Investigation of Microemulsion System for Transdermal Drug Delivery of Amphotericin B

In order to solve the drawback of poor bioavailability by the oral route and infusion-related side effect for Amphotericin B(AmB), microemulsion vehicles composed of isopropyl myristate(IPM), Tween 80, isopropyl alcohol and water for transdermal delivery of AmB were designed. The pseudo-ternary phase diagrams were constructed by the H2O titration method and the structures of the microemulsion were determined by measuring electrical conducti-vities(σ). The diffusion studies of AmB microemulsion were performed via excised rabbit skin on a drug diffusion apparatus. To obtain a high solubization of AmB, three different methods were tested to incorporate AmB into mi-croemulsion. The result suggests adding AmB in the shape of NaOH solution to the O/W blank microemulsion over the phase inversion temperature(PIT) of the emulsifier obtains the maximum drug content(2.96 mg/mL). The pH value of the system could be adjusted to pH8.5 or pH<5.2, in this range AmB molecules converts from aqueous to the hydrophilic shell of the microemulsion droplets, drug precipitate is no more than 5%, and the formulations were corresponding to the characterizations of microemulsion. At pH 5.14, AmB microemulsion with Km 1:1, O/SC 1:9(mass ratio ofoil phase to surfactant/cosurfactant blend), water content 64.6%, drug content (2.93±0.08) mg/mL,showed the maximum permeation rate(3.255±0.64)μg·cm-2·h-1,which is stable for a long time.     

磁性纳米颗粒在生物医学领域中的应用

磁性纳米颗粒作为一种新型纳米材料,在许多领域,特别是在生物医药、生物工程等方面具有广阔的应用前景.本文着重论述了近年来磁性纳米颗粒在生物分离、靶向给药、热疗以及磁共振成像对比剂等方面的应用,并对其应用前景进行了展望.     

Alginate-magnesium aluminum silicate films for buccal delivery of nicotine

Sodium alginate-magnesium aluminum silicate (SA-MAS) dispersions with nicotine (NCT) were prepared at different pHs and characterized for the particle size and zeta potential, NCT adsorbed by MAS, and flow behavior before film casting. The physicochemical properties, NCT content, in vitro bioadhesive property, and NCT release and permeation of the NCT-loaded SA-MAS films were investigated. This study showed that incorporation of NCT into the SA-MAS dispersions caused a change in particle size and flow behavior and that NCT could be adsorbed by MAS. The formation of protonated NCT at acidic and neutral pHs could interact with negatively charged MAS via an electrostatic force, resulting in the formation of NCT-MAS flocculates/complexes that could act as microreservoirs in the films. The NCT-loaded SA-MAS films prepared at pH 5 yielded the highest NCT content due to non-significant loss of NCT during drying. Moreover, pH of the preparation also affected the crystallinity and thermal properties of the films. The NCT release and permeation across the mucosal membrane of the films could be described using a matrix diffusion controlled mechanism. In addition, the NCT-loaded SA-MAS films also possessed a bioadhesive property for adhesion to the mucosal membrane. This finding suggests that the NCT-loaded SA-MAS films composed of numerous NCT-MAS complexes as microreservoirs demonstrated a strong potential for use as a buccal delivery system.     

Surface miscibility of EPC/DOTAP/DOPE in binary and ternary mixed monolayers

Surface pressure (π)-molecular area (A) curves were used to characterize the packing of pseudo-ternary mixed Langmuir monolayers of egg phosphatidylcholine (EPC), 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and L-α-dioleoyl phosphatidylethanolamine (DOPE). This pseudo-ternary mixture EPC/DOPE/DOTAP has been successfully employed in liposome formulations designed for DNA non-viral vectors. Pseudo-binary mixtures were also studied as a control. Miscibility behavior was inferred from π-A curves applying the additivity rule by calculating the excess free energy of mixture (ΔG(Exc)). The interaction between the lipids was also deduced from the surface compressional modulus (C(s)(-1)). The deviation from ideality shows dependence on the lipid polar head type and monolayer composition. For lower DOPE concentrations, the forces are predominantly attractive. However, if the monolayer is DOPE rich, the DOTAP presence disturbs the PE-PE intermolecular interaction and the net interaction is then repulsive. The ternary monolayer EPC/DOPE/DOTAP presented itself in two configurations, modulated by the DOPE content, in a similar behavior to the DOPE/DOTAP monolayers. These results contribute to the understanding of the lipid interactions and packing in self-assembled systems associated with the in vitro and in vivo stability of liposomes.     

