Amphiphilic Block Copolymer Microspheres Derived from Castor Oil, Poly(ε-carpolactone), and Poly(ethylene glycol): Preparation, Characterization and Application in Naltrexone Drug Delivery

Abstract

In the present study, the newly synthesized castor oil-derived thioether-containing ω-hydroxyacid (TEHA) block copolymers with polycaprolactone (TEHA-b-PCL), with methoxypoly(ethylene glycol) (mPEG), (TEHA-b-mPEG) and with poly(ethylene glycol) (PEG) (TEHA-b-PEG-b-TEHA), were investigated as polymeric carriers for fabrication of naltrexone (NLX)-loaded microspheres by the single emulsion solvent evaporation technique. These microspheres are appropriate for the long-term treatment of opioid/alcohol dependence. Physical properties of the obtained microspheres were characterized in terms of size, morphology, drug loading capacity, and drug release. A scanning electron microscopy study revealed that the desired NLX-loaded uniform microspheres with a mean particle size of 5–10 µm were obtained in all cases. The maximum percentage encapsulation efficiency was found to be about 25.9% for the microspheres obtained from the TEHA-b-PEG-b-TEHA copolymer. Differential scanning calorimetry and X-ray diffractometry analysis confirmed the drug entrapment within microspheres in the amorphous state. In vitro dissolution studies revealed that all NLX-loaded formulations had a similar drug release profile: An initial burst release after 24 h, followed by a sustained and slower drug release for up to 50 days. The analysis of the release kinetic data, which were fitted into the Korsmeyer–Peppas release model, indicated that diffusion is the main release mechanism of NLX from TEHA-b-PCL and TEHA-b-mPEG microspheres, while microspheres obtained from TEHA-b-PEG-b-TEHA exhibited a drug release closer to an erosion process.

Paclitaxel Magnetic Core–Shell Nanoparticles Based on Poly(lactic acid) Semitelechelic Novel Block Copolymers for Combined Hyperthermia and Chemotherapy Treatment of Cancer

“…Since TEHA has only one hydroxyl groups, this can act as initiator for ring opening polymerization of lactide monomer and, according to Figure 1, only block copolymers can be formed since the –COOH end group of TEHA is inactive during ROP of lactide. Similar block copolymers have been reported in literature using methylated poly(ethylene glycol) as initiator for ring opening polymerization reactions [40,41]. The formation of a copolymer is supported also by two additional observations.…”

New Biodegradable Poly(l-lactide)-Block-Poly(propylene adipate) Copolymer Microparticles for Long-Acting Injectables of Naltrexone Drug

“…DSC was further used to confirm these observations. As shown in Figure 13, a sharp endothermic peak is present for NTX at 177.1 °C [11]. Concerning the DSC curves of the prepared microparticles, the peak of Tm of NTX was not observed in any formulation indicating that the drug is present in an amorphous state in the microparticles, as was already suggested by XRD.…”

“…In the FTIR spectrum of NTX, the absorption band at 3000-3100 cm −1 is assigned to the ν(C-H) vibrations of the benzene rings, peaks at 1508 and 1617 cm −1 to the vibration of ν(C=C) bonds. In the ν(C-C) and ν(C-O) regions, NTX exhibits sharp absorption peaks at 1456 cm −1 and 1239 cm −1 respectively, a peak at 1727 cm −1 corresponding to its ν(C=O) vibration modes, and a broad peak in the range 3200-3500 cm −1 due to the existence of OH groups [11]. After the incorporation of NTX, the FTIR spectra of microparticles showed shifts in the region of OH and C=O groups.…”

“…NTX release studies showed an 82% release within 30 days. Nerantzaki et al synthesized a series of castor oil, poly(ε-caprolactone) and poly(ethylene glycol) (PEG) block copolymers [11]. These copolymers were used as polymeric carriers for the fabrication of NTX-loaded microspheres by the single emulsion solvent evaporation technique, resulting in sustained release systems with drug release controlled by diffusion processes.…”

Preparation and characterization of Alendronate depot microspheres based on novel poly(-ε-caprolactone)/Vitamin E TPGS copolymers

“…PCL is a semicrystalline flexible polymer with low melting temperature (∼60 °C), low glass transition temperature (∼−60 °C), appropriate mechanical properties, and good solubility in several solvents (Nanaki et al, 2011). Despite its important advantages, PCL’s high degree of crystallinity and hydrophobicity reduces extensively its compatibility with soft tissues and lowers its in vivo biodegradability (Nerantzaki et al, 2018, Siafaka et al, 2016, Zhang et al, 2015). Hence, in order to overcome these limitations, several attempts have been made to prepare new PCL-based copolymers by adding compounds with higher biodegradation rates (compared to PCL), which eventually will lead to microspheres with tunable biodegradation rate, and hence, tunable API release (Bikiaris et al, 2008, Harada et al, 2008, Nanaki et al, 2011, Yuan et al, 2000, Zorba et al, 2007).…”