Rosario Palumbo

Compatibilized poly(ε-caprolactone)/poly(L-lactide) blends for biomedical uses

A binary poly(L-lactide)/poly(e-caprolactone) (PLLA/PCL) (70/30 w/w) blend and a ternary PLLA/PCL/PLLA-PCL-PLLA blend of the same composition which contains 4 wt.-% of a triblock PLLA-PCL-PLLA copolyester as compatibilizing agent were prepared by melt mixing at 200°C. Investigation of the thermal and mechanical properties of the blends and scanning electron microscopy of their fracture surfaces showed in the case of the ternary blend a better state of dispersion of PCL in the PLLA matrix and an improved toughness.

Biodegradable microspheres of novel segmented poly(ether-ester-amide)s based on poly(ε-caprolactone) for the delivery of bioactive compounds

A novel class of multiblock poly(epsilon-caprolactone)-based polymers containing hydrophilic trioxyethylene segments and potentially relevant to the delivery of drugs is described in this work. L-phenylalanine residues may also be inserted into the hydrophilic blocks to generate peptide bonds susceptible to enzymatic attack. The investigated polymers were poly(ether-ester-amide)s (PEEAs) obtained by a two-step polymerization procedure from OH-end capped low molecular weight poly(epsilon-caprolactone), sebacoyl chloride and either 4,7,10-trioxa-1,13-tridecanediamine (PEEA1) or 1,13-di(L-phenylalaninamido)-4,7,10-trioxatridecane (PEEA2). PEEAs were characterized by 1H-NMR spectroscopy, differential scanning calorimetry, gel permeation chromatography and were tested for their suitability in producing microspheres. Particles obtained by the single emulsion-solvent evaporation technique were regular and smooth (SEM analysis) showing a monomodal distribution of dimensions. To assess the potentiality of PEEAs in the oral delivery of drugs, three model compounds with different pKa and solubilities--diclofenac, nicardipine and dicumarol--were encapsulated within PEEA microspheres. For the sake of comparison, microspheres prepared from poly(epsilon-caprolactone) (PCL) with a molecular weight similar to PEEAs were also prepared and tested. The release of diclofenac from all the microspheres was very rapid (100% released within 2 h) whereas nicardipine release was slower and biphasic. The initial phase approximated a near zero-order release, being the fraction of nicardipine released after 8 h from PEEA microspheres higher with respect to PCL particles (about 70 vs. 30%). This result was ascribed to the lower crystallinity of PEEAs with respect to PCL which results in a facilitated access of water molecules through the polymer matrix. The lipophilic-unionizable dicumarol was released from PEEA microspheres at a very slow rate. Therefore, dicumarol-loaded PEEA2 microspheres allowed the study of the influence on the release rate of the insertion into the polymer chain of enzymatically degradable bonds. PEEA2 microspheres released dicumarol at the same rate in a medium with or without the proteolitic enzyme alpha-chymotrypsin. Although the insertion of an isolated amino acid was not sufficient to confer enzyme susceptibility to the polymer, the distinctive properties of PEEAs make their use very attractive in the field of controlled release.

Nanocapsules Based on Linear and Y-Shaped 3-Miktoarm Star-Block PEO-PCL Copolymers as Sustained Delivery System for Hydrophilic Molecules

Well-defined amphiphilic Y-shaped miktoarm star-block copolymers of PEO and PCL were synthesized by ring-opening polymerization of ε-caprolactone initiated by a PEO-bound lysine macroinitiator. The copolymers were characterized by (1)H NMR, SEC, DSC, and WAXD techniques. Separate PCL and PEO crystalline phases occur in melt-crystallized copolymers when their segmental lengths were comparable and the PCL content was ≤80 wt %. Self-assembling of these copolymers in aqueous medium led to nanoaggregates with low critical aggregation concentration values (0.35 to 1.6 mg·L(-1)) and size depending on composition. Despite the fact that copolymers were not prone to self-organize in vesicles, once processed by a novel w/o emulsion-melting-sonication technique, they gave nanocapsules with a water core and a hydrophilic surface. A macromolecular fluorescent dye was effectively loaded and released at sustained rate by optimizing nanocapsule formulation. The results demonstrate that amphiphilic block copolymers can be assembled in different kinds of nanomorphologies independently of their hydrophilic/hydrophobic balance and architecture through specifically designed preparation techniques.

