Dino Aquilano

Cyclodextrin-based nanosponges encapsulating camptothecin: Physicochemical characterization, stability and cytotoxicity

Camptothecin (CAM), a plant alkaloid and a potent antitumor agent, has a limited therapeutic utility because of its poor aqueous solubility, lactone ring instability and serious side effects. Cyclodextrin-based nanosponges (NS) are a novel class of cross-linked derivatives of cyclodextrins. They have been used to increase the solubility of poorly soluble actives, to protect the labile groups and control the release. This study aimed at formulating complexes of CAM with three types of beta-cyclodextrin NS obtained with different cross-linking ratio (viz. 1:2, 1:4 and 1:8 on molar basis with the cross-linker) to protect the lactone ring from hydrolysis and to prolong the release kinetics of CAM. Crystalline (F(1:2), F(1:4) and F(1:8)) and paracrystalline NS formulations were prepared. XRPD, DSC and FTIR studies confirmed the interactions of CAM with NS. XRPD showed that the crystallinity of CAM decreased after loading. CAM was loaded as much as 21%, 37% and 13% w/w in F(1:2), F(1:4) and F(1:8), respectively while the paracrystalline NS formulations gave a loading of about 10% w/w or lower. The particle sizes of the loaded NS formulations were between 450 and 600nm with low polydispersity indices. The zeta potentials were sufficiently high (-20 to -25mV) to obtain a stable colloidal nanosuspension. The in vitro studies indicated a slow and prolonged CAM release over a period of 24h. The NS formulations protected the lactone ring of CAM after their incubation in physiological conditions at 37 degrees C for 24h with a 80% w/w of intact lactone ring when compared to only around 20% w/w of plain CAM. The cytotoxicity studies on HT-29 cells showed that the CAM formulations were more cytotoxic than plain CAM after 24h of incubation.

Encapsulation of Acyclovir in new carboxylated cyclodextrin-based nanosponges improves the agent's antiviral efficacy

Cyclodextrin-based nanosponges (NS) are solid nanoparticles, obtained from the cross-linking of cyclodextrins that have been proposed as delivery systems for many types of drugs. Various NS derivatives are currently under investigation in order that their properties might be tuned for different applications. In this work, new carboxylated cyclodextrin-based nanosponges (Carb-NS) carrying carboxylic groups within their structure were purposely designed as novel Acyclovir carriers. TEM measurements revealed their spherical shape and size of about 400 nm. The behaviour of Carb-NS, with respect to the incorporation and delivery of Acyclovir, was compared to that of NS, previously investigated as a drug carrier. DSC, XRPD and FTIR analyses were used to investigate the two NS formulations. The results confirm the incorporation of the drug into the NS structure and NS-Acyclovir interactions. The Acyclovir loading into Carb-NS was higher than that obtained using NS, reaching about 70% (w/w). In vitro release studies showed the release kinetics of Acyclovir from Carb-NS to be prolonged in comparison with those observed with NS, with no initial burst effect. The NS uptake into cells was evaluated using fluorescent Carb-NS and revealed the nanoparticle internalisation. Enhanced antiviral activity against a clinical isolate of HSV-1 was obtained using Acyclovir loaded in Carb-NS.

Theoretical equilibrium and growth morphology of CaCO3 polymorphs. I. Aragonite

Abstract Periodic bond chain (PBC) analysis is performed using a potential function fitted to elastic, structural and vibrational properties of aragonite. The resulting equilibrium form of the crystal, bounded by six forms having F character, is dominated by {0 1 1}, {1 1 0} and {1 0 2}, other forms being {1 1 1}, {0 1 0} and {0 0 1}, the corresponding specific surface energy γ has a mean value of ≈940erg/cm 2 . The theoretical growth shape is defined by five F-forms: {1 1 0}, {0 1 0}, {0 1 1}, {0 0 1}, {1 0 2} and a stepped one, {0 2 1}. Its habit depends on what value of the attachment energy of {0 1 1} is considered. The agreement between the theoretical growth morphology and that of natural crystals is not fully satisfactory: as a matter of fact three out of the eight forms bounding the averaged natural morphology (i.e., {1 1 1}, {0 1 2} and {1 2 1}) are missing in the theoretical growth morphology. From the observation of the natural gypsum/aragonite epitaxy, a simple model is proposed to explain the striking morphological difference between the pseudo-symmetrical zones [0 1 0] and [1 1 0] in natural aragonite crystals. The variation on the attachment energy of {0 1 0}, induced by water adsorption, improves the fit between theory and observation around these zones, especially when the distribution of their vicinal faces is considered. The same reasoning on water adsorption is extended to the specific surface energy of the crystal: a theoretical value of 330 erg/cm 2 is calculated for γ erystal/water of the face (0 1 0).

