Miao Li

Peking University, Beijing, Beijing Shi, China

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Publications (11)22.38 Total impact

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    ABSTRACT: Iontophoresis is an important approach to improve transdermal drug delivery. However, The transdermal enhancement mechanism of iontophoresis was not well known. The relationship between the physicochemical properties of drugs and the transdermal enhancement effect of iontophoresis was revealed in this study. Non-steroidal anti-inflammatory drugs (NSAIDs) were used as the models, including aspirin, ibuprofen and indomethacin. Their oil-water partition coefficients were measured. The carbomer-based hydrogels of them were prepared. Iontophoresis significantly enhanced in vitro transdermal delivery across the rat skins. Strong lipophilicity could lead to high permeation of drugs. However, the dissociation extent (indicated as pKa) of drugs was the key factor to determine the transdermal enhancement effect of iontophoresis. The more dissociation the drugs were, the higher the transdermal enhancement effect of iontophoresis. The drug-loaded hydrogels combined with iontophoresis improved the treatment of rat raw's inflammatory syndrome. Iontophoresis significantly improved the drugs penetrating into the hypodermis, dermis and epidermis, more deeply than the application of drugs alone according to the experimental result of 5-carboxylfluorescein hydrogels. Iontophoresis led to the unordered arrangement of skin intercellular lipids, the significantly increased flowability and loose stratum corneum structure. Iontophoresis is a promising approach to improve transdermal drug delivery with safety and high efficiency.
    International journal of pharmaceutics 03/2014; · 2.96 Impact Factor
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    ABSTRACT: The aim of the present study was to develop the novel immediate-controlled release (ICR) tablets of isosorbide-5-mononitrate (5-ISMN) composed of an osmotic pump tablet core coated with an immediate-release layer. The novel ICR tablets of 5-ISMN could release drug quickly and continuously through a semi-permeable membrane (SPM) composed of ethylcellulose (EC)/polyethylene glycol (PEG) 4000 and cellulose acetate (CA)/PEG4000. Release tended to decrease with storage time. However, the drug release rates changed little for the SPM composed of EC/PVP K30. The weight loss test also confirmed these results. The major release mechanism was diffusion according to the Higuchi equation. The relative bioavailability of the ICR tablets compared to the reference formulation in the single and multiple dose regiments were 90.9 and 111.2%, respectively. They were both bioequivalent to the reference formulation. In vitro-in vivo correlation (IVIVC) studies demonstrated that the dissolution in vitro simulated the absorption in vivo well. In general, 5-ISMN ICR tablets composed of an osmotic pump tablet core and an immediate-release layer may be promising in providing immediate and constant drug delivery with minimum fluctuations during long storage time.
    Pharmazie 02/2014; 69(2):109-16. · 0.96 Impact Factor
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  • Lina Du, Miao Li, Yiguang Jin
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    ABSTRACT: A first-order derivative UV spectrophotometric method was developed to determine triclosan, a broad-spectrum antimicrobial agent, in health care products containing fragrances which could interfere the determination as impurities. Different extraction methods were compared. Triclosan was extracted with chloroform and diluted with ethanol followed by the derivative spectrophotometric measurement. The interference of fragrances was completely eliminated. The calibration graph was found to be linear in the range of 7.5-45 microg x mL(-1). The method is simple, rapid, sensitive and proper to determine triclosan in fragrance-containing health care products.
    Pharmazie 10/2011; 66(10):740-3. · 0.96 Impact Factor
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    ABSTRACT: Combination anti-HIV therapy is important for AIDS treatment. A bolaamphiphilic prodrug, zidovudine-phosphoryl-deoxycholyl didanosine (ZPDD), was synthesized, combining zidovudine (AZT) and didanosine (ddI) in one molecule. As one lipid derivative of nucleosides, ZPDD showed special solubility with free soluble in chloroform and tetrahydrofuran but was slightly soluble in cyclohexane. The amphiphilicity of ZPDD was shown according to the monolayers at the air-water interface. ZPDD self-assembled to the spherical vesicles in water with 174 nm in size and -31.3 mV of zeta potential. The stability of assemblies depended on pH because the phosphoryl zidovudine group could release hydrogen ions. ZPDD was rapidly degraded to AZT in the plasma and tissues of mice. ZPDD self-assemblies had high anti-HIV activity in vitro with the half effective concentration (EC₅₀) of 5 nM. ZPDD self-assemblies may be targeting macrophages since ZPDD was found in macrophage-rich tissues in vivo and rapidly released AZT in the targeted tissues after intravenous administration to mice. The bioavailability of ZPDD was 90.5% and 30.8% for the intraperitoneal and oral administrations compared with the venous route. The self-assemblies of bolaamphiphilic prodrugs could simultaneously deliver two types of drugs to targeted tissues and would become a promising nanomedicine.
    Molecular Pharmaceutics 06/2011; 8(3):867-76. · 4.57 Impact Factor
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    International Journal of Pharmaceutics - INT J PHARM. 01/2010; 397:231-231.
