Bioresorbable microspheres as devices for the controlled release of paclitaxel

The release of the anti-cancer drug paclitaxel (PTX) from microspheres of both a bioresorbable poly(ε-caprolactoneoxyethylene- ε-caprolactone) tri-block copolymer and of polyurethanes containing either copolymers with the same composition and different molecular weights or poly(ε-caprolactone) diol as soft segments was studied. The microspheres, both loaded and not with PTX, were prepared by emulsion-evaporation technique, then characterized by SEM and DSC. The quantities of PTX released were measured by HPLC. The results showed slow and very regular releases, which fit very well the Peppas equation, Mt/M? = k · tn, where Mt is the amount of solute released at the time t, M? is the amount of drug released at the plateau condition, k represents the Peppas kinetic constant and n the diffusion order. Most n values are consistent with non-Fickian release mechanisms, with the exceptions of two less hydrophilic polyurethanes

New acrylate terpolymer-based nanoparticles for the release of nucleic acid: a preliminary study

Purpose: Nano-drug delivery systems based on polymeric biomaterials have received considerable interest as drug delivery vehicles. In this work, radical polymerization was carried out in order to obtain nanoparticles based on a new acrylate terpolymer (PBMA-(PEG)MEMA-PDMAEMA). Methods: Nanoparticles were developed in the form both of nanospheres and nanocapsules, an innovative kind of hollow nanoparticles with a great potential because of their low effective density and high specific surface area. The ability of the nanoparticles to load and then release a nucleic acid (DNA) to be used in cancer treatment was also investigated. Results: Scanning electron microscopy analysis showed a spherical shape, nanometric dimensions, and a homogeneous distribution of the nanoparticles, also confirmed by dynamic light scattering measurements. Fourier transform infrared spectroscopy chemical imaging analysis carried out on the nanocapsules before and after removal of the core demonstrated the presence of the cavity. High-performance liquid chromatography analysis confirmed good encapsulation efficiency of DNA both for nanospheres and nanocapsules. Drug release tests showed controlled release kinetics for both the systems with a high release of DNA in the first hours. In vitro MTT assay showed that the particles do not have cytotoxic effects on the cells. Conclusions: The preliminary investigation showed that the terpolymer-based nanoparticles developed in this study could be good candidates to be used as innovative and versatile gene delivery systems

Engineered Matrices Based on Gellan Gum and Biocompatible Synthetic Polymers for the Release of Molecules with Antioxidant Activity

Over the past few decades, microbial polysaccharides hydrogels have been used in the field of tissue regeneration due to their ability to mimic the physical-chemical and mechanical characteristics of the extracellular matrix. Gellan gum, an anionic heteropolysaccharide that can form hydrogel in presence of di or trivalent cations, has interesting properties in terms of biodegradability, biocompatibility and the ability to integrate with surrounding tissues. However, it also has some limitations such as the lack of specific sites within the polysaccharide chains for cell recognition and adhesion, high hygroscopicity and limited mechanical properties. Gellan gum has also been proposed for application in the field of controlled release of bioactive molecules; the bio-inert nature of gellan gum makes it suitable for the encapsulation of biomolecules, drugs, enzymes and nutraceutical formulations. Furthermore, the anionic nature of this polysaccharide makes it suitable as a pH sensitive drug delivery system. This work deals with the production and characterization of hydrogels based on gellan gum and polyvinyl alcohol (PVA) or polyvinylpyrrolidone (PVP) for the creation of matrices, containing curcumin as an antioxidant agent, having a micro-engineered surface obtained using micro-molded silicone molds. The properties of gellan hydrogels mixed with PVA or PVP containing curcumin, before and after crosslinking with Ca2+ ions, were investigated. The highest curcumin solubility was observed in PVP solution (0.0156 mg/mL) as compared to PVA solution (0.0074 mg/mL). The contribution of gellan hydrogels mixed with PVA or PVP to the antioxidant capacity of curcumin, expressed as % inhibition, was 22% and 25%, respectively

Chitosan-Based Macromolecular Biomaterials for the Regeneration of Chondroskeletal and Nerve Tissue

