that would be able to release the drug before being removed by natural mechanisms.This review article addresses the most common manufacturing methods with novel modifications,pros and cons of different materials,drug loading capacities with release profiles,and biological properties such as cytocompatibility,bactericidal or anticancer properties.
基金This work was supported by National Science Centre,Poland(2013/09/N/ST8/00309)Norwegian Research Council(228415)BMBF,Germany(GoBone German-Polish bilateral project 01DS16010A)。
文摘Bone tissue regeneration in critical-size defects is possible after implantation of a 3D scaffold and can be additionally enhanced once the scaffold is enriched with drugs or other factors supporting bone remodelling and healing.Sodium alendronate(Aln),a widely used anti-osteoporosis drug,exhibits strong inhibitory effect on bone resorption performed by osteoclasts.Thus,we propose a new approach for the treatment of bone defects in craniofacial region combining biocompatible titanium dioxide scaffolds and poly(L-lactide-co-glycolide)microparticles(MPs)loaded with Aln.The MPs were effectively attached to the surface of the scaffolds’pore walls by human recombinant collagen.Drug release from the scaffolds was characterized by initial burst(2466%of the drug released within first 24 h)followed by a sustained release phase(on average 5 mg of Aln released per day from Day 3 to Day 18).In vitro tests evidenced that Aln at concentrations of 5 and 2.5 mg/ml was not cytotoxic for MG-63 osteoblast-like cells(viability between 8166%and 9863%of control),but it prevented RANKL-induced formation of osteoclast-like cells from macrophages derived from peripheral blood mononuclear cells,as shown by reduced fusion capability and decreased tartrateresistant acid phosphatase 5b activity(5665%reduction in comparison to control after 8 days of culture).Results show that it is feasible to design the scaffolds providing required doses of Aln inhibiting osteoclastogenesis,reducing osteoclast activity,but not affecting osteoblast functions,which may be beneficial in the treatment of critical-size bone tissue defects.
