Preparation and in vitro characterization of dexamethasone-loaded poly( d,l -lactic acid) microspheres embedded in poly(ethylene glycol)–poly( ɛ -caprolactone)–poly(ethylene glycol) hydrogel for orthopedic tissue engineering
Restricted accessResearch articleFirst published online August, 2013
Preparation and in vitro characterization of dexamethasone-loaded poly( d,l -lactic acid) microspheres embedded in poly(ethylene glycol)–poly( ɛ -caprolactone)–poly(ethylene glycol) hydrogel for orthopedic tissue engineering
The corium is decreased to about half of its thickness in skin defects and wrinkles due to gravity and environment. In this study, dexamethasone/poly(d,l-lactic acid) (Mn = 160,000) microspheres were incorporated into poly(ethylene glycol)–poly(ɛ-caprolactone)–poly(ethylene glycol) (Mn = 3300) hydrogel to prepare an injectable hydrogel composite. The composite was designed to increase the thickness of the corium. Dexamethasone/poly(d,l-lactic acid) microspheres were prepared by oil-in-water emulsion/solvent evaporation technique. The properties of microspheres were investigated by size distribution measurement, scanning electron microscope and x-ray diffraction. Drug loading, encapsulation efficiency, and drug delivery behavior of microspheres were also studied in detail. Cell adhesion of microspheres was investigated by NIH3T3 cell in vitro. The properties of hydrogel composite were investigated by scanning electron microscope, rheological measurements and methyl thiazolyl tetrazolium assay. Drug release from composite was determined by HPLC-UV analysis. These results suggested that poly(d,l-lactic acid) microspheres encapsulating dexamethasone embedded in poly(ethylene glycol)–poly(ɛ-caprolactone)–poly(ethylene glycol) hydrogel might have prospective application in orthopedic tissue engineering field.
RotundaAMNarinsRS. Poly-L-lactic acid: a new dimension in soft tissue augmentation. Dermatol Ther2006; 19: 151–158.
2.
LemperleGAl SoufiA. Faltenbehandlung durch unterfütterung mit artecoll und resurfacing mit dem CO2-laser. Langenbecks Arch Chir Suppl Kongressbd1996; 113: 1128–1134.
3.
LemperleGGauthier-HazanNLemperleM. PMMA-microspheres (Artecoll) for long-lasting correction of wrinkles: refinements and statistical results. Aesth Plast Surg1998; 22: 356–365.
ClarkFriedrich SchierleLaurie ACasas. Nonsurgical rejuvenation of the aging face with injectable poly-L-lactic acid for restoration of soft tissue volume. Aesthet Surg J2011; 31(1): 95–109.
7.
WaltonMCottonNJ. Long-term in vivo degradation of poly-L-lactide (PLLA) in bone. J Biomater Appl2007; 21(4): 395–411.
8.
WeiJDTsengHChenETH. Characterizations of chondrocyte attachment and proliferation scaffolds of PLLA and PBSA for use in cartilage tissue engineering. J Biomater Appl, Epub ahead of print 27 January 2011. DOI: 10.1177/0885328210390401.
9.
XieDParkJ-GZhaoJ. In situ curable alpha-hydroxyacid based degradable polymer composites for injectable biomedical applications. J Compos Mater2008; 42(14): 1385–1400.
10.
ZhangXWyssUPPichoraD. An investigation of poly(lactic acid) degradation. J Bioact Compat Polym1994; 9(1): 80–100.
NicolauPJ. Long-lasting and permanent fillers: biomaterial influence over host tissue response. Plast Reconstr Surg2007; 119: 2271–2286.
13.
BerklandCKimKPackDW. PLG microsphere size controls drug release rate through several competing factors. Pharm Res2003; 20: 1055–1062.
14.
Amard P, Saint Marc T and Katz P. The effects of polylactic acid (NewFill) as therapy for lipoatrophy of the face [Abstract]. In: Proceedings of the second international workshop on adverse drug reactions and lipodystrophy in HIV, Toronto, Canada, 13–15 September 2000, p.94.
15.
SpenlehauerGVertMBenoitJP. In vitro and in vivo degradation of poly(D,L lactide/glycolide) type microspheres made by solvent evaporation method. Biomaterials1989; 10: 557–563.
16.
WoerleBHankeCWSattlerG. Poly-L lactic acid: a temporary filler for soft tissue augmentation. J Drugs Dermatol2004; 3: 385–389.
17.
ParkTGYooHS. Dexamethasone nano-aggregates composed of PEG-PLA-PEG triblock copolymers for anti-proliferation of smooth muscle cells. Int J Pharm2006; 326: 169–173.
18.
FuSZGuoGGongCY. Injectable biodegradable thermosensitive hydrogel composite for orthopedic tissue engineering. 1. Preparation and characterization of nanohydroxyapatite/poly(ethyleneglycol)-poly(ɛ-caprolactone)-poly(ethylene glycol) hydrogel nanocomposites. J Phys Chem B2009; 113: 16518–16525.
19.
GongCYShiSDongPW. Synthesis and characterization of PEG-PCL-PEG thermosensitive hydrogel. Int J Pharm2009; 365: 89–99.
20.
ZolnikBSLearyPEBurgessDJ. Elevated temperature accelerated release testing of PLGA microspheres. J Controlled Release2006; 112: 293–300.
21.
ZolnikBSRatonJLBurgessDJ. Application of USP apparatus 4 and in situfiber optic analysis to microsphere release testing. Dissolut Technol2005; 12: 11–14.
22.
BhardwajUSuraRKPapadimitrakopoulosF. Controlling acute inflammation with fast releasing dexamethasone–PLG Amicrosphere/PVA hydrogel composites for implantable devices. J Diabetes Sci Technol2007; 1: 8–17.
23.
RassoulDShadiHMLeylaMF. Preparation of biodegradable microspheres and matrix devices containing naltrexone. AAPS Pharm Sci Technol2003; 4(3): Article 34.
24.
ISO 10993-5:1999. Biological evaluation of medical devices. Part 5: Tests for in vitro cytotoxicity.
25.
ChunMKChoCSChoiHK. Mucoadhesive microspheres prepared by interpolymer complexation and solvent diffusion method. Int J Pharm2005; 288: 295–303.
26.
SuZXSunFYShiYN. Effects of formulation parameters on encapsulation efficiency and release behavior of risperidone poly(d,l-lactide-co-glycolide) microsphere. Chem Pharm Bull (Tokyo)2009; 57: 1251–1256.
27.
Gómez-GaeteCTsapisNBesnardM. Encapsulation of dexamethasone into biodegradable polymeric nanoparticle. Int J Pharm2007; 331: 153–159.
28.
CoutoDSHongZKManoJF. Development of bioactive and biodegradable chitosan-based injectable systems containing bioactive glass nanoparticles. Acta Biomater2009; 5: 115–123.
29.
ChoJYHeuzeyMCBeginA. Physical gelation of chitosan in the presence of beta-glycerophosphate: the effect of temperature. Biomacromolecules2005; 6: 3267–3275.
30.
YuJWangXTangX. Formulation and in vitro evaluation of biodegradable microspheres of dexamethasone acetate. Asian J Pharm Sci2007; 2(6): 260–268.
