DNA scaffold nanoparticles coated with HPMC/EC for oral delivery

• Published in: International journal of pharmaceutics 2019-05, Vol.562, p.321-332
• Main Authors: Baig, Mirza Muhammad Faran Ashraf, Naveed, Muhammad, Abbas, Muhammad, Chunxia, Wen, Ullah, Sana, Hasnat, Muhammad, Shad, Asam, Sohail, Muhammad, Khan, Ghulam Jilany, Ansari, Muhammad Tayyab
• Format: Article
• Language: English
• Subjects: Db-Db/mice; Diabetes/T2; DPP-4; GLP-1 & GIP; HPMC/EC-DNA-VD nanoparticles; Vildagliptin (VD)
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2019.03.054

[Display omitted] •The control of the glycemic level among diabetes/T2 patients is very important for their long-term survival and avoiding further complexities including micro/macrovascular diseases as well as diabetic neuropathy.•The recent development in the management/treatment of diabetes aims to improve the pancreatic alpha and beta cells functioning. Vildagliptin (VD) is a drug that has addressed these issues successfully with the desired safety portfolio.•We used DNA-nanocubes for initial nano-encapsulation of VD followed by HPMC/coating via solvent evaporation technique to attain polymer protected nano-sized spheres with better size uniformity and control at nanoscale-level.•For characterization of the nanoparticles, we employed ATR/FTIR, PAGE analysis (native), XRD, AFM as well as DSC techniques.•Animal experiments results revealed the improvement of incretin level in the serums due to potent DPP-4 inhibition compared to the free-VD/solution with better maintenance of glycemic levels after feeding. The control of the glycemic level among diabetes/T2 patients is very important for their long term survival and avoiding further complexities including micro/macrovascular diseases as well as diabetic neuropathy. Vildagliptin (VD) is a drug that has addressed these issues successfully with the desired safety portfolio. We used DNA-nanocubes for initial nano-encapsulation of VD followed by HPMC/EC coating. The results revealed the stable, smooth, spherical and nano-sized nanoparticles with improved size uniformity (from 100 to 400 nm in diameter) and encapsulation-efficiency (E.E.%) than previously reported (500–2000 nm) with the chemical compatibility evident in ATR/FTIR and DSC results. Animal experiments results revealed the improvement of incretin level in the serums due to potent DPP-4 inhibition compared to the free-VD/solution with better maintenance of glycemic levels after feeding. The safety of these HPMC/EC-DNA-VD nanoparticles was assessed through the histological-examination after completion of the treatment turn. The solvent evaporation technique provided the better coating of HPMC around DNA-core with gastro-resistant and effervescent property due to presence of NaHCO3 (0.01%) in the formulations that caused delayed delivery of VD as well as nanoparticles to the intestine, increasing the availability time of the drug and nanospheres at the target sites (intestine and blood) where DPP-4 enzyme is most abundant (to degrade the GLP-1 and GIP