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Dive into the research topics where Yunmei Song is active.

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Featured researches published by Yunmei Song.


Molecular Pharmaceutics | 2009

Dry Hybrid Lipid−Silica Microcapsules Engineered from Submicron Lipid Droplets and Nanoparticles as a Novel Delivery System for Poorly Soluble Drugs

Spomenka Simovic; Peter J Heard; He Hui; Yunmei Song; Frank Peddie; Andrew K. Davey; Ac Lewis; Thomas Rades; Clive A. Prestidge

We report on the fabrication and characterization of dry hybrid lipid-silica nanoparticle based microcapsules with an internal porous matrix structure for encapsulation of poorly soluble drugs, and their delivery properties (in vitro release and lipolysis and in vivo pharmacokinetics demonstrated for indomethacin as a model drug). Microcapsules were prepared by spray drying of Pickering o/w emulsions containing either negatively or positively charged lipophilic surfactant in the oil phase and hydrophilic silica nanoparticles in the aqueous phase. Effective microcapsule formation is critically dependent on the interfacial structure of the nanoparticle containing emulsions, which are in turn controlled by the surfactant charge and the nanoparticle to lipid ratio. Microcapsules (containing 50-85% oil) can be prepared with 10 times fewer silica nanoparticles when a droplet-nanoparticle charge neutralizing mechanism is operative. Cross-sectional SEM imaging has confirmed the internal porous matrix structure and identified pore sizes in the range 20-100 nm, which is in agreement with BET average pore diameters determined from gas adsorption experiments. Differential scanning calorimetry and X-ray diffraction analysis have confirmed that the model drug indomethacin remains in a noncrystalline form during storage under accelerated conditions (40 degrees C, 75% RH). Dissolution studies revealed a 2-5-fold increase in dissolution efficiency and significantly reduced the time taken to achieve 50% of drug dissolution values (> or =2- or 10-fold) for indomethacin formulated as microcapsules in comparison to o/w submicron emulsions and pure drug, respectively. Orally dosed in vivo studies in rats have confirmed superior pharmacokinetics for the microcapsules. Specifically, the fasted state absolute bioavailability (F) was statistically higher (93.07 +/- 5.09%) (p < 0.05) than for aqueous suspension (53.54 +/- 2.91%) and o/w submicron emulsion (64.57 +/- 2.11%). The microcapsules also showed the highest maximum plasma concentration (C(max)) among the investigated formulations (p < 0.05). In vitro lipolysis showed statistically higher (p < 0.05) fasted digestion (75.8% after 5 min) and drug solubilization (98% after 5 min) in digestive products for microcapsules than o/w emulsions. The hybrid lipid-silica microcapsules improve oral absorption by enhancing lipolysis and drug dissolution.


Journal of Controlled Release | 2010

An oral delivery system for indomethicin engineered from cationic lipid emulsions and silica nanoparticles

Spomenka Simovic; He Hui; Yunmei Song; Andrew K. Davey; Thomas Rades; Clive A. Prestidge

We report on a porous silica-lipid hybrid microcapsule (SLH) oral delivery system for indomethacin fabricated from Pickering emulsion templates, where the drug forms an electrostatic complex with cationic lipid present in the oil phase. Dry SLH microcapsules prepared either by spray drying (approximately 1-5 microm) or phase coacervation (20-50 microm) exhibit a specific internal porous matrix structure with pore diameters in the range of 20 to 100 nm. Dissolution studies under sink conditions and in the presence of electrolytes revealed a decreased extent of dissolution; this confirms the lipophilic nature the drug-lipid complex and its location in the oil phase. Orally dosed in-vivo studies in rats showed complete drug absorption and statistically higher fasted state bioavailability (F) (p<0.05) in comparison to aqueous suspensions and o/w submicron emulsions of indomethacin. It is postulated that the SLH microcapsules improve oral absorption via complete solubilisation of drug-lipid electrostatic complexes during enzymatic lipolysis in the GI track.


