Search

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.

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

The present study was conducted to investigate the performance of different size reduction techniques including probe sonication, extrusion, and high pressure homogenization for nanosizing of niosomes. Also, the effects of cholesterol content and surfactant type on the size and poly dispersity index (PDI) of the formulations were evaluated. Various niosomal formulations composed of Brij 72, Span 60, or Tween 60 were prepared and then, to reduce vesicle size and minimize the PDI, the niosomes were treated by various post-processing procedures. Surfactant type showed a significant effect on the particle size of the niosomes. The particle size of Tween 60 niosomes was significantly larger than those of Span 60 and Brij 72 niosomes (P < 0.05), indicating that at the same cholesterol content, niosomes composed of a surfactant with a higher HLB value show larger particle size than those with a lower HLB value. The influences of cholesterol content as well as downsizing methods, on the particle size and distribution of niosomes were significantly dependent on the surfactant composition of the niosomes. Extrusion and probe sonication were found to be the most efficient methods for size reduction of the Tween 60 and Span 60 niosomes, while for downsizing of Brij 72 niosomes, all employed methods were efficient and resulted in the approximately similar size of about 200 nm. In conclusion, the selection of an efficient method for nanosizing of niosomes and also achievement of a desired size range, and homogeneity highly depends on the niosome composition, particularly on the employed surfactant type.

The aim of current study was to investigate the effect of Brij decoration of liposomes on in-vitro and in-vivo characteristics of the nanocarriers. Two hydrophilic Brij surfactants (Brij 35 and Brij 78) with almost similar molecular weight but differing in acyl chain were incorporated into liposomal bilayers at two percentages (5% and 10%). Conventional liposomes (CL) containing egg phosphatidylcholine and cholesterol as well as Brij-enriched liposomal dispersions were prepared and characterized. In-vivo pharmacokinetics of various liposomal formulations and drug solution (six groups) was studied after intravenous administration to rats. Conventional and Brij enriched doxorubicin (DOX) liposomes had small size within 82-97 nm and showed homogenous distribution (PDI < 0.1). Drug encapsulation was higher than 97% in all liposomes. The drug release profiles proved sustained DOX release from various formulations. Based on the results of in-vivo studies, all five liposomes increased drug exposure and plasma concentration in comparison to free drug. However, DOX liposomes enriched with 5% of either Brij 35 or Brij 78 showed higher AUC values and lower clearance. Overall, Brij surfactants (5% of bilayer lipids) could be potentially used to improve liposomal pharmacokinetic parameters.

Specific delivery of therapeutic agents to solid tumors and their bioavailability at the target site are the most clinically important and challenging goals in cancer therapy. Liposomes are promising nanocarriers and have been well investigated for cancer therapy. In spite of preferred accumulation in tumors via the enhanced permeability and retention (EPR) effect, inefficient drug release at the target site and endosomal entrapment of long circulating liposomes are very important obstacles for achieving maximum anticancer efficacy. Thus, additional strategies such as stimulus-sensitive drug release are necessary to improve efficacy. Stimuli-sensitive liposomes are stable in blood circulation, however, activated by responding to external or internal stimuli and control the cargo release at the target site. This review focuses on state of the art of stimuli-responsive liposomes. Both external stimuli-responsive liposomes, including hyperthermia (HT), magnetic, light, and ultrasound-sensitive liposomes and internal stimuli (pH, reduction, and enzyme) responsive liposomes are covered.

Restenosis is one of the major complications affecting outcomes of percutaneous coronary interventions. The aims of this study were to formulate curcumin (CUR) nanoparticles by using only lipidic ingredients in the absence of any organic solvent and to determine key formulation parameters using 2-level factorial design. CUR nanoparticles were prepared using triglyceride and egg phosphatidylcholine (EPC) by high-pressure homogenization (HPH) and fully characterized regarding drug loading, particle size, zeta potential, stability, drug release profile, conductivity, viscosity, refractive index, stability, morphology and FTIR analysis. The efficacy of CUR nanoparticles in inhibiting restenosis was investigated in a rat carotid artery model. Balloon-injured rats were randomly assigned to two control (saline and empty carrier) groups and CUR nanoparticle treated group. Arterial restenosis was assessed by histomorphometric, immunohistochemical and CT angiography analyses. Optimized CUR nanoparticles with almost 70% drug entrapment, an average particle size of 58 nm, PDI