Development of an injectable PHBV microparticles-GG hydrogel hybrid system for regenerative medicine

Abstract

Uncontrollable displacements that greatly affect the concentration of active agents at the target tissues are among a major limitation of the use of microparticulate drug delivery systems (DDS). Under this context a biphasic injectable DDS combining poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) microparticles (MPs) and a gellan gum (GG) injectable hydrogel is herein proposed for the localized delivery and long-term retention of MPs carrying hydrophilic and hydrophobic model active agents. A double emulsion-solvent evaporation method was adopted to develop the PHBV MPs, carrying bovine serum albumin (BSA) or dexamethasone (Dex) as hydrophilic and hydrophobic active agents' models, respectively. Moreover, this method was modified, together with the properties of the hydrogel to tailor the delivery profile of the active agents. Variations of the composition of the organic phase during the process allowed tuning surface topography, particle size distribution and core porosity of the PHBV MPs and, thus, the in vitro release profile of Dex but not of BSA. Besides, after embedding hydrogels of higher GG concentration led to a slower and more sustained release of both active agents, independently of the processing conditions of the microparticulate system.

Advances in drug delivery systems based on synthetic poly(hydroxybutyrate) (co)polymers

“…P(R)-HB [93][94][95][96][97], and bacterial copolymers such as P(3HB-co-4HB) [98][99][100], PHBV [101][102][103] or PHBH and derivatives [104][105][106], have been used for the elaboration of self-assembled systems such as DDSs, tissue engineering scaffolds and implants [107][108][109][110]. Those polymers have been chosen for their biodegradability and biocompatibility.…”

Recent advances of using polyhydroxyalkanoate‐based nanovehicles as therapeutic delivery carriers

“…The predominant antibiotic mechanism is through the controlled dissolution of the drug from the PHA rods. Because of the advantages of the controlled release ability of antibiotics and other apatite formations, these PHA‐based formulations combined with other delivery systems could be applied as alternative drug controlled release systems, especially as bone fillings for bone repair applications …”

Evaluation of Biodegradation in Aqueous Medium of Poly(Hydroxybutyrate-Co-Hydroxyvalerate)/Carbon Nanotubes Films in Respirometric System

“…PHBV has attracted significant academic and commercial interests because of its biodegradability, biocompatibility and also because it has some properties similar to conventional thermoplastics [5,6]. In addition to satisfying the requirements that classify it as a biodegradable polymer, PHBV is biocompatible and very similar to conventional thermoplastics, petroleum-based polymers [7,8,9]. It has an important use in the medical field, such as scaffolds [10] and tissue engineering [11].…”