11 research outputs found
Micro-nanostructured polymeric materials with specific functionalities for advanced biomedical applications
The possibility to tune material properties up to nanoscale represents a great opportunity for the scientific community to obtain devices capable to fulfill the always new medical demands. During this Thesis project micro and nano-structured polymeric materials have been used in the field of drug delivery and tissue engineering. Three different research lines have been explored: (i) the use of polymeric fibrous systems as drug and nanoparticles carriers, (ii) design and evaluation of novel shape memory polymers to produce shape memory scaffolds and (iii) development of smart affinity membranes.
Electrospinning were exploited to obtain polymeric fibrous carriers made of different biodegradable and bioresorbable polymers, such us Poly(lactic-acid) and Poly(lactic-co-glycolic). The obtained biodegradable carriers have been exploited to achieve controllable particles release as well as, to obtain composites capable to deliver two drugs simultaneously with controllable and predictable kinetics.
The possibility to obtain electrospun scaffolds capable of interconverting between a temporary and a permanent shape with the application of a thermal stimulus was explored. In this context, two polymers have been designed to behave as shape memory materials in the range of human body temperature.
Finally smart affinity membranes have been studied. This kind of materials are capable to detect specific molecules or biomacromolecules from complex mixtures, finding useful applications in the biomedical field as diagnostic and therapeutic devices. Smart affinity membranes might be used for example to detect specific kind of cells by exploiting the binding interaction between an antibody and cell receptors. During this thesis project poly(L-lactic acid) electrospun scaffolds conjugated with antibodies have been produced and the efficacy of different functionalization methods to generate the –COOH group necessary to perform the antibodies conjugation was investigated
Biodegradable PEG-poly(ω-pentadecalactone- co - p -dioxanone) nanoparticles for enhanced and sustained drug delivery to treat brain tumors
Intracranial delivery of therapeutic agents is limited by penetration beyond the blood-brain barrier (BBB)
and rapid metabolism of the drugs that are delivered. Convection-enhanced delivery (CED) of drugloaded
nanoparticles (NPs) provides for local administration, control of distribution, and sustained
drug release. While some investigators have shown that repeated CED procedures are possible, longer
periods of sustained release could eliminate the need for repeated infusions, which would enhance
safety and translatability of the approach. Here, we demonstrate that nanoparticles formed from
poly(ethylene glycol)-poly(u-pentadecalactone-co-p-dioxanone) block copolymers [PEG-poly(PDL-co-
DO)] are highly efficient nanocarriers that provide long-term release: small nanoparticles (less than
100 nm in diameter) continuously released a radiosensitizer (VE822) over a period of several weeks
in vitro, provided widespread intracranial drug distribution during CED, and yielded significant drug
retention within the brain for over 1 week. One advantage of PEG-poly(PDL-co-DO) nanoparticles is that
hydrophobicity can be tuned by adjusting the ratio of hydrophobic PDL to hydrophilic DO monomers,
thus making it possible to achieve a wide range of drug release rates and drug distribution profiles. When
administered by CED to rats with intracranial RG2 tumors, and combined with a 5-day course of fractionated
radiation therapy, VE822-loaded PEG-poly(PDL-co-DO) NPs significantly prolonged survival
when compared to free VE822. Thus, PEG-poly(PDL-co-DO) NPs represent a new type of versatile
nanocarrier system with potential for sustained intracranial delivery of therapeutic agents to treat brain
tumors
Hydrogelation induced by Fmoc-protected peptidomimetics
