Comparison of drug release from poly(lactide-co-glycolide) microspheres and novel fibre formulations

Abstract

Intraperitoneal cisplatin delivery has recently been shown to benefit ovarian cancer patients. Cisplatin-containing poly(lactide-co-glycolide) (PLGA) microspheres have been proposed for cisplatin delivery. The drug loading of cisplatin containing microspheres produced elsewhere is 3-10%w. Similar microspheres are reported here with a mean diameter of 38.8 µm, and a drug loading of 11.7%w, but using ethyl acetate as a safer solvent. In addition, novel formulations of cisplatin-containing solid and hollow PLGA 65:35 (lactide:glycolide) fibres were prepared and are reported here for the first time. PLGA hollow fibres were produced by phase inversion with a high drug loading of 27%w. Mechanistic mathematical models were applied to the cisplatin release profiles to allow quantitative comparison of microsphere, solid fibre and hollow fibre formulations. The diffusion coefficient of cisplatin eluting from a typical batch of PLGA microspheres was 4.8 × 10(-13) cm(2) s(-1); this low diffusivity of cisplatin in microspheres was caused by the low porosity of the polymer matrix. The diffusion coefficients of cisplatin eluting from a batch of PLGA solid fibres and hollow fibres were 6.1 × 10(-10) and 3.3 × 10(-10) cm(2) s(-1), respectively. These fibres allowed the controlled release of high doses of cisplatin over four days and may represent an improvement in slow release technology for treatment of ovarian cancer.

PLGA nano‐ and microparticles for the controlled release of florfenicol: Experimental and theoretical study

“…For simulations corresponding to the Release Module, the transport parameters used to fit the model are presented in Table . The estimated value of the drug effective diffusivity was 2 × 10 −14 cm 2 s −1 , which is in agreement with those reported for drugs of similar physicochemical characteristics (molar mass and water solubility) in PLGA microspheres under similar conditions …”

Controlled Release Characteristics of Aqueous PEO‐PPO‐PEO Micelles With Added Malachite Green, Erythrosin, and Cisplatin Determined by UV–Visible Spectroscopy

“…Our diffusion results are higher than Campbell et al () who observed much slower cisplatin diffusivity from PLGA microspheres. Campbell's lower diffusivity of cisplatin was caused by the low molecular mobility of the matrices where cisplatin is encapsulated.…”

“…Our results are compared to the in vitro release of cisplatin from core‐shell poly(lactide‐ co ‐glycolide) (PLGA) nanoparticles (Reardon et al, ), PLGA microspheres, solid fibers, and hollow fibers (Campbell et al, ), and electrostatically cross‐linked chitosan‐alginate nanoparticles (Maan et al, )…”

“…Table presents our results and includes a comparison of cisplatin diffusion coefficient values in a variety of delivery systems. The table includes references for cisplatin released from PLGA nanoparticles (Reardon et al, ), PLGA microspheres, solid fibers, and hollow fibers (Campbell, Delgado‐Charro, Camus, & Perera, ), and chitosan‐alginate nanoparticles (Maan, Bajpai, & Bajpai, ).…”

“…Campbell et al reported some microspheres engulfed other microspheres, with shell‐like pores surrounding some regions of a microsphere causing droplets of oil to disperse in the aqueous phase. The low porosity of these microspheres suggests more sluggish drug permeability as there are few aqueous channels to allow paths for drug escape (Campbell et al, ). Campbell also observed a cumulative drug release over 500 h, while our reported diffusion coefficient numbers are within the first 5 h of release.…”