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    ABSTRACT: An amphiphilic prodrug of anti-HIV nucleoside analogue, cholesteryl-phosphonyl zidovudine (CPNZ) was synthesized. An aqueous suspension containing CPNZ self-assemblies was obtained through injecting the ethanol solution of CPNZ and cholesteryl succinyl poly(ethylene glycol) 1500 (20:1, mol/mol) into water under agitation. Hydrophobic interaction may be the driving force of molecular self-assembly. The self-assemblies were nanoscale with approximately 100nm in size, and remained stable for a long time. Degradation of CPNZ self-assemblies was investigated in various environments including buffered solutions, plasma and rabbit tissue homogenates. CPNZ was degraded very slowly in neutral solutions but rapidly in various plasma with the half-lives (t(1/2)) of less than 20h. Tissue homogenates degraded CPNZ with varied rates depending on enzyme activity. CPNZ self-assemblies showed potent anti-HIV activity on MT4 cell model, the anti-HIV 50% effective concentration (EC(50)) of which was 1nM, only equal to 1/5 of AZT EC(50). CPNZ was rapidly eliminated from circulation and distributed into the mononuclear phagocyte system (MPS) including liver, spleen and lung after bolus intravenous administration of CPNZ self-assemblies followed slowly elimination. The possible products include AZT-5'-H-phosphonate, AZT and their derivatives. The MPS-targeted effect and high anti-HIV activity of CPNZ self-assemblies make them become a promising self-assembled drug delivery system (SADDS).
    International journal of pharmaceutics 08/2009; 381(1):40-8. · 2.96 Impact Factor
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    ABSTRACT: Self-assembled drug delivery systems (SADDS) were designed in the paper. They can be prepared from the amphiphilic conjugates of hydrophilic drugs and lipids through self-assembling into small-scale aggregates in aqueous media. The outstanding characteristic of SADDS is that they are nearly wholly composed of amphiphilic prodrugs. The self-assembled nanoparticles (SAN) as one of SADDS had been prepared from the lipid derivative of acyclovir (SGSA) in the previous paper. They were further studied on the properties and the in vitro/in vivo behavior in this paper. The SAN kept the physical state stable upon centrifugation or some additives including some inorganic salts, alkaline solutions, surfactants and liposomes except for HCl solution, CaCl(2) solution and animal plasma. Autoclave and bath heat for sterilization hardly influenced the SAN. However, gamma-irradiation strongly destroyed the structure of SAN and SGSA was degraded. SGSA in SAN showed good stability in weak acidic or neutral buffers although it was very sensitive to alkaline solutions and carboxylester enzymes, the half-lives (t(1/2)) of which in the buffer at pH 7.4, the alkaline solution at pH 12.0, pig liver carboxylester enzyme solution, rabbit plasma, and rabbit liver tissue homogenate were 495, 21, 4.7, 25 and 8.7 h, respectively. Compared with SGSA in a disordered state, the specific bilayer structures of SAN could protect SGSA from hydrolysis through hiding the sensitive ester bonds. The SAN showed hemolytic action because the amphiphilic SGSA could insert into rabbit erythrocyte membranes. Both the high concentration of SGSA in samples and the long incubation time improved hemolysis. No hemolysis was observed if the additional volume of the SAN was less than 10% of rabbit whole blood in spite of the high concentration of SGSA. Plasma proteins could interfere the interaction between the SAN and erythrocytes by binding the SAN. The in vitro antiviral activity of acyclovir SAN was limited possibly because of the weak hydrolysis of SGSA in Vero cells, and the SAN showed a little cell toxicity possible due to the amphiphilicity of SGSA. A macrophage cell line of QXMSC1 cells showed uptake of the SAN but not significantly. The SAN were rapidly removed from blood circulation after bolus iv administration to rabbits with the very short distribution t(1/2) (1.5 min) and the elimination t(1/2) (47 min). The SAN were mainly distributed in liver, spleen and lung after iv administration, and SGSA was eliminated slowly in these tissues (t(1/2), about 7 h). It would appear that the nanosized SAN were trapped by the mononuclear phagocyte system. SADDS including SAN combine prodrugs, molecular self-assembly with nanotechnology, and hopefully become novel drug delivery approaches.