Micelles based on amphiphilic PCL-PEO triblock and star-shaped diblock copolymers: Potential in drug delivery applications.

In this work, the potential in drug nanodelivery of micelles made from poly(epsilon-caprolactone) (PCL) and poly (ethyleneoxide) (PEO) copolymers with triblock and star-diblock architectures was explored. Linear and 4-arm star-shaped PCL macromers with two or four --OH end groups were prepared by ring-opening polymerization of CL and condensed with alpha-methoxy-omega-carboxy-PEO. The resulting amphiphilic copolymers were characterized by (1)H NMR, size exclusion chromatography, and differential scanning calorimetry. Separate PCL and PEO crystalline phases were observed for both copolymers. Copolymers self-assembled in water giving critical association concentrations in the range 0.010-0.023 mg/mL. Micelles with a size of 32-45 nm were prepared by dialysis and characterized for hydrodynamic diameter and surface charge. Their potential as nanocarriers in drug delivery applications was evaluated too. Micelles were nontoxic to both Red blood cells and HeLa cells. Complement activation experiments indicated that micelles can escape the reticuloendothelial system once intravenously injected. Finally, a different uptake on HeLa cells was found for micelles obtained from triblock and star-shaped copolymers.

Segmented poly(ether-ester-amide)s based on poly(L, L-lactide) macromers

Abstract Segmented poly(ether–ester–amide)s (PEEAs) were obtained from sebacoyl chloride (SEB), α,ω-hydroxyl terminated poly( l , l -lactide) (PLLA) or PLLA–PEG–PLLA macromers and the hydrophilic diamines 4,7,10-trioxa-1,13-tridecanediamine ( 1 ) and 3,6,9,12,15-pentoxa-1,17-heptadecanediamine ( 2 ) or diamide–diamines derived from 1 and 2 by inserting Gly-Phe or Gly-Val-Phe sequences. The molar ratio macromer/SEB/diamine was 1/2/1. The PEEAs were characterized by i.r. and 1 H n.m.r spectroscopy and S.E.C. They are soluble in polar organic solvents and insoluble in water, but show equilibrium water absorptions up to 21.0% by wt. All PEEAs are semicrystalline, as shown by d.s.c. and WAXS techniques, with T m s ranging from 110 to 135°C. D.s.c. and d.m.t.a. showed a single T g in the temperature range 31–53°C. Evidence of microphase separation was obtained only for aminoacids containing PEEAs by t.e.m.. Biocompatibily was assessed for selected polymers checking the viability and growth of Caco-2 cells on polymer films.

New segmented copolymers containing poly(ϵ-caprolactone) and etheramide segments for the controlled release of bioactive compounds

Segmented poly(ether-ester-amide)s (PEEAs) derived from poly(epsilon-caprolactone) oligomers, sebacoyl chloride, hydrophilic diamide-diamines based on short sequences of ethylenoxy groups and containing amino acids, were used to produce matrix systems intended for the delivery of metronidazole in the periodontal pocket. PEEAs are soluble in chloroform and insoluble in water and show M(n) values in the range 8.5-18.6 kDa. The melting temperatures (53-59 degrees C) are close to that of poly(epsilon-caprolactone) (PCL) with a similar M(n). The water absorption of PEEAs is improved if compared with that of pure PCL and depends on both the length of oxyethylene sequences and the amino acid number, as well as on copolymer composition. Loaded-films containing 20% (w/w) of metronidazole were prepared by compression-molding. The release rate was diffusive in the first stage, whereas also other mechanisms, probably polymer degradation, contributed to the slower second phase. The rate of medium penetration within the film depended on PEEA hydrophilicity and crystallinity and was the main determinant governing the drug release rate. The opportunity to control effectively drug release rates by modulating the composition, and in turn the properties, of PEEAs is an attracting feature for their use in a number of drug delivery systems.