The use of materials, containing the biocompatible and bioresorbable biopolymer poly()-2-amino-2-deoxy--D-glucan, containing some N-acetyl-glucosamine units (chitosan, CHI) and/or its derivatives, to fabricate devices for the regeneration of bone, cartilage and nerve tissue, was reviewed. The CHI-containing devices, to be used for bone and cartilage regeneration and healing, were tested mainly for in vitro cell adhesion and proliferation and for insertion into animals; only the use of CHI in dental surgery has reached the clinical application. Regarding the nerve tissue, only a surgical repair of a 35 mm-long nerve defect in the median nerve of the right arm at elbow level with an artificial nerve graft, comprising an outer microporous conduit of CHI and internal oriented filaments of poly(glycolic acid), was reported. As a consequence, although many positive results have been obtained, much work must still be made, especially for the passage from the experimentation of the CHI-based devices, in vitro and in animals, to their clinical application

A Straightforward Method to Produce Multi-Nanodrug Delivery Systems for Transdermal/Tympanic Patches Using Electrospinning and Electrospray

The delivery of drugs through the skin barrier at a predetermined rate is the aim of transdermal drug delivery systems (TDDSs). However, so far, TDDS has not fully attained its potential as an alternative to hypodermic injections and oral delivery. In this study, we presented a proof of concept of a dual drug-loaded patch made of nanoparticles (NPs) and ultrafine fibers fabricated by using one equipment, i.e., the electrospinning apparatus. Such NP/fiber systems can be useful to release drugs locally through the skin and the tympanic membrane. Briefly, dexamethasone (DEX)-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) fiber meshes were decorated with rhodamine (RHO)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs, with RHO representing as a second drug model. By properly tuning the working parameters of electrospinning, DEX-loaded PHBHV fibers (i.e., by electrospinning mode) and RHO-loaded PLGA NPs (i.e., by electrospray mode) were successfully prepared and straightforwardly assembled to form a TDDS patch, which was characterized via Fourier transform infrared spectroscopy and dynamometry. The patch was then tested in vitro using human dermal fibroblasts (HDFs). The incorporation of DEX significantly reduced the fiber mesh stiffness. In vitro tests with showed that HDFs were viable for 8 days in contact with drug-loaded samples, and significant signs of cytotoxicity were not highlighted. Finally, thanks to a beaded structure of the fibers, a controlled release of DEX from the electrospun patch was obtained over 4 weeks, which may accomplish the therapeutic objective of a local, sustained and prolonged anti-inflammatory action of a TDDS, as is requested in chronic inflammatory conditions, and other pathological conditions, such as in sudden sensorineural hearing loss treatment

Electrospun Poly(3-Hydroxybutyrate-Co-3-Hydroxyvalerate)/Olive Leaf Extract Fiber Mesh as Prospective Bio-Based Scaffold for Wound Healing

Polyhydroxyalkanoates (PHAs) are a family of biopolyesters synthesized by various microorganisms. Due to their biocompatibility and biodegradation, PHAs have been proposed for biomedical applications, including tissue engineering scaffolds. Olive leaf extract (OLE) can be obtained from agri-food biowaste and is a source of polyphenols with remarkable antioxidant properties. This study aimed at incorporating OLE inside poly(hydroxybutyrate-co-hydroxyvalerate) (PHBHV) fibers via electrospinning to obtain bioactive bio-based blends that are useful in wound healing. PHBHV/OLE electrospun fibers with a size of 1.29 ± 0.34 µm were obtained. Fourier transform infrared chemical analysis showed a uniform surface distribution of hydrophilic -OH groups, confirming the presence of OLE in the electrospun fibers. The main OLE phenols were released from the fibers within 6 days. The biodegradation of the scaffolds in phosphate buffered saline was investigated, demonstrating an adequate stability in the presence of metalloproteinase 9 (MMP-9), an enzyme produced in chronic wounds. The scaffolds were preliminarily tested in vitro with HFFF2 fibroblasts and HaCaT keratinocytes, suggesting adequate cytocompatibility. PHBHV/OLE fiber meshes hold promising features for wound healing, including the treatment of ulcers, due to the long period of durability in an inflamed tissue environment and adequate cytocompatibility