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Over the last few years, among controlled-release delivery systems, multivesicular liposomes (MVLs) have attracted attention due to their unique benefits as a loco-regional drug delivery system. Considering the clinical limitations of the current treatment strategies for osteomyelitis, MVLs can be a suitable carrier for the local delivery of effective antibiotics. This study aimed to prepare vancomycin hydrochloride (VAN HL) loaded MVLs using the active loading method which to the best of our knowledge has not been previously reported. Empty MVLS were prepared by the double emulsion (w/o/w) method and VAN HL was loaded into the prepared liposomes by the ammonium gradient method. After full characterization, the release profile of VAN HL from MVLs was assessed at two different pH values (5.5 and 7.4), and compared with the release profile of the free drug and also passively loaded MVLs. In vitro antimicrobial activities were evaluated using the disc diffusion method. Our results demonstrated that the encapsulation efficiency was higher than 90% in the optimum actively loaded MVL. The free VAN HL was released within 6-8 h, while the passively loaded MVLs and the optimum actively loaded MVL formulation released the drug in 6 days and up to 19 days, respectively. The released drug showed effective antibacterial activity against osteomyelitis-causing pathogens. In conclusion, the prepared formulation offered the advantages of sustained-release properties, appropriate particle size as well as being composed of biocompatible materials, and thus could be a promising candidate for the loco-regional delivery of VAN HL and the management of osteomyelitis.

Saideh Fakharzadeh,1,2 Hassan Argani,1 Simin Dadashzadeh,3 Somayeh Kalanaky,2 Peyman Mohammadi Torbati,4 Mohammad Hassan Nazaran,2 Abbas Basiri5 1Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 3Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Department of Pathology, Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Urology and Nephrology Research Center, Shahid Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IranCorrespondence: Mohammad Hassan NazaranDepartment of Research and Development, Sodour Ahrar Shargh Company, Tehran, IranTel/ Fax +98 21 88992123Email mnazaran@nanochelatingtechnology.comAbbas BasiriUrology and Nephrology Research Center, Shahid Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IranTel/ Fax +98 21 22567222Email basiri@unrc.irBackground: One common feature of chronic diseases, such as cancer, diabetes and chronic kidney disease (CKD), is the disruption of iron metabolism and increase in labile iron pool, which can result in excessive production of harmful oxidative stress. The proper management of iron metabolism in this situation can be a valuable tool to ameliorate pathological events.Materials and Methods: In the previous studies, the anti-neoplastic effects of BCc1, a nanochelating-based nanomedicine with iron-chelating property, were demonstrated in cell culture, animal models and clinical trials. In the present study, the therapeutic effects of BCc1 in animal model of diabetic kidney disease (DKD), induced by streptozotocin injection (35 mg/kg) and high-fat diet consumption, were evaluated.Results: The results showed that BCc1 significantly decreased HOMA-IR index, uric acid, blood urea nitrogen, malondialdehyde and 8-isoprostane. In addition, it reduced urinary albumin excretion rate and albumin-to-creatinine ratio in comparison to DKD control rats. This nanomedicine had no negative impact on liver iron content, hemoglobin level, red blood cell count, hematocrit and mean corpuscular volume, while it significantly decreased aspartate aminotransferase and alanine aminotransferase compared to DKD control group. Moreover, the histopathological assessment indicated that lesser glomerular basement membrane and wrinkling, mesangial matrix expansion and pathological changes in proximal cortical tubules were seen in the kidney samples of BCc1-treated rats.Conclusion: In conclusion, BCc1 as an iron-chelating agent shows promising impacts in DKD animal model, which can ameliorate biochemical and pathological events of this disease.Keywords: BCc1, diabetic kidney disease, chronic kidney disease, nanochelating technology, iron

Morteza Yaghoobian,1 Azadeh Haeri,1 Noushin Bolourchian,1 Soraya Shahhosseni,2 Simin Dadashzadeh1,3 1Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranCorrespondence: Simin DadashzadehDepartment of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran 14155-6153, IranTel +98 21 88200070Fax + 98 21 88209620Email Sdadashzadeh@sbmu.ac.irBackground: Niosomes, bilayer vesicles formed by the self-assembly of nonionic surfactants, are receiving increasing attention as potential oral drug delivery systems but the impact of niosomal formulation parameters on their oral capability has not been studied systematically. The aim of this study was to investigate the impact of surfactant composition and surface charge of niosomes in enhancing oral bioavailability of repaglinide (REG) as a BCS II model drug.Methods: Niosomes (13 formulations) from various nonionic surfactants having HLB in the range of 4– 28 (Tweens, Spans, Brijs, Myrj, poloxamer 188, TPGS and Labrasol) were prepared and characterized concerning their loading efficiency, hydrodynamic diameter, zeta potential, drug release profile, and stability. The oral pharmacokinetics of the selected formulations were studied in rats (8 in vivo groups).Results: The results revealed that type of surfactant markedly affected the in vitro and in vivo potentials of niosomes. The Cmax and AUC values of REG after administration of the selected niosomes as well as the drug suspension (as control) were in the order of Tween 80> TPGS> Myrj 52> Brij 35> Span 60≈Suspension. Adding stearyl amine as a positive charge-inducing agent to the Tween 80-based niosomes, resulted in an additional increase in drug absorption and values of AUC and Cmax were 3.8- and 4.7-fold higher than the drug suspension, respectively.Conclusion: Cationic Tween 80-based niosomes may represent a promising platform to develop oral delivery systems for BCS II drugs.Keywords: repaglinide, niosome, oral bioavailability, surfactant type, surface charge, BCS II, HLB