Self-assembled nanocrystals of barium carbonate in biomineral-like structures

“Silica Biomorphs” are self-assembled nanocrystals of barium carbonate that form in silica-rich environments. Their morphologies are highly reminiscent of the shapes of primitive life (discovered in Archean cherts), but the precipitates are clearly inorganic and form without intervention of any organic material. The concept of morphology and symmetry has always been used to divide the world into two large groups: the realm of the inanimate and the realm of the living. The object of this study is not to debate the truthfulness of the microfossils, but to understand the laws that control the formation and the shape of polycrystalline structures and to underline the false notion that the living and abiotic realms can be distinguished on the basis of their morphology.

Growth morphology of polar crystals: A comparison between theory and experiment in sucrose

Abstract The theoretical growth morphology of sucrose has been deduced by means of the theory of Hartman and Perdok. Only hydrogen bonds are considered to build up the periodic bond chains. The forms with F character are the following: {100}, {001}, {101}, {110} {110}, {011}, {011}, {111} and {111}. A comparison is made between theoretical and experimental morphology of sucrose crystals grown from pure aqueous solutions.

The competition between {} cleavage and {} steep rhombohedra in gel grown calcite crystals

Abstract Calcite crystals have been obtained from supersaturated solutions diffusing both in agarose and Na-metasilicate gels. Crystal morphology in agarose is characterized mainly by spherulites grown around solid gel impurities and terminated by the cleavage {1 0 1 4} rhombohedron. Grown from Na-metasilicate gel, {1 0 1 4} and {0 1 1 2} rhombohedra compete according to the influence of pH and of the acidifying agent, HCl or CH3COOH, the latter favouring the appearance of the {0 1 1 2} form.

Growth of sucrose crystals and tapering effect studied by holographic interferometry

Effects of dopant raffinose on the growth of sucrose crystals are studied by means of holographic interferometry. By the distribution of hologram fringes the selective doping effect is measured on {100}, {110}, and {110} forms. An interpretation is put forward for the tapering effect in wedge shaped crystals.

Equilibrium and growth forms of sucrose crystals in the {h0l} zone: 1. Theoretical treatment of {101}-d form

Abstract Observed {h0l} growth forms of the sucrose crystal are compared with calculated ones, on the basis of attachment energy plots. Agreement is found for all forms only if a modification of character of the {101}-d face is taken into consideration. Calculation of equilibrium and growth forms have been carried out using two potential for dispersion and hydrogen bond energy respectively. The same method is applied for studying the spiral growth shape on the (101) face and its field of validity is discussed: at low driving force values, the attachment energy at the steps is the relevant energy, determining the shape of spirals on the (101) face of sucrose.

Growth morphology of weddellite CaC2O4 · 2x H2O

Weddellite CaC2O4 · 2x H2O (0 < x < 5 zeolite water fraction) occurs as a mineral of geological and biological genesis (renal lithiasis). Its morphology has been studied from the point of view of the Hartman-Perdok theory: in consequence the [001] and 〈111〉 PBCs have been identified. The theoretical growth morphology consists of two F forms ({011} and {110}) and one S {100}. Natural and synthetic crystals do not show {110}, but present only {011} and {100} very well developed. In order to explain this actual morphology the PBC analysis has been integrated by the study of the surface structure and composition, taking into account qualitatively the interactions between the growth-surfaces and the mother solution. Finally, a novel method of synthesis of weddellite by slow diffusion through gel is proposed.

Twin growth of sucrose crystals

Abstract A crystallographic and kinetic approach is given to understand twinning of sucrose crystals. The twin law is redefined and original composition planes for twinning (OCP) are found consistent with experiments. The elongation parameter Π is defined as a function of supersaturation and growth time. The calculated and measured Π values compare favourably both in pure solution growth and in the presence of low concentrations of raffinose. Experiments stress that the polar character of sucrose is determining both the crystallographic properties and kinetic behaviour of twins.