Purpose Estradiol (E2)-loaded poly(L-lactide-co-glycolide-trimethylenecarbonate) (P(L-LA:GA:TMC)) rods with shape-memory were developed for the treatment of neurodegenerative diseases. Usefulness of the extrusion method in the obtaining process was also considered. The influence of structural and surface properties during hydrolytic degradation was developed. The possible therapeutic aspect of rods with E2 was determined. Methods The extruded rods were incubated in a PBS solution (pH 7.4, 37°C, 240 rpm). The amount of released E2 in vitro conditions was estimated by UV-VIS method. The following methods in the degradation of rods were applied: NMR, DSC, FTIR, GPC, SEM, and optical microscopy. Changes in water uptake and weight loss were also determined. In vivo study was performed on rats. Measurements of E2 level were performed before and after ovariectomy of rats using ELISA method. A sample of tissue adjacent to the site of the rod implantation was analysed under an optical microscope. Results A stable and steady degradation process ensured zero-order release of E2. The in vivo study indicated a significant increase in the E2 level in serum after ovariectomy. Moreover, structural and surface features indicated that the extrusion method was appropriate for obtaining E2-loaded rods. Conclusions Shape-memory P(L-LA:GA:TMC) rods with E2 are an adequate proposal for further research in the field of neurological disorders.

Latanoprost (LTP) is a prostaglandin F_2α analog used to lower intraocular pressure in glaucoma treatment administered daily as eye drops. In this study, a universal model based on poly(l-lactide-co-glycolide-co-trimethylene carbonate) with shape memory was proposed for the development of a solid biodegradable formulation with prolonged release administered intraconjunctivally, intravitreally, subconjunctivally, and subcutaneously. Solution casting and electron beam (EB) irradiation were applied to the matrix formulation. The properties of the native matrix and matrices degraded in a PBS buffer (pH 7.4) were monitored by NMR, DSC, GPC, and SEM. Water uptake (WU) and weight loss (WL) were also analyzed. LTP was released over 113 days in a tri-phasic and sigmoidal pattern without a burst effect and with a relatively long second release phase, in which changes were observed in the glass transition temperature, molecular weight (M_n), WU, and WL. EB irradiation decreased the initial M_n, increased WU, and accelerated LTP release with a shortened lag phase. This provides the opportunity to partially eliminate the use of drops at the start of treatment. SEM observations indicated that surface erosion is the prevalent degradation mechanism. The proposed model is an interesting solution during a preliminary study to develop final medicinal products that provide high adherence.

In this work, we aimed to determine the role of the mechanical, structural, and thermal properties of poly(l-lactide-co-glycolide-co-trimethylene carbonate) (P(l-LA:GA:TMC)) with shape memory in the formulation of implantable and biodegradable rods with aripiprazole (ARP). Hot melt extrusion (HME) and electron beam (EB) irradiation were applied in the formulation process of blank rods and rods with ARP. Rod degradation was carried out in a PBS solution. HPLC; NMR; DSC; compression and tensile tests; molecular weight (M_n); water uptake (WU); and weight loss (WL) analyses; and SEM were used in this study. HME and EB irradiation did not influence the structure of ARP. The mechanical tests indicated that the rods may be safely implanted using a pre-filled syringe. During degradation, no unfavorable changes in terpolymer content were observed. A decrease in the glass transition temperature and the M_n, and an increase in the WU and the WL were revealed. The loading of ARP and EB irradiation induced earlier pore formation and more intense WU and WL changes. ARP was released in a tri-phasic model with the lag phase; therefore, the proposed formulation may be administered as a delayed-release system. EB irradiation was found to accelerate ARP release.

Aripiprazole (ARP) is an atypical neuroleptic used in the therapy of mental diseases such as schizophrenia. The lack of optimal adherence to an oral therapy regime creates the basis for designing ARP long-acting injections. This study aimed to use 105 °C hot melt extrusion (HME) as a formulation method for rods based on poly(d,l-lactide-co-glycolide-co-trimethylene carbonate) with a molecular weight (M_n) of 21 kDa (Td,l 21), poly(l-lactide-co-glycolide-co-trimethylene carbonate) with a M_n of 59 kDa (Tl 59), and with a M_n of 77 kDa (Tl 77). The following methods were involved in the research: NMR, DSC, XRD, HSM, FTIR, GPC, SEM, and mechanical tests. HME at 105 °C (i) ensured flow behavior for terpolymers, (ii) did not influence the terpolymers’ composition and (iii) the polymorph changes of ARP, and (iv) resulted in the changes in terpolymers’ M_n. For the rods with ARP based on Td,l 21 (Td,l 21 rod-ARP) and Tl 59 (Tl 59 rod-ARP), plasticization was noted. No drug–terpolymer interactions were revealed. No pores were observed on the surface. Due to its high flexibility and rubber character, Td,l 21 rod-ARP may be proposed for intramuscular administration, whereas Tl 59 rod-ARP, due to its higher strength and moderate stiffness, is proposed for subcutaneous administration.