Aromatic poly(benzoxazole)s from multiring diacids containing (phenylenedioxy)diphenylene or (naphthalenedioxy)diphenylene groups: Synthesis and thermal properties

Poly(arylether benzoxazole)s (PAEBOs) were prepared from a series of fully aromatic dicarboxylic acids containing (phenylenedioxy)diphenylene or (naphthalenedioxy) diphenylene groups and 3,3′-dihydroxy-4,4′-diaminobiphenyl (I) or 4-4′-(hexafluoroisopropylidene)bis(2-aminophenol) (II) through high-temperature direct polycondensation. A phosphorous pentoxide/methanesulfonic acid mixture or trimethylsilylpolyphosphate was used as a condensing agent. All the PAEBOs were amorphous and soluble in strong acids, and those derived from II were also readily soluble in polar organic solvents. Flexible films were cast from their chloroform solutions. The PAEBOs showed inherent viscosity values of 0.68–2.06 dL/g (CH3SO3H, T = 30 °C, c = 0.15 g · dL−1). Thermal analysis indicated glass-transition temperatures ranging from 236 to 270 °C and thermal stability (5% weight loss) in nitrogen up to 526 °C.

Synthesis and thermal properties of poly(amideimide)s based on tricarboxylic acid anhydrides containing aryloxy groups

Thermostable poly(amideimide)s (PAIs) were synthesized according to a ‘one-pot/two-step’ direct polycondensation of flexible aromatic diamines with monoesters of isomeric tricarboxylic acid anhydrides containing an aryloxy group or with the monoesters of trimellitic anhydride (TMA). The prepared PAIs have inherent viscosity values of 0.46–0.95 dl g−1, are soluble in strongly polar aprotic solvents and form tough and transparent films. The molecular structure of the polymers was investigated by Fourier transform infrared and 1H and 13C nuclear magnetic resonance spectroscopy. A constitutional disorder due to a random sequence of amide and imide groups was found. Measurements by wide-angle X-ray diffraction indicated that the prepared PAIs are amorphous. The thermal behaviour was studied by differential scanning calorimetry and dynamic thermogravimetric analysis. The glass transition temperatures (Tg) of the PAIs obtained from monoesters of tricarboxylic acid anhydrides containing an aryloxy group range between 262 and 213°C, and are lower than those of the corresponding PAIs derived from TMA. The prepared PAIs have high thermal resistance in nitrogen as shown by their temperatures of 10% of weight loss (Td), which are higher than 500°C. Both Tg and Td depend on the orientation of the aryloxy group in the tricarboxylic acid anhydride moiety.

Synthesis and physical behaviour of poly(amidoether) block copolymers

Abstract Random multiblock polyamide-polyether copolymers containing 13–30 wt% of polyether have been synthesized by a two-step procedure from adipoyl chloride, 1,6-diaminohexane and two α,ω-dihydroxy-poly(ethylene oxides) having M n =600 and 1550 g mol−1. The compositions and architectures of the copolymers were determined by elemental analysis and by 1H nuclear magnetic resonance spectroscopy. Thermal analysis showed the presence of a main crystalline component that thermal parameters indicated as polyamidic. Transport properties were analysed using water vapour as permeant; they indicated a permeability much higher than in polyamide-6,6 and suggested the presence in the amorphous component of a domain structure in which polyether volume elements are segregated from a polyamide matrix. Thermomechanical and dynamic mechanical analyses suggested that flexible polyether sequences increase the overall flexibility of the copolymer chains.

Poly(amideimide)s based on diamines containing bisaryloxy groups: structure-properties relationships

Abstract A series of random poly(amideimide)s (PAIs) were prepared from 1,2,4-benzenetricarboxylic acid monoesters and multi-ring diamines containing bisaryloxy groups by a ‘one pot’ method using the triphenylphosphite/pyridine system. The diamines differ because of the para or meta catenation and because of the presence of lateral substituents or bulky isopropylidene or perfluoroisopropylidine groups connecting two phenyl rings. The prepared PAIs were characterized by Fourier transform infra-red and 1H nuclear magnetic resonance spectroscopy. Thermal analysis and X-ray diffraction experiments indicated that all PAIs ‘as polymerized’, are amorphous and that polymers having a prevailing para-orientation and no substituents crystallize upon thermal treatments. The glass transition temperatures (Tgs) determined by differential scanning calorimetry and dynamic mechanical thermal analysis, range between 178°C and 253°C. Both the Tg and the solubility, in polar aprotic solvents, are strongly affected by the chemical structure of the polymers. Flexible and tough films were obtained by solution casting or, in the case of amorphous PAIs, by compression moulding. The PAIs investigated exhibit thermostability-10% weight loss at T ≥ 495°C-as shown by dynamic thermogravimetric analysis.