Encapsulation of simvastatin in PLGA microspheres loaded into hydrogel loaded BCP porous spongy scaffold as a controlled drug delivery system for bone tissue regeneration

Abstract

The main objective of this study was to fabricate a controlled drug delivery which is simultaneously effective for bone regeneration. We have encapsulated simvastatin, which enhances osteoblastic activity, in the poly (lactic-co-glycolic acid) microspheres. Loading of these microspheres inside the spongy scaffold of biphasic calcium phosphate with the help of Gelatin (Gel) hydrogel controls the delivery of the drug, and ensures a more favorable drug release profile. As a result, some significant benefits have been achieved, such as higher mechanical strength, excellent biocompatibility in in vitro experiments. For determining the characteristics of the composite scaffold, several analysis, such as scanning electron microscope, EDX, X-ray diffraction, FT-IR, and porosity were carried out. The in vitro drug release profile clearly indicates that simvastatin release from the microsphere was more controlled and prolonged after loading in the scaffold. Biocompatibility was certainly higher for the final composite scaffold compared to drug unloaded scaffold, as assessed through MTT assay and Confocal imaging with MC3T3-E1 pre-osteoblast cells. Cell attachment and proliferation were certainly higher in the presence of drug loaded microspheres. Bone remodeling gene and protein expression were observed by real-time polymerase chain reaction and Western blot respectively. Simvastatin loaded scaffold exhibited the best results in every determination which was carried out.

Role of Simvastatin on fracture healing and osteoporosis: a systematic review on in vivo investigations

“…114,115 Alternatively, Simvastatin can be released controllably from microspheres and nanospheres. 11,25,29,40,113,116,117 Simvastatin loaded micro-and nanospheres can be fabricated using various techniques such as single-and double-emulsion technologies. Such spherical structures can be embedded within bone fillers, hydrogels (the most popular model) and scaffolds.…”

“…Such spherical structures can be embedded within bone fillers, hydrogels (the most popular model) and scaffolds. 11,25,29,40,113,116,117 As another strategy, Simvastatin can be conjugated with free molecular sites of the bone scaffolds or chemical compounds (that have high affinity to bone such as bisphosphonates). 42,49,88 This method is currently under development and would be a valuable strategy in the near future.…”

Controlled-release of tetracycline and lovastatin by poly(D,L-lactide-co-glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs

“…24,25 The encapsulation of simvastatin in PLGA microspheres loaded into hydrogel achieved a favorable drug-release profile and enhanced bone remodeling in vitro. 26 Further in vivo experiments revealed that simvastatin loaded PLGA microspheres significantly enhanced bone formation in rabbit calvaria critical size defects, 27 and that lovastatin released from PLGA nanoparticles enhanced bone repair in rats. 28 In randomized clinical trials, locally administered simvastatin significantly improved the clinical outcomes of scaling and root planing for treating mandibular buccal Class II defects, and in patients with chronic periodontitis, even when they were smokers or with type II diabetes.…”

PNIPAAM modified mesoporous hydroxyapatite for sustained osteogenic drug release and promoting cell attachment

“…Therefore, to overcome this problem, polymers such as poly(β-amino ester) (PBAE) [18], polyethylene glycol (PEG) [19], and poly(L-lactic acid) (PLLA) [20] were added to adjust the release profile of the drug. Inorganic porous materials were also used as bone substitutes, such as α-tricalcium phosphate (α-TCP) [21], β-tricalcium phosphate (β-TCP) [22–24], and hydroxyapatite (HA) [18]. SIM was also mixed with these materials to be drug delivery scaffolds.…”