    International Journal of Pharmaceutics 03/2006; 309(1-2):199-207. · 3.46 Impact Factor
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    ABSTRACT: The long-chain alkyl derivatives of a nucleoside analogue-acyclovir were prepared in the paper. One is stearyl-glycero-succinyl-acyclovir (SGSA) with a single 18-carbon length (C18) alkyl chain. Another is dioctadecyl-aspartate-succinyl-acyclovir (DASA) with double C18 alkyl chains. They were prepared by the esterification of succinyl-acyclovir with the lipids, and sodium salts of them were also prepared. Guanine moieties and alkyl moieties bring the derivatives intermolecular hydrogen bonding and hydrophobic interaction in water separately. The forces are influenced by the number of alkyl chains and the charged state, and determine the solubility and the self-assembly behavior of the derivatives. The double alkyl-chain derivatives (DASA and DASA-Na) formed rigid Langmuir monolayers on air/water surface, while the single alkyl chain derivatives (SGSA and SGSA-Na) did not. However, cholesterol (Chol) could assist SGSA to form rigid monolayers through inserting into the alkyl chains of SGSA to mimic the second alkyl chain. SGSA self-aggregates in water were prepared by the injection method with tetrahydrofuran as solvent. Cuboid-like shape and nanoscale size demonstrated that SGSA self-aggregates were self-assembled nanoparticles. Shape, particle size, zeta potential and phase transition of the nanoparticles were characterized. And they showed an average size of 83.2 nm, a negative surface charge of -31.3-mV zeta potential and a gel-liquid crystalline phase transition of 50.38 degrees C. The formation mechanism of self-assembled nanoparticles was analyzed. Hydrophobic interaction of alkyl chains improves SGSA molecules to form bilayers, and then cuboid-like nanoparticles were obtained by layer-by-layer aggregation based on inter-bilayers hydrogen bonding. However, the charged guanine moieties make SGSA-Na lose the function of hydrogen bonding so that SGSA-Na only forms vesicles in water based on hydrophobic interaction. Strong hydrophobicity and wide-open rigid double alkyl chains of DASA and DASA-Na restrict self-assembly in water media, and no homogeneous suspensions were obtained. Therefore, the molecular self-assembly behavior of the long-chain alkyl derivatives of nucleoside analogues on water surface or in water media is determined by the number of alkyl chains and the charged state.
    Colloids and surfaces B: Biointerfaces 05/2005; 42(1):45-51. · 3.55 Impact Factor
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    ABSTRACT: Pyrocatechol violet (PV), a chelating agent for cupric ions was used to characterize liposomal membrane permeability. After cupric ions were added to PV liposomes, free PV turned into its chelate (PV-Cu), and encapsulated PV kept stable since liposomal membranes prevented metal ions from permeating. After the light scattering background of liposomes and the absorbance of PV were eliminated by the first-order derivative spectrophotometric method, PV-Cu i.e. free PV in liposome suspensions could be determined without separation. The released PV from liposomes could also be determined. Because PV release is relevant to liposomal membrane permeability, PV becomes a marker to characterize the membrane permeability. This new method was simple, rapid, sensitive, and was used to measure the temperature-dependent liposomal membrane permeability in this paper. Dipalmitoylphosphatidylcholine (DPPC) and soybean lecithin liposomes showed the peaks of release at 40 degrees C and 39 degrees C, respectively.
    Journal of Pharmaceutical and Biomedical Analysis 03/2005; 37(2):379-82. · 2.95 Impact Factor
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    [show abstract] [hide abstract]
    ABSTRACT: Self-assembled drug delivery systems (SADDS) were designed in the paper. They can be prepared from the amphiphilic conjugates of hydrophilic drugs and lipids through self-assembling into small-scale aggregates in aqueous media. The outstanding characteristic of SADDS is that they are nearly wholly composed of amphiphilic prodrugs. The self-assembled nanoparticles (SAN) as one of SADDS had been prepared from the lipid derivative of acyclovir (SGSA) in the previous paper. They were further studied on the properties and the in vitro/in vivo behavior in this paper. The SAN kept the physical state stable upon centrifugation or some additives including some inorganic salts, alkaline solutions, surfactants and liposomes except for HCl solution, CaCl2 solution and animal plasma. Autoclave and bath heat for sterilization hardly influenced the SAN. However, gamma-irradiation strongly destroyed the structure of SAN and SGSA was degraded. SGSA in SAN showed good stability in weak acidic or neutral buffers although it was very sensitive to alkaline solutions and carboxylester enzymes, the half-lives ( t1/2) of which in the buffer at pH 7.4, the alkaline solution at pH 12.0, pig liver carboxylester enzyme solution, rabbit plasma, and rabbit liver tissue homogenate were 495, 21, 4.7, 25 and 8.7 h, respectively. Compared with SGSA in a disordered state, the specific bilayer structures of SAN could protect SGSA from hydrolysis through hiding the sensitive ester bonds. The SAN showed hemolytic action because the amphiphilic SGSA could insert into rabbit erythrocyte membranes. Both the high concentration of SGSA in samples and the long incubation time improved hemolysis. No hemolysis was observed if the additional volume of the SAN was less than 10% of rabbit whole blood in spite of the high concentration of SGSA. Plasma proteins could interfere the interaction between the SAN and erythrocytes by binding the SAN. The in vitro antiviral activity of acyclovir SAN was limited possibly because of the weak hydrolysis of SGSA in Vero cells, and the SAN showed a little cell toxicity possible due to the amphiphilicity of SGSA. A macrophage cell line of QXMSC1 cells showed uptake of the SAN but not significantly. The SAN were rapidly removed from blood circulation after bolus iv administration to rabbits with the very short distribution t1/2 (1.5 min) and the elimination t1/2 (47 min). The SAN were mainly distributed in liver, spleen and lung after iv administration, and SGSA was eliminated slowly in these tissues (t1/2, about 7 h). It would appear that the nanosized SAN were trapped by the mononuclear phagocyte system. SADDS including SAN combine prodrugs, molecular self-assembly with nanotechnology, and hopefully become novel drug delivery approaches. © 2005 Elsevier B.V. All rights reserved.