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Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 167
Author(s):  
Chu-Hsun Lu ◽  
Yu-Feng Huang ◽  
I-Ming Chu

Sobrerol, an oral mucolytic agent, in a recent study showed promise for treating multiple sclerosis. A human equivalent dose of 486 mg of sobrerol administered thrice daily (i.e., 1459 mg of daily dose) demonstrated the highest therapeutic efficacy for repurposing use, which also points out the poor compliance of administration. In this study, oral sustained-release pellets of sobrerol were successfully developed with evaluated manufacturing conditions and drug release kinetics. For design of the target drug product, we used a modeling and simulation approach to establish a predictive model of oral pharmacokinetic profile, by exploring the characteristics and correlations corresponding to the pharmacokinetics and pharmacodynamics of sobrerol, such as absorption lag time (0.18 h), time-scaling in vitro–in vivo correlation (tin-vitro = 0.494 tin-vivo − 0.0904), gastrointestinal transit time (8 h), minimum effective concentration (1.61 μg/mL), and duration of action (12.8 h). Results showed that the frequency of administration and the daily dose remarkably reduced by 33.3% (i.e., from thrice to twice daily) and 22.8%, respectively, which indicates that this prototype approach can be adopted for rapidly developing a modified-release dosage form of sobrerol, with improvement of compliance of administration and therapeutic efficacy.


Nanomedicine ◽  
2022 ◽  
Author(s):  
Jihye Baek ◽  
Kwang Il Lee ◽  
Ho Jong Ra ◽  
Martin K Lotz ◽  
Darryl D D'Lima

Aim: To mimic the ultrastructural morphology of the meniscus with nanofiber scaffolds coupled with controlled growth factor delivery to modulate cellular performance for tissue engineering of menisci. Methods: The authors functionalized collagen nanofibers by conjugating heparin to the following growth factors for sustained release: PDGF-BB, TGF-β1 and CTGF. Results: Incorporating growth factors increased human meniscal and synovial cell viability, proliferation and infiltration in vitro, ex vivo and in vivo; upregulated key genes involved in meniscal extracellular matrix synthesis; and enhanced generation of meniscus-like tissue. Conclusion: The authors' results indicate that functionalizing collagen nanofibers can create a cell-favorable micro- and nanoenvironment and can serve as a system for sustained release of bioactive factors.


Author(s):  
PAROMA AREFIN ◽  
MD SHEHAN HABIB ◽  
NAZIM UDDIN AHMED ◽  
MD ABDUR RAHIM ◽  
MD IBRAHIM ◽  
...  

The current treatment approaches for allergic rhinitis are practiced over decades, but the patient quality of life has not yet changed so much. The reasons are research gaps in pathophysiology of the disease, proper management of the disease. Fexofenadine HCl is a second-generation antihistamine drug which has a half-life of about 14.4 h. It is useful in the management of common symptoms like sneezing, itchy throat, and red eyes in individuals suffering from allergic rhinitis. Fexofenadine immediate release or sustained release formulations are available in the market as suspension, tablet and capsule. In this research paper, we have discussed the symptoms associated with allergic rhinitis and treatment approaches. Fexofenadine HCl is being used for the treatment of this disease. But as it has a long half-life, we have discussed the importance of the introduction of sustained-release microsphere formulation of Fexofenadine HCl in the market.


Author(s):  
Kun Liu ◽  
Xin Luo ◽  
Zhao-Yong Lv ◽  
Yu-Jue Zhang ◽  
Zhen Meng ◽  
...  

The effective healing of a bone defect is dependent on the careful coordination of inflammatory and bone-forming cells. In the current work, pro-inflammatory M1 and anti-inflammatory M2 macrophages were co-cultured with primary murine bone mesenchymal stem cells (BMSCs), in vitro, to establish the cross-talk among polarized macrophages and BMSCs, and as well as their effects on osteogenesis. Meanwhile, macrophages influence the osteogenesis of BMSCs through paracrine forms such as exosomes. We focused on whether exosomes of macrophages promote osteogenic differentiation. The results indicated that M1 and M2 polarized macrophage exosomes all can promote osteogenesis of BMSCs. Especially, M1 macrophage-derived exosomes promote osteogenesis of BMSCs through microRNA-21a-5p at the early stage of inflammation. This research helps to develop an understanding of the intricate interactions among BMSCs and macrophages, which can help to improve the process of bone healing as well as additional regenerative processes by local sustained release of exosomes.


Author(s):  
Elena Bellotti ◽  
Gabriella Contarini ◽  
Federica Geraci ◽  
Sebastiano Alfio Torrisi ◽  
Cateno Piazza ◽  
...  

AbstractSchizophrenia is a disorder characterized by cognitive impairment and psychotic symptoms that fluctuate over time and can only be mitigated with the chronic administration of antipsychotics. Here, we propose biodegradable microPlates made of PLGA for the sustained release of risperidone over several weeks. Two microPlate configurations – short: 20 × 20 × 10 μm; tall: 20 × 20 × 20 μm – are engineered and compared to conventional ~ 10 μm PLGA microspheres in terms of risperidone loading and release. Tall microPlates realize the slowest release documenting a 35% risperidone delivery at 100 days with a residual rate of 30 ng/ml. Short microPlates and microspheres present similar release profiles with over 50% of the loaded risperidone delivered within the first 40 days. Then, the therapeutic efficacy of one single intraperitoneal injection of risperidone microPlates is compared to the daily administration of free risperidone in heterozygous knockout mice for dysbindin-1, a clinically relevant mouse model of cognitive and psychiatric liability. In temporal order object recognition tasks, mice treated with risperidone microPlates outperform those receiving free risperidone up to 2, 4, 8, and 12 weeks of observation. This suggests that the sustained release of antipsychotics from one-time microPlate deposition can rescue cognitive impairment in dysbindin mice for up to several weeks. Overall, these results demonstrate that risperidone-loaded microPlates are a promising platform for improving cognitive symptoms associated to schizophrenia. Moreover, the long-term efficacy with one single administration could be of clinical relevance in terms of patient’s compliance and adherence to the treatment regimen. Graphical abstract Single injection of long-acting risperidone-loaded µPL ameliorates the dysbindin-induced deficit in a clinically relevant mouse model of cognitive and psychiatric liability for up to 12 weeks


2022 ◽  
Author(s):  
Xiaoyan Wang ◽  
Xiaona Hu ◽  
Shiqing Li ◽  
Wenhui Shi ◽  
Shujing Li ◽  
...  

The sustained-release antimicrobial nanofibers (PVA-Lut-IC-NF) were prepared by incorporating luteolin-hydroxypropyl-β-cyclodextrin inclusion complex (Lut-IC) into polyvinyl alcohol (PVA) via electrospinning technique. PVA-Lut-IC-NF has shown the excellent water-solubility and thermal stability. The...


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