Alendronate-Loaded Modified Drug Delivery Lipid Particles Intended for Improved Oral and Topical Administration.

The present paper focuses on solid lipid particles (SLPs), described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In the current study, we present our most recent advances in the preparation of alendronate (AL)-loaded SLPs prepared by hot homogenization and ultrasonication using various ratios of a self-emulsifying lipidic mixture of Compritol 888, Gelucire 44/14, and Cremophor A 25. The prepared AL-loaded SLPs were investigated for their physicochemical, morphological and structural characteristics by dynamic light scattering, differential scanning calorimetry, thermogravimetric and powder X-ray diffraction analysis, infrared spectroscopy, optical and scanning electron microscopy. Entrapment efficacy and actual drug content were assessed by a validated HPLC method. In vitro dissolution tests performed in simulated gastro-intestinal fluids and phosphate buffer solution pH 7.4 revealed a prolonged release of AL of 70 h. Additionally, release kinetics analysis showed that both in simulated gastrointestinal fluids and in phosphate buffer solution, AL is released from SLPs based on equal ratios of lipid excipients following zero-order kinetics, which characterizes prolonged-release drug systems.

Spin-on end-functional diblock copolymers for quantitative DNA immobilization.

We demonstrate a simple means to covalently bond DNA to both hard (i.e., glass and silicon wafers) and soft (i.e., polymeric) substrates that provides quantitative and precise control of the DNA areal density. The approach is based on spin coating an alkyne-end-functional diblock copolymer, alpha-alkyne-omega-Br-poly( tBA- b-MMA), that self-assembles on both types of substrates as an ordered monolayer and thereby directs alkyne groups to the surface. Azido-functionalized DNA is covalently linked to the alkyne functionalized substrates by means of a "click" reaction between azide and alkyne groups. The density of immobilized DNA can be quantitatively controlled by varying the parameters used for spin-coating the copolymer film, that is, solution concentration and rotational speed, or by varying the copolymer molecular weight. We find the yield of the DNA coupling reaction to be dependent on the nature of the polymer underlying the reactive alkyne functional groups, being higher for more hydrophilic polymers.

"Click-functional" block copolymers provide precise surface functionality via spin coating.

There are few existing methods for the quantitative functionalization of surfaces, especially for polymeric substrates. We demonstrate that alkyne end-functional diblock copolymers can be used to provide precise areal densities of reactive functionality on both hard (e.g., glass and silicon oxide) and soft (i.e., polymeric) substrates. Alkyne functionality is extremely versatile because the resultant functional surfaces are reactive toward azide functional molecules by Sharpless click chemistry. Spin-coated films of alpha-alkyne-omega-Br-poly( tert-butylacrylate- b-methylmethacrylate) (poly( tBA-MMA)) spontaneously self-assemble on the aforementioned substrates to present a surface monolayer of PtBA with a thickness in the range of 1 to 9 nm. The PMMA block physisorbs to provide multivalent anchoring onto hard substrates and is fixed onto polymer surfaces by interpenetration with the substrate polymer. The areal density of alkyne functional groups is precisely controlled by adjusting the thickness of the block copolymer monolayer, which is accomplished by changing either the spin coating conditions (i.e., rotational speed and solution concentration) or the copolymer molecular weight. The reactivity of surface-bound alkynes, in 1,3-dipolar cycloaddition reactions or by so-called "click chemistry", is demonstrated by covalent surface immobilization of fluorescently labeled azides. The modificed surfaces are characterized by atomic force microscopy (AFM), contact angle, ellipsometry, fluorescent imaging and angle-dependent X-ray photoelectron spectroscopy (ADXPS) measurements. Microarrays of covalently bound fluorescent molecules are created to demonstrate the approach and their performance is evaluated by determining their fluorescence signal-to-noise ratios.

Universal iterative strategy for the divergent synthesis of dendritic macromolecules from conventional monomers by a combination of living radical polymerization and irreversible TERminator multifunctional INItiator (TERMINI).

A new synthetic concept named TERMINI that stands for irreversible TERminator Multifunctional INItiator is reported. Suitable combinations of TERMINI and living polymerizations provide access to strategies for the design and synthesis of unprecedented complex molecular and macromolecular architectures from a diversity of commercial monomers. TERMINI represents a masked multifunctional initiator designed to quantitatively and irreversibly interrupt a chain organic reaction or a living polymerization. After demasking, the TERMINI repeat unit enables the quantitative reinitiation, in the presence or absence of a catalyst, of the same or a different living polymerization or a chain organic reaction in more than one direction, thus becoming a branching point. The demonstration of this concept was made by using a combination of metal-catalyzed living radical polymerization (LRP) and (1,1-dimethylethyl)[[1-[3,5-bis(S-phenyl 4-N,N'-diethylthiocarbamate)phenyl]ethenyl]oxy]dimethylsilane as TERMINI, to elaborate a novel iterative divergent method for the synthesis of dendritic macromolecules based on methyl methacrylate (MMA).