Four new low molecular weight hydrogelators (LMWGs) have been prepared in multigram scale and their attitude to form hydrogels has been tested. The gelation trigger is pH variation. The resulting gels have been characterized with several techniques: measurement of the melting points (Tgel), transparency, gelation time, and viscoelastic properties, together with ECD analysis. Among them, Fmoc-l-Tyr-d-Oxd-OH 1 is an excellent gelator that leads to the preparation of strong, transparent, and viscoelastic gels, by pH variation. UV-visible analyses have demonstrated that the gels obtained with the LMWG 1 possess high transparency, with a transmittance up to 25.6% at a wavelength of 600 nm. Results of the amplitude sweep experiments showed that the elastic response component (G′) was approximately an order of magnitude larger than the viscous component, indicating an elastic rather than viscous attitude of the gels, confirmed by the frequency independence of G′ and G″ values, in the range from 0.1 to 100 rad·s-1. The thermal behavior of gel obtained from Fmoc-l-Tyr-d-Oxd-OH 1 was characterized performing an "ad hoc" rheological temperature sweep experiment, that indicated that G′ remained almost constant from 23 °C up to about 65 °C while G″ increased in the same temperature range. At higher temperatures, both G′ and G″ values started to slightly decrease without displaying a crossover point
Two-Way Shape Memory Behavior of Electrospun Non-Woven Mats Prepared from Sol-Gel Crosslinked Poly(ε-Caprolactone)
Non-woven fibrous mats based on semicrystalline networks were prepared starting from poly(ε-caprolactone) and by combining electrospinning process and sol-gel crosslinking reaction. The mats were subjected to proper thermo-mechanical cycles to investigate their two-way shape memory capabilities (i.e. the possibility to change between two distinguished shapes upon heating and cooling), and an improvement of the two-way behaviour was researched through the application of a training cycle. An ex-situ SEM analysis described the microstructural evolution accompanying the two-way shape memory cyclic response
Facile fabrication of shape memory poly(ε-caprolactone) non-woven mat by combining electrospinning and sol–gel reaction
Poly(ε-caprolactone)-based non-woven fibrous mats showing excellent one-way shape memory
properties were obtained through a straightforward approach by combining electrospinning process and
sol–gel reaction. A solution of partially crosslinked α,ω-triethoxysilane-terminated poly(ε-caprolactone)
was used to obtain bead-free fibers through electrospinning. Non-woven mats with different
crosslinking degrees have been prepared and the effect of the different crosslinking extent and of the
microfibrous structure were correlated to the mechanical and shape memory properties of the material.
The evolution of fiber architecture within the non-woven mat following deformation and shape memory
cycles was also investigated
Two-Way Shape Memory Behavior of Electrospun Non-Woven Mats Prepared from Sol-Gel Crosslinked Poly(\u3b5-Caprolactone)
Non-woven fibrous mats based on semicrystalline networks were prepared starting from poly(\u3b5-caprolactone) and by combining electrospinning process and sol-gel crosslinking reaction. The mats were subjected to proper thermo-mechanical cycles to investigate their two-way shape memory capabilities (i.e. the possibility to change between two distinguished shapes upon heating and cooling), and an improvement of the two-way behaviour was researched through the application of a training cycle. An ex-situ SEM analysis described the microstructural evolution accompanying the two-way shape memory cyclic response
Thixotropic Peptide-Based Physical Hydrogels Applied to Three-Dimensional Cell Culture
Pseudopeptides containing
the d-Oxd or the d-pGlu
[Oxd = (4<i>R</i>,5<i>S</i>)-4-methyl-5-carboxyl-oxazolidin-2-one,
pGlu = pyroglutamic acid] moiety and selected amino acids were used
as low-molecular-weight gelators to prepare strong and thixotropic
hydrogels at physiological pH. The addition of calcium chloride to
the gelator solutions induces the formation of insoluble salts that
get organized in fibers at a pH close to the physiological one. Physical
characterization of hydrogels was carried out by morphologic evaluation
and rheological measurements and demonstrated that the analyzed hydrogels
are thixotropic, as they have the capability to recover their gel-like
behavior. As these hydrogels are easily injectable and may be used
for regenerative medicine, they were biologically assessed by cell
seeding and viability tests. Human gingival fibroblasts were embedded
in 2% hydrogels; all of the hydrogels allow the growth of encapsulated
cells with a very good viability. The gelator toxicity may be correlated
with their tendency to self-assemble and is totally absent when the
hydrogel is formed