In situ Formation of Polymer Microparticles in Bacterial Nanocellulose Using Alternative and Sustainable Solvents to Incorporate Lipophilic Drugs

Abstract

Bacterial nanocellulose has been widely investigated in drug delivery, but the incorporation of lipophilic drugs and controlling release kinetics still remain a challenge. The inclusion of polymer particles to encapsulate drugs could address both problems but is reported sparely. In the present study, a formulation approach based on in situ precipitation of poly(lactic-co-glycolic acid) within bacterial nanocellulose was developed using and comparing the conventional solvent N-methyl-2-pyrrolidone and the alternative solvents poly(ethylene glycol), CyreneTM and ethyl lactate. Using the best-performing solvents N-methyl-2-pyrrolidone and ethyl lactate, their fast diffusion during phase inversion led to the formation of homogenously distributed polymer microparticles with average diameters between 2.0 and 6.6 µm within the cellulose matrix. Despite polymer inclusion, the water absorption value of the material still remained at ~50% of the original value and the material was able to release 32 g/100 cm2 of the bound water. Mechanical characteristics were not impaired compared to the native material. The process was suitable for encapsulating the highly lipophilic drugs cannabidiol and 3-O-acetyl-11-keto-β-boswellic acid and enabled their sustained release with zero order kinetics over up to 10 days. Conclusively, controlled drug release for highly lipophilic compounds within bacterial nanocellulose could be achieved using sustainable solvents for preparation.

The Role of Microorganisms in the Isolation of Nanocellulose from Plant Biomass

“…Its high surface area and ability to encapsulate and release therapeutic agents in a controlled manner make it an ideal material for targeted and sustained drug delivery systems. Nanocellulose can also protect sensitive drugs from degradation and improve their stability [73]. Nanocellulose-based films or membranes can be used as a platform for biosensors [74].…”

Exploring Microemulsion Systems for the Incorporation of Glucocorticoids into Bacterial Cellulose: A Novel Approach for Anti-Inflammatory Wound Dressings

“…Previously, strategies to integrate lipophilic compounds focused on drug solubility improvement, the surface modification of BC fibers and the formulation of dispersed systems [ 30 ]. In the case of the latter, recent studies investigating nanoemulsions [ 29 , 31 ], liposomes [ 29 ] or polymeric microparticles [ 32 ], are particularly worthy of mention. However, these approaches have a number of limitations.…”

“…Improving API solubility via salt formation requires certain chemical conditions and high development effort and can significantly influence the physical and chemical properties of the API [ 30 , 33 ]. Surface modification of BC fibers and in situ microparticle formation require the use of organic reagents and solvents, the residues of which must be carefully removed before medical use and may delay the registration process [ 30 , 32 , 34 , 35 ]. Nanoemulsions are thermodynamically unstable, and phase separation due to coalescence, flocculation and Ostwald ripening can be an issue for shelf-life stability, which needs careful formulation design [ 36 ].…”