General Route to Multifunctional Uniform Yolk/Mesoporous Silica Shell Nanocapsules: A Platform for Simultaneous Cancer‐Targeted Imaging and Magnetically Guided Drug Delivery

Hollow mesoporous SiO₂ (mSiO₂) nanostructures with movable nanoparticles (NPs) as cores, so‐called yolk‐shell nanocapsules (NCs), have attracted great research interest. However, a highly efficient, simple and general way to produce yolk‐mSiO₂ shell NCs with tunable functional cores and shell compositions is still a great challenge. A facile, general and reproducible strategy has been developed for fabricating discrete, monodisperse and highly uniform yolk‐shell NCs under mild conditions, composed of mSiO₂ shells and diverse functional NP cores with different compositions and shapes. These NPs can be Fe₃O₄ NPs, gold nanorods (GNRs), and rare‐earth upconversion NRs, endowing the yolk‐mSiO₂ shell NCs with magnetic, plasmonic, and upconversion fluorescent properties. In addition, multifunctional yolk‐shell NCs with tunable interior hollow spaces and mSiO₂ shell thickness can be precisely controlled. More importantly, fluorescent‐magnetic‐biotargeting multifunctional polyethyleneimine (PEI)‐modified fluorescent Fe₃O₄@mSiO₂ yolk‐shell nanobioprobes as an example for simultaneous targeted fluorescence imaging and magnetically guided drug delivery to liver cancer cells is also demonstrated. This synthetic approach can be easily extended to the fabrication of multifunctional yolk@mSiO₂ shell nanostructures that encapsulate various functional movable NP cores, which construct a potential platform for the simultaneous targeted delivery of drug/gene/DNA/siRNA and bio‐imaging.     

Guanidinoamidized linear polyethyleneimine for gene delivery

Guanidine was introduced to low molecular weight linear polyethyleneimine(LPEI) via amide groups, to explore the effect of both guanidine degree and pendant chain length on its transfection behavior. The resulting guanidinoamidized LPEIs(GLPEIs) could dramatically reduce LPEI's toxicity, enhance its DNA-packaging capability, cellular uptake and therefore transfection efficiency. These polyplexes were taken up very efficiently via caveolae-mediated endocytosis and their transfection efficiencies in ovarian cancer cells were significantly improved compared to native LPEI10 k polyplexes. Among these GLPEIs, LPEI-C3-G100 showed higher DNA affinity even than LPEI25 k and the highest transfection efficiency, probably due to the optimization of polymer chain flexibility. Of notice, LPEI-C3-G100 polyplexes could more effectively accumulate into cytoplasm than LPEI25 k, although the transfection efficiency of LPEI-C3-G100 polyplexes was not superior to that of LPEI25 k polyplexes, which would be probably attributed to the more efficient release of LPEI25 k polyplexes than LPEI-C3-G100 polyplexes in the cytoplasm.     

Drug delivery from hydrophobic-modified mesoporous silicas: Control via modification level and site-selective modification

Dimethylsilyl (DMS) modified mesoporous silicas were successfully prepared via co-condensation and post-grafting modification methods. The post-grafting modification was carried out by the reaction of the as-synthesized MCM-41 material (before CTAB removal) with diethoxydimethylsinale (DEDMS). N₂ adsorption-desorption and ²⁹Si MAS NMR characterization demonstrated that different amount of DMS groups were successfully incorporated into the co-condensation modified samples, and the functional DMS groups were placed selectively on the pore openings and external pore surfaces in the post-grafting modified samples. Subsequently, the controlled drug delivery properties from the resulting DMS-modified mesoporous silicas were investigated in detail. The drug adsorption experiments showed that the adsorption capacities were mainly depended on the content of silanol group (CSG) in the corresponding carriers. The in vitro tests exhibited that the incorporation of DMS groups greatly retarded the ibuprofen release rate. Moreover, the ibuprofen release profiles could be well modulated by varying DMS modification levels and site-selective distribution of functional groups in mesoporous carriers.