International Journal of Nanomedicine | 2011

Particle size reduction to the nanometer range: a promising approach to improve buccal absorption of poorly water-soluble drugs

Shasha Rao; Yunmei Song; Frank Peddie; Allan M. Evans

Poorly water-soluble drugs, such as phenylephrine, offer challenging problems for buccal drug delivery. In order to overcome these problems, particle size reduction (to the nanometer range) and cyclodextrin complexation were investigated for permeability enhancement. The apparent solubility in water and the buccal permeation of the original phenylephrine coarse powder, a phenylephrine–cyclodextrin complex and phenylephrine nanosuspensions were characterized. The particle size and particle surface properties of phenylephrine nanosuspensions were used to optimize the size reduction process. The optimized phenylephrine nanosuspension was then freeze dried and incorporated into a multi-layered buccal patch, consisting of a small tablet adhered to a mucoadhesive film, yielding a phenylephrine buccal product with good dosage accuracy and improved mucosal permeability. The design of the buccal patch allows for drug incorporation without the need to change the mucoadhesive component, and is potentially suited to a range of poorly water-soluble compounds.


International Journal of Nanomedicine | 2010

Effects of chitosan coating on physical properties and pharmacokinetic behavior of mitoxantrone liposomes

Jie Zhuang; Qineng Ping; Yunmei Song; Jianping Qi; Zheng Cui

The objective of this work was to evaluate the physical properties and in vivo circulation of chitosan (CH)-coated liposomes of mitoxantrone (MTO). Changes in particle size and zeta potential confirmed the existence of a coating layer on the surface of liposomes. The in vitro release of adsorbed CH from the liposomes was significantly slower than CH solution, indicating the stable interaction between CH and liposomes. The physical stability of the CH-coated liposomes was evaluated by measuring the change in particle size before and after freeze-drying and rehydration. The smallest change was observed when saturated adsorption of CH occurred (0.3%). The sustained release in vitro of MTO from CH-coated liposomes confirmed the increased stability of liposomes. Systemic circulation of CH-coated MTO liposomes was examined. The 0.3% CH-coated liposomes showed the longest circulation time. It could be concluded that the prolonged retention time of the liposomes was closely related with CH coating and its stability effect.


International Journal of Nanomedicine | 2011

Enhanced effect and mechanism of water-in-oil microemulsion as an oral delivery system of hydroxysafflor yellow A

Jianping Qi; Jie Zhuang; Wei Wu; Yi Lu; Yunmei Song; Zhetao Zhang; Jia Jia; Qineng Ping

Background: A microemulsion is an effective formulation for improving the oral bioavailability of poorly soluble drugs. In this paper, a water-in-oil (w/o) microemulsion was investigated as a system for enhancing the oral bioavailability of Biopharmaceutic Classification System (BCS) III drugs. Methods: The microemulsion formulation was optimized using a pseudoternary phase diagram, comprising propylene glycol dicaprylocaprate (PG), Cremophor® RH40, and water (30/46/24 w/w). Results: The microemulsion increased the oral bioavailability of hydroxysafflor yellow A which was highly water-soluble but very poorly permeable. The relative bioavailability of hydroxysafflor yellow A microemulsion was about 1937% compared with a control solution in bile duct-nonligated rats. However, the microemulsion showed lower enhanced absorption ability in bile duct-ligated rats, and the relative bioavailability was only 181%. In vitro experiments were further employed to study the mechanism of the enhanced effect of the microemulsion. In vitro lipolysis showed that the microemulsion was digested very quickly by pancreatic lipase. About 60% of the microemulsion was digested within 1 hour. Furthermore, the particle size of the microemulsion after digestion was very small (53.3 nm) and the digested microemulsion had high physical stability. An everted gut sac model demonstrated that cumulative transport of the digested microemulsion was significantly higher than that of the diluted microemulsion. Conclusion: These results suggested that digestion of the microemulsion by pancreatic lipase plays an important role in enhancing oral bioavailability of water-soluble drugs.


RSC Advances | 2015

Co-delivery of doxorubicin hydrochloride and verapamil hydrochloride by pH-sensitive polymersomes for the reversal of multidrug resistance

