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The impacts of PLGA/PEG triblock copolymers with variable molecular weights on sustained release of buprenorphine

Author(s):

Hossein Kamali , Elham Khodaverdi, Fatemeh Mohammadpour, Ali Kakavand , Seyedeh Nesa Rezaeian Shiadeh , Fatemeh Oroojalian* and Farzin Hadizadeh*  

Abstract:


Introduction: Current in-situ injectable implants of buprenorphine (BP) such as Sublocade® consist of N-methyl-2-pyrrolidone (NMP)-dissolved PLGA. To control the initial burst release of Sublocade® during the first 24 hours after injection, we used a BP in-situ forming composite (ISFC) to employ different molecular weights of PLGA-PEG-PLGA triblock.

Methods: The triblock was synthesized by ring-opening polymerization (ROP) using PEG molecules with weights of 1500, 3000, and 4000 Da via the melting method. The specifications of the triblock were evaluated by 1H-NMR, FTIR, GPC, and DSC. The sol-gel, gel-precipitate temperatures, in-vitro release, and composites’ morphology, degradation, and toxicity were assessed for determining the features of ISFC 1500, ISFC 3000, and ISFC 4000 formulations. ROP was performed successfully via the melting method. The yields of all polymerization reactions were greater than 83.4 %.

Results: The PEG 1500 triblock showed both sol-gel and gel-precipitate temperatures, but PEG 3000 and 4000 only showed a sol-precipitate temperature. The values of initial burst release of BP from ISFC 1500, ISFC 3000, and ISFC 4000 were 6.52 ± 0.22 %, 12.39 ± 0.61 %, and 15.80 ± 0.98 %, respectively. BP release from the ISFCs was completed over three weeks for ISFC 1500 and 10 days for ISFC 3000 and ISFC 4000. The composites containing PEG 3000 and PEG 4000 were more spongy and porous than PEG 1500. The ISFC 1500 delivered a higher cell viability (95.17 ± 1.15 %) compared with ISFC 3000 (86.37 ± 2.25%) and ISFC 4000 (79.70 ± 3.77%).

Conclusion: These results indicated that ISFC 1500 were biocompatible and delivered suitable early initial burst reactions compared with ISFC 3000 and 4000 and might be a good candidate for preparing sustained-release formulation of BP.

Keywords:

In-situ forming composite, PLGA/PEG triblock, Buprenorphine, Initial burst release, Sustained-release, biodegradable polymers

Affiliation:

Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Nanotechnology Research Institute, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Department of Advanced Sciences and Technologies in Medicine, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad



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