Localized rosuvastatin via implantable bioerodible sponge and its potential role in augmenting bone healing and regeneration

Abstract

Objective: Statins proved potential bone healing properties. Rosuvastatin is a synthetic, hydrophilic, potent and highly efficacious statin. In the current work, an attempt was investigated to develop, evaluate various bioerodible composite sponges enclosing rosuvastatin and explore their potential in augmenting bone healing and regeneration. Method: Twelve lyophilized sponge formulae were prepared adapting a 4 1 .3 1 full factorial design. Xanthan gum, polycarbophil, Carbopol Õ and sodium alginate were investigated as anionic polymers, each at three chitosan:anionic polymer ratios (1:3, 1:1, 3:1). The formula of choice was implanted in fractured rat femora. Results: Visual and microscopic examination showed flexible homogenous porous structures with considerable bending ability. Polyelectrolyte complex formation was proved by DSC and FT-IR for all chitosan/anionic combinations except with xanthan gum where chitosan probably bound to the drug rather than xanthan gum. Statistical analysis proved that anionic polymer type and chitosan: polymer ratio, as well as, their interactions, exhibited significant effects on the release parameters at p 0.05. The optimum chitosan/anionic polymer complexation ratios were 3:1 for polycarbophil and 1:1 for Carbopol and alginate. The release at these ratios followed Fiction diffusion while other ratios had anomalous diffusion. Imwitor Õ 900K and HPMC K100M were added as release retarardants for further release optimization. The formula of choice was implanted in fractured rat femora. Histopathological examination revealed advanced stages of healing in treated femora compared to control ones. Conclusion: Biodegradable sponges for local rosuvastatin delivery proved significantly enhanced wound healing and regeneration properties to fractured bones.

Histopathologic evaluation of the effects of local simvastatin application and photobiomodulation by light-emitting diode on bone healing of rat calvarial defects

“…Recent studies have investigated the effect of the local application of simvastatin associated with different carriers such as methylcellulose gel [25,37], inorganic bovine bone graft, hydroxiapatite combined with calcium sulphate [38], polylactic acid/polyglycolic acid copolymer [39], calcium sulphate [36,40], lyophilized sponge [41], collagen sponge [42] and gelatin sponge [22,43]. However, there is no consensus about an ideal carrier of the drug for bone defects.…”

Adjuvant Drug-Assisted Bone Healing: Advances and Challenges in Drug Delivery Approaches

“…Variation of chitosan and polymer ratio modulated in vitro release kinetics, whereas rosuvastatin release was completed within a few hours reflecting burst release kinetics. The authors found signs of bone remodeling in histological investigations of rat femoral fractures due to local rosuvastatin delivery [86]. Similarly, Monjo and coworkers incorporated rosuvastatin in a collagen sponge.…”

Tearable and Fillable Composite Sponges Capable of Heat Generation and Drug Release in Response to Alternating Magnetic Field

“…Notably, sponge-like materials are promising implantable carrier materials for DDS because they easily fill defects owing to their tearable and flexible properties [13][14][15][16][17]. To date, various sponge-like materials composed of chitosan, silk, and gelatin have been fabricated by freeze-drying and electrospinning methods [13][14][15][16][17]. However, in many cases, drug release from implantable carriers is difficult to control because they are spontaneously dissolved in the body [17].…”

“…To date, various sponge-like materials composed of chitosan, silk, and gelatin have been fabricated by freeze-drying and electrospinning methods [13][14][15][16][17]. However, in many cases, drug release from implantable carriers is difficult to control because they are spontaneously dissolved in the body [17]. Therefore, researchers have tried to actively control drug release by developing implantable carriers with responsiveness to stimuli such as light [18] and electric fields [19,20].…”

“…To date, porous materials have been developed as implantable carriers for drug delivery systems (DDS) [ 10 , 11 , 12 ]. Notably, sponge-like materials are promising implantable carrier materials for DDS because they easily fill defects owing to their tearable and flexible properties [ 13 , 14 , 15 , 16 , 17 ]. To date, various sponge-like materials composed of chitosan, silk, and gelatin have been fabricated by freeze-drying and electrospinning methods [ 13 , 14 , 15 , 16 , 17 ].…”