Nuannuan Li; Pei Zhang; Chunzhi Huang; Yunmei Song; Sanjay Garg; Yuxia Luan

In this paper, we synthesized the pH-sensitive and biodegradable amphiphilic polypeptide-based block copolymer methoxy-poly(ethylene glycol)2K-poly(e-caprolactone)4K-poly(glutamic acid)1K (mPEG2K-PCL4K-PGA1K). mPEG2K-PCL4K-PGA1K had low critical aggregation concentration and could self-assemble into polymersomes in aqueous solution revealed by transmission electron microscopy. Therefore, two hydrophilic drug doxorubicin hydrochloride (DOX) and verapamil hydrochloride (VER) were encapsulated into the mPEG2K-PCL4K-PGA1K polymersomes to form poly(DOX + VER) co-delivery system to reverse the multidrug resistance by inhibiting the expression of P-glycoprotein and improve the anti-cancer effect of DOX. The in vitro cytotoxicity experiments indicated the obviously higher inhibition ratio to MCF-7/ADR resistant cells of poly(DOX + VER) compared with that of free DOX solution and polyDOX. The release rate of the two drugs from poly(DOX + VER) were much slower than that from the free drug solutions, and their release behaviors exhibited high pH-sensitive character. Furthermore, the low hemolysis ratio of mPEG2K-PCL4K-PGA1K confirmed that the copolymer could be applied for intravenous injection safely. Therefore, all these findings indicated that the co-delivery of DOX and VER by mPEG2K-PCL4K-PGA1K polymersomes is very promising for cancer therapy.


Journal of Colloid and Interface Science | 2017

Folic acid-grafted bovine serum albumin decorated graphene oxide: An efficient drug carrier for targeted cancer therapy

Naxin Ma; Jing Liu; Wenxiu He; Zhonghao Li; Yuxia Luan; Yunmei Song; Sanjay Garg

Targeting drug carrier systems based on graphene oxide (GO) are of great interest, since it can selectively deliver anticancer drugs to tumor cells, and enhance therapeutic activities with minimized side effects. However, direct grafting target molecules on GO usually results in aggregation of physiological fluid, limiting its biomedical applications. Here, we propose a new strategy to construct targeting GO drug carrier using folic acid grafted bovine serum albumin (FA-BSA) as both the stabilizer and targeting agent. FA-BSA decorated graphene oxide-based nanocomposite (FA-BSA/GO) was fabricated by the physical adsorption of FA-BSA on GO, which was developed as a targeting drug delivery carrier. FA-BSA/GO as the drug carrier was associated with anticancer drug doxorubicin (DOX) through π-π and hydrogen-bond interactions, resulting in high drug loading (up to 437.43μgDOX/mgFA-BSA/GO). FA-BSA/GO/DOX systems demonstrated pH responsive and sustained drug release. The hemolysis ratio of FA-BSA/GO was less than 5%, demonstrating its safety as drug carrier for intravenous injection. Moreover, in vitro cell cytotoxicity and cellular uptake analysis suggested that the constructed FA-BSA/GO/DOX nanohybrids could significantly enhance the anticancer activity. The present work has confirmed the potential for fabrication of highly stable and dispersible GO-based targeting delivery systems for efficient cancer therapy.


Journal of Colloid and Interface Science | 2016

Active targeting co-delivery system based on pH-sensitive methoxy-poly(ethylene glycol)2K-poly(ε-caprolactone)4K-poly(glutamic acid)1K for enhanced cancer therapy

Nuannuan Li; Chunzhi Huang; Yuxia Luan; Yunmei Song; Sanjay Garg

In this paper, we successfully synthesized folate-modified pH-sensitive copolymer methoxy-poly(ethylene glycol)2K-poly(ε-caprolactone)4K-poly(glutamic acid)1K (mPEG2K-PCL4K-PGA1K-FA), which could form the polymeric assembly in an aqueous solution, for co-delivering hydrophilic drugs doxorubicin hydrochloride (DOX) and verapamil hydrochloride (VER) (FA-poly(DOX+VER)). Since VER was an effective P-glycoprotein inhibitor, the combination of DOX and VER could reverse the multidrug resistance efficiently and enhance the therapeutic effect. Therefore, the inhibition ratios of MCF-7/ADR resistant cancer cell treated by FA-poly (DOX+VER) were almost more than 30% higher than those of FA-polyDOX after 48h and 72h. Furthermore, the conjugation of FA could lead the co-delivery systems actively targeting into the FA receptor over-expressing cancer cells in addition to the passive accumulation of the assembly in tumor tissues. Importantly, the prepared mPEG2K-PCL4K-PGA1K-FA assembly showed high pH-sensitive property, which made the drugs mostly released in tumor tissue (acid environment) than in physiological environment (neutral environment). In summary, the as-prepared co-delivery system FA-poly(DOX+VER) demonstrated a high efficiency in reversing the multidrug resistance and targeting FA receptor to improve the anticancer effect of DOX in MCF-7/ADR resistant cells.


