Increase In Loading Efficiency Research Articles

Microfluidic Synthesis of Rifampicin Loaded PLGA Nanoparticles and the Effect of Formulation on their Physical and Antibacterial Properties

The encapsulation of drugs in nanoparticles serves as an effective way to modify pharmacokinetics and therapeutic efficacy. Nanoparticles comprised of poly(d,l-lactide-co-glycolide) (PLGA) are well suited for this purpose; they are accessible using multiple synthesis methods, are highly biocompatible and biodegradable, and possess desirable drug release properties. In the present study, we have explored the effects of various formulation parameters on the physical properties of PLGA nanoparticles synthesised using a microfluidic assisted nanoprecipitation method and loaded with a model drug. PLGA nanoparticles, with diameters ranging from 165–364nm, were produced using three alternate stabilisers; poly(vinyl alcohol) (PVA), d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), and didodecyldimethylammonium bromide (DMAB). Three additional formulations used PVA in addition to 20wt-% 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA), and oleic acid. Spectrophotometric analysis demonstrated that the use of PVA increased the loading efficiency over that of TPGS and DMAB formulations, while the inclusion of oleic acid in the PVA formulation resulted in a further 3-fold increase in loading efficiency. Invitro release studies demonstrate that the inclusion of lipid additives significantly alters release kinetics; release was most rapid and complete in the formulation containing oleic acid, while the addition of DOTAP and DOTMA significantly reduced release rates. Finally, the antimicrobial activity of each formulation was tested against Staphylococcus aureus and Bacillus cereus, with minimum inhibitory concentrations nearing or exceeding that of free rifampicin.

Enhanced Intraliposomal Metallic Nanoparticle Payload Capacity Using Microfluidic-Assisted Self-Assembly

Hybrids composed of liposomes (L) and metallic nanoparticles (NPs) hold great potential for imaging and drug delivery purposes. However, the efficient incorporation of metallic NPs into liposomes using conventional methodologies has so far proved to be challenging. In this study, we report the fabrication of hybrids of liposomes and hydrophobic gold NPs of size 2-4 nm (Au) using a microfluidic-assisted self-assembly process. The incorporation of increasing amounts of AuNPs into liposomes was examined using microfluidics and compared to L-AuNP hybrids prepared by the reverse-phase evaporation method. Our microfluidics strategy produced L-AuNP hybrids with a homogeneous size distribution, a smaller polydispersity index, and a threefold increase in loading efficiency when compared to those hybrids prepared using the reverse-phase method of production. Quantification of the loading efficiency was determined by ultraviolet spectroscopy, inductively coupled plasma mass spectroscopy, and centrifugal field flow fractionation, and qualitative validation was confirmed by transmission electron microscopy. The higher loading of gold NPs into the liposomes achieved using microfluidics produced a slightly thicker and more rigid bilayer as determined with small-angle neutron scattering. These observations were confirmed using fluorescent anisotropy and atomic force microscopy. Structural characterization of the liposomal-NP hybrids with cryo-electron microscopy revealed the coexistence of membrane-embedded and interdigitated NP-rich domains, suggesting AuNP incorporation through hydrophobic interactions. The microfluidic technique that we describe in this study allows for the automated production of monodisperse liposomal-NP hybrids with high loading capacity, highlighting the utility of microfluidics to improve the payload of metallic NPs within liposomes, thereby enhancing their application for imaging and drug delivery.

Lipid model membranes for drug interaction study

The present work shows a structural study on the process of incorporation of a hydrophobic drug, Ellipticine (ELPT), into lipid model membranes for drug targeting purpose. The ELPT is an alkaloid that showed an anti-proliferation activity against several types of tumor cells and against the HIV1 virus. We used the zwitterionic lipid dipalmitoyl phosphatidylcholine (DPPC) and four different anionic lipids: cardiolipin (CL), dipalmitoyl phosphatidic acid (DPPA), dipalmitoyl phosphatidylglycerol (DPPG) and dipalmitoyl phosphatidylserine (DPPS), both spread on a Langmuir monolayer and deposited on a solid substrate to mimic a model membrane and study the interaction with the drug ELPT. X-ray reflectivity results pointed toward an increase in drug loading efficiency up to 13.5% mol/mol of ELPT into mixed systems DPPC/CL. This increase in loading efficiency was also accompanied by a slight distortion in the stacking of the bilayers less evidenced after optimization of the molar ratio between the co-lipids. Grazing incidence X-ray diffraction measurements revealed an in-plane lattice distortion due to the presence of hydrocarbon chain backbone ordering in pure systems of DPPC doped with ELPT. The same was not observed in mixed membranes with DPPC/CL and DPPC/DPPA.

Lipid model membranes for drug interaction study

The present work shows a structural study on the process of incorporation of a hydrophobic drug, Ellipticine (ELPT), into lipid model membranes for drug targeting purpose. The ELPT is an alkaloid that showed an anti-proliferation activity against several types of tumor cells and against the HIV1 virus. We used the zwitterionic lipid dipalmitoyl phosphatidