Search

Mohammad Arafat,1 Yunmei Song,1 Kyle Brewer,2 Paris Fouladian,1 Ankit Parikh,1 Hugo Albrecht,3 Anton Blencowe,2 Sanjay Garg1 1Pharmaceutical Innovation and Development (PIDG) Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia; 2Applied Chemistry and Translational Biomaterials (ACTB) Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia; 3Drug Discovery and Development Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, AustraliaCorrespondence: Sanjay GargPharmaceutical Innovation and Development (PIDG) Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, AustraliaEmail Sanjay.Garg@unisa.edu.auAnton BlencoweApplied Chemistry and Translational Biomaterials (ACTB) Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, AustraliaEmail Anton.Blencowe@unisa.edu.auBackground: Drug-eluting gastrointestinal (GI) stents are emerging as promising platforms for the treatment of GI cancers and provide the combined advantages of mechanical support to prevent lumen occlusion and as a reservoir for localized drug delivery to tumors. Therefore, in this work we present a detailed quality assurance study of 5-fluorouracil (5FU) drug-eluting stents (DESs) as potential candidates for the treatment of obstructive GI cancers.Methods: The 5FU DESs were fabricated via a simple two-step sequential dip-coating process of commercial GI self-expanding nitinol stents with a 5FU-loaded polyurethane basecoat and a drug-free protective poly(ethylene-co-vinyl acetate) topcoat. The drug loading, content uniformity and drug stability were determined using a validated high-performance liquid chromatography (HPLC) method, which is also recommended in the United States Pharmacopeia. In vitro drug release studies were performed in phosphate buffered saline to determine the drug releasing properties of the two 5FU-l

Wei Zhang,1 Yunmei Song,1 Preethi Eldi,1 Xiuli Guo,2 John D Hayball,1,3 Sanjay Garg,1 Hugo Albrecht1 1Centre for Pharmaceutical Innovation and Development, Centre for Drug Discovery and Development, Experimental Therapeutics Laboratory, Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia; 2Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, China; 3Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia Abstract: Prostate cancer cells frequently overexpress the gastrin-releasing peptide receptor, and various strategies have been applied in preclinical settings to target this receptor for the specific delivery of anticancer compounds. Recently, elastin-like polypeptide (ELP)-based self-assembling micelles with tethered GRP on the surface have been suggested to actively target prostate cancer cells. Poorly soluble chemotherapeutics such as docetaxel (DTX) can be loaded into the hydrophobic cores of ELP micelles, but only limited drug retention times have been achieved. Herein, we report the generation of hybrid ELP/liposome nanoparticles which self-assembled rapidly in response to temperature change, encapsulated DTX at high concentrations with slow release, displayed the GRP ligand on the surface, and specifically bound to GRP receptor expressing PC-3 cells as demonstrated by flow cytometry. This novel type of drug nanocarrier was successfully used to reduce cell viability of prostate cancer cells in vitro through the specific delivery of DTX. Keywords: ELP-GRP, micelle, liposome, docetaxel, prostate cancer, GRPR, GPCR

Ei Mon Phyo Lwin,1 Catherine Leggett,2 Usha Ritchie,2 Cobus Gerber,1 Yunmei Song,1 William Hague,3,4 Sean Turner,2 Richard Upton,1 Sanjay Garg11School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia; 2SA Pharmacy, Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia; 3Robinson Research Institute, University of Adelaide, SA 5006, Australia; 4Obstetric Medicine, Women’s and Children’s Hospital, North Adelaide, SA 5006, AustraliaIntroduction: Rosuvastatin reduces concentrations of total cholesterol (TC) and is used for the management of hypercholesterolemia and prevention of acute coronary syndromes. There are no published reports estimating infant exposure to rosuvastatin through breast milk.Purpose: The aims of this study were to quantify concentrations of rosuvastatin in human milk and plasma from a lactating woman taking rosuvastatin and to investigate potential infant exposure.Materials and methods: A 38-year-old breastfeeding mother was commenced on rosuvastatin 20 mg daily for secondary prevention of an acute coronary syndrome. Eight maternal breast milk samples and a single plasma sample were collected over a 24-hour period. The samples were quantified using a sensitive liquid chromatography–mass spectrometry (LC-MS/MS) method.Results: The average concentration of rosuvastatin in breast milk was 30.84 ng/mL, and a peak concentration of 58.59 ng/mL occurred at 17 hours after oral administration. Although the milk-to-plasma (M/P) ratio was 16.49 at 14 hours, the theoretical infant dosage (TID) and relative infant dose (RID) were 0.005 mg/kg/day and 1.50%, respectively.Conclusion: The findings suggest that only small amounts of rosuvastatin pass into breast milk. Should the maternal condition necessitate treatment, consideration could be given to the use of rosuvastatin during breastfeeding provided the infant is monitored.Keywords: rosuvastatin, LC-MS/MS

Bo Zhang,1 Yunmei Song,2 Tianqi Wang,1 Shaomei Yang,1 Jing Zhang,1 Yongjun Liu,1 Na Zhang,1 Sanjay Garg2 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong Province, People’s Republic of China; 2Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Abstract: Combinational nanomedicine is becoming a topic of much interest in cancer therapy, although its translation into the clinic remains extremely challenging. One of the main obstacles lies in the difficulty to efficiently co-deliver immiscible hydrophilic/hydrophobic drugs into tumor sites. The aim of this study was to develop co-loaded lipid emulsions (LEs) to co-deliver immiscible hydrophilic/hydrophobic drugs to improve cancer therapy and to explore the co-delivery abilities between co-loaded LEs and mixture formulation. Multiple oxaliplatin/irinotecan drug–phospholipid complexes (DPCs) were formulated. Co-loaded LEs were prepared using DPC technique to efficiently encapsulate both drugs. Co-loaded LEs exhibited uniform particle size distribution, desired stability and synchronous release profiles in both drugs. Co-loaded LEs demonstrated superior anti-tumor activity compared with the simple solution mixture and the mixture of single-loaded LEs. Furthermore, co-loaded nanocarriers could co-deliver both drugs into the same cells more efficiently and exhibited the optimized synergistic effect. These results indicate that co-loaded LEs could be a desired formulation for enhanced cancer therapy with potential application prospects. The comparison between co-loaded LEs and mixture formulation is significant for pharmaceutical designs aimed at co-delivery of multiple drugs. Keywords: cancer, combination therapy, co-delivery, lipid emulsions, drug–phospholipid complex

Wen Wang,1 Yunmei Song,1 Kiro Petrovski,2 Patricia Eats,2 Darren J Trott,2 Hui San Wong,2 Stephen W Page,3 Jeanette Perry,2 Sanjay Garg11School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA, Australia; 2School of Animal and Veterinary Sciences, University of Adelaide, Adelaide, SA, Australia; 3Luoda Pharma Pty Ltd, Caringbah, NSW, AustraliaBackground: 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 distri