Designing Biodegradable Wafers Based on Poly(L-lactide-co-glycolide) and Poly(glycolide-co-ε-caprolactone) for the Prolonged and Local Release of Idarubicin for the Therapy of Glioblastoma Multiforme

Abstract

Purpose The blood-brain barrier limits the application of idarubicin in the therapy of glioblastoma multiforme. Biodegradable, intracranial wafers with prolonged release may increase therapy efficiency. Methods Blank wafers, wafers containing 5% w/w and 10% w/w of idarubicin were formulated by solution casting from poly(L-lactide-co-glycolide) and poly(glycolide-co-ε-caprolactone). The following methods were used: NMR, GPC, DSC, FTIR, AFM, UV-VIS, and a viability and proliferation assay for idarubicin action (U87MG cell line). Results Wafers showed a surface with numerous immersions and hills. A lack of interactions between idarubicin and the copolymers was observed. The substance was entrapped in the matrix and released in two phases for all wafers with the appropriate bolus and maintenance dose. The burst effect was observed for all wafers, however, the biggest bolus for poly(L-lactide-co-glycolide) wafers containing 5% w/w of idarubicin was noted. The stable and steady degradation of poly(glycolide-co-ε-caprolactone) wafers containing 5% w/w of idarubicin ensures the most optimal release profile and high inhibition of proliferation. Conclusions Copolymer wafers with idarubicin are an interesting proposition with great potential for the local treatment of glioblastoma multiforme. The release rate and dose may be regulated by the amount and kind of wafers for various effects.

A Comprehensive Investigation of the Structural, Thermal, and Biological Properties of Fully Randomized Biomedical Polyesters Synthesized with a Nontoxic Bismuth(III) Catalyst

“…Thermal properties of all synthesized polymers are in close agreement with the literature data: PLA ( X c = 35% [ 29 ], T g = 55–65 °C, T m = 145–183 °C [ 30 , 31 ]); PCL ( T g = −60 °C, T m = 60 °C [ 32 ]; PLACL/50:50 ( T g = 4 °C, T m = 158 °C [ 33 ]); PCLGA of low Gly content ( T g = −60 °C, T m = 54 °C [ 34 , 35 ]). It is known that molecular weight, monomer composition, and crystalline and rigid amorphous fractions development strictly affect thermal properties of polymers [ 30 , 33 , 36 ].…”

The Role of the Mechanical, Structural, and Thermal Properties of Poly(l-lactide-co-glycolide-co-trimethylene carbonate) in the Development of Rods with Aripiprazole

“…The decrease in M n as the result of extrusion may even be up to 64% [ 24 ]. However, it was pointed out that M n is only one of several variables characterizing drug delivery systems [ 9 , 25 ]. In this study, a decrease in M n as a result of HME from 77.1 kDa to 46.8 kDa for P( l -LA:GA:TMC) rods and to 43.9 kDa for P( l -LA:GA:TMC) rods-ARP ( Table 1 , Table 3 and Table 4 ) was observed.…”

Role of Polymeric Local Drug Delivery in Multimodal Treatment of Malignant Glioma: A Review

“… [ 143 ] Idarubicin PLGA, PGACL Wafer In vitro (U87MG cell line). High inhibition of proliferation [ 144 ] Paclitaxel PLGA, PEG NP Orthotopic GS rats (9L) Delayed tumor growth and enhance drug distribution [ 145 ] Camptothecin EVAc Particles Orthotopic GS rats (9L) Significantly extended survival [ 66 ] Doxorubicine PLA, BEP Patch Orthotopic U87-MG canine Suppressed tumor volume and enhanced survival rate [ 146 ] Multiple Agents Concurrent Different Chemotherapy Agents Therapeutical Agent Type of Polymer Structure of Polymeric Vehicle In vivo/in vitro Model Treatment Outcome Ref. BCNU, Cisplatin, Irinotecan PLGA Nanofiber Orthotopic glioma rats (C6) Prolong survival and reduced the malignancy [ 42 , 43 ] Emozolomide, Etoposide PLGA/PEG MP/ paste Orthotopic GS rats (9L) Significant overall survival benefit [ 44 ] Combined Other Biotherapeutic Agent Therapeutic Agent …”