Drug Design Development and Therapy | 2015

Development of intramammary delivery systems containing lasalocid for the treatment of bovine mastitis: impact of solubility improvement on safety, efficacy, and milk distribution in dairy cattle

Wen Wang; Yunmei Song; Kiro R. Petrovski; Patricia Eats; Darren J. Trott; Hui San Wong; Stephen W. Page; Jeanette Perry; Sanjay Garg

Background Mastitis is a major disease of dairy cattle. Given the recent emergence of methicillin-resistant Staphylococcus aureus as a cause of bovine mastitis, new intramammary (IMA) treatments are urgently required. Lasalocid, a member of the polyether ionophore class of antimicrobial agents, has not been previously administered to cows by the IMA route and has favorable characteristics for development as a mastitis treatment. This study aimed to develop an IMA drug delivery system (IMDS) of lasalocid for the treatment of bovine mastitis. Methods Minimum inhibitory concentrations (MICs) were determined applying the procedures recommended by the Clinical and Laboratory Standards Institute. Solid dispersions (SDs) of lasalocid were prepared and characterized using differential scanning calorimetry and Fourier transform infrared spectroscopy. IMDSs containing lasalocid of micronized, nano-sized, or as SD form were tested for their IMA safety in cows. Therapeutic efficacy of lasalocid IMDSs was tested in a bovine model involving experimental IMA challenge with the mastitis pathogen Streptococcus uberis. Results Lasalocid demonstrated antimicrobial activity against the major Gram-positive mastitis pathogens including S. aureus (MIC range 0.5–8 μg/mL). The solubility test confirmed limited, ion-strength-dependent water solubility of lasalocid. A kinetic solubility study showed that SDs effectively enhanced water solubility of lasalocid (21–35-fold). Polyvinylpyrrolidone (PVP)-lasalocid SD caused minimum mammary irritation in treated cows and exhibited faster distribution in milk than either nano or microsized lasalocid. IMDSs with PVP-lasalocid SD provided effective treatment with a higher mastitis clinical and microbiological cure rate (66.7%) compared to cloxacillin (62.5%). Conclusion Lasalocid SD IMDS provided high cure rates and effectiveness in treating bovine mastitis with acceptable safety in treated cows.


Journal of Controlled Release | 2016

Development and evaluation of oxaliplatin and irinotecan co-loaded liposomes for enhanced colorectal cancer therapy

Bo Zhang; Tianqi Wang; Shaomei Yang; Yanan Xiao; Yunmei Song; Na Zhang; Sanjay Garg

Drug combinations are widely employed in chemotherapy for colorectal cancer treatment. However, traditional cocktail combination in clinic causes the uncertainty of the treatment, owing to varying pharmacokinetics of different drugs. The aim of this study was to design co-loaded liposomes to achieve the synchronised delivery and release. Oxaliplatin and irinotecan hydrochloride, as one of recommended combination schemes for the treatment of colorectal cancer in clinic, were co-loaded into the liposomes. The particle sizes of the liposomes were <200nm with uniform size distribution. In vitro release study showed that both drugs could be synchronously released from the liposomes, which means the optimized synergistic ratio of two drugs could be achieved. In vitro cellular uptake revealed that co-loaded liposomes could efficiently deliver different drugs into the same cells, indicating their potential as carriers for enhancing the cancer therapy. CLSM images of cryo-sections for in vivo co-delivery study also revealed that co-loaded liposomes had superior ability to co-deliver both the cargoes into the same tumor cells. Besides, in vivo NIRF imaging indicated that the liposomes could increase the drug accumulation in tumor compared with free drug. In vitro cytotoxicity evaluation demonstrated that co-loaded liposomes exhibited higher cytotoxicity than the mixture of single loaded liposomes in both CT-26 and HCT-116 cells. Furthermore, co-loaded liposomes also presented superior anti-tumor activity in CT-26 bearing BALB/c mice. In vivo safety assessment demonstrated that liposomes had lower toxicities than their solution formulations. These results indicated that oxaliplatin and irinotecan hydrochloride co-loaded liposomes would be an efficient formulation for improving colorectal cancer therapy with potential clinical applications.

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Sanjay Garg

University of South Australia

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Ei Mon Phyo Lwin

University of South Australia

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Sean Turner

Boston Children's Hospital

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Cobus Gerber

University of South Australia

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Frank Peddie

University of South Australia

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Catherine Leggett

Boston Children's Hospital

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Usha Ritchie

Boston Children's Hospital

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Allan M. Evans

University of South Australia

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Clive A. Prestidge

University of South Australia

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