Diprophylline

Zhao, Hong-Ying, et al. Oncology Letters, 2019, 17(1), 857-862.

Diprophylline (DPL) is recognized as a derivative of methylxanthine (MX). This study aimed to explore the effects of DPL on non-small cell lung cancer (NSCLC) and to clarify the underlying mechanisms involved. It was concluded that DPL may hinder the proliferation and migration of NSCLC cells by targeting the PI3K signaling pathway, making DPL a promising candidate for NSCLC treatment.
· Evaluation Methods
The Cell Counting Kit-8 (CCK-8) assay was utilized to assess the impact of DPL on the proliferation of A549 cells. Transwell assays were conducted to determine DPL's effect on both migration and invasion. Additionally, flow cytometry was employed to measure the percentage of apoptotic cells, while western blot analysis evaluated the expression of apoptosis-related proteins such as Bcl-2, BAX, and active caspase-3. Lastly, the expression levels of proteins involved in the phosphoinositide 3-kinase (PI3K) signaling pathway were also assessed via western blot.
· Results
DPL significantly inhibited the proliferation, migration, and invasion of A549 cells. Furthermore, DPL treatment notably induced apoptosis in these cells. Following DPL treatment, the levels of proteins associated with the PI3K signaling pathway in A549 cells were significantly reduced.

Tamani, Fahima, et al. International journal of pharmaceutics, 2019, 572, 118819.

The aim of this study was to better understand the 3 drug release phases observed from poly(Lactic-Co-Glycolic Acid) (PLGA) microparticles containing diprophylline particles: During the burst release, drug crystals directly contacting the surface dissolve rapidly. In the second release phase, tiny drug crystals located near the swelling region (usually) may be released. In the third release phase, the entire microparticle undergoes significant swelling. This results in a large amount of water present throughout the system, becoming "gel-like".
Preparation of Diprophylline-Containing Microparticles
· PLGA microparticles that contained diprophylline were created through a solid-in-oil-in-water (S/O/W) solvent extraction and evaporation process. The organic phase was emulsified into 2.5 L of a 0.25% w/w polyvinyl alcohol aqueous solution and stirred for 30 minutes. After solvent exchange, the PLGA precipitated, capturing the drug. The formed microparticles were hardened by adding 2.5 L of the same external polyvinyl alcohol aqueous solution (0.25%) and further stirred at 700 rpm for 4 h.
· The microparticles were isolated by filtration, washed and freeze-dried to obtain microparticle samples. After fabrication, the tiny drug crystals were fairly uniformly distributed throughout the polymer matrix. "Small" (63 µm), "Medium" (113 µm) and "Large" (296 µm) microparticle batches were prepared with actual drug loadings ranging from 5-7%.