Controlled release of bioactive doxorubicin from microspheres embedded within gelatin scaffolds

Abstract

We have encapsulated the chemotherapeutic agent doxorubicin into biodegradable polymer microspheres, and incorporated these microspheres into gelatin scaffolds, resulting in a controlled delivery system. Doxorubicin was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) using a double emulsion/solvent extraction method. Characterization of the microspheres including diameter, surface morphology, and in vitro drug release was determined. The release of doxorubicin up to 30 days in phosphate buffered solution was assessed by measuring the absorbance of the releasate solution. Gelatin scaffolds were crosslinked using glutaraldehyde and microspheres were added to gelatin during gelation. The murine mammary mouse tumor cell line, 4T1, was treated with various doses of doxorubicin. A propidium iodide assay was utilized to visualize dead cells. Using a Transwell basket assay, PLGA microspheres and gelatin constructs were suspended above 4T1 cells for 48 h. Viable cells were determined using the CyQUANT cell proliferation assay. Results indicate that the release was controlled by the incorporation of PLGA microspheres into gelatin constructs. A significant difference was seen in the cumulative release over days 5-16 (p < 0.05). The bioactivity of doxorubicin released from the microspheres and scaffolds was maintained as proven by significant reduction in viable cells after treatment with PLGA microspheres as well as with the gelatin constructs (p < 0.001). The drug-polymer conjugate can be used as a controlled drug delivery system in a biocompatible scaffold that could potentially promote preservation of soft tissue contour.

Dexamethasone Release from Within Engineered Cartilage as a Chondroprotective Strategy Against Interleukin-1α

“…44 Recent work has exploited poly(lactic-co-glycolic acid) (PLGA) systems for the delivery of anti-inflammatory drugs. [45][46][47][48][49][50][51][52][53] Higaki et al demonstrated that the continuous administration of betamethasone sodium phosphate through PLGA nanoparticles provided increased inhibition of inflammation in an experimental model of OA when compared with the same dosage of betamethasone sodium phosphate delivered three times through IA injection. 54 Dang et al demonstrated that dex releasing PLGA microparticles are capable of suppressing the host response to implanted polymer materials in a mouse model.…”

Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release

“…8 To prevent cancer recurrence, chemotherapeutic drugs have been incorporated into the scaffold. 9,10 There is an increasing interest in fabrication of drug-eluting bone tissue engineering scaffolds because these scaffolds provide an approach that conventional medical practice does not offer. [11][12][13] One such drug-eluting scaffold is a ceramic scaffold which is osteoconductive and able to carry drugs.…”

Electrostatic self-assembly of multilayer copolymeric membranes on the surface of porous tantalum implants for sustained release of doxorubicin

“…Researchers are still trying to design a multifunctionalized implant to not only support the skeletal structure but also provide local, controllable release of an anticancer drug in order to prevent cancer recurrence. 14,15 In the current study we intended to functionalize the surface of the porous tantalum implant so as to have a sustained drug delivery capability via electrostatic self-assembly of polyelectrolytes of hyaluronic acid, methylated collagen, and terpolymer of hydroxylethyl methacrylate-methyl methacrylate-methylacrylic acid (HEMA-MMA-MAA). The anticancer drug doxorubicin (DOX) was encapsulated into the multilayer copolymer membranes on the porous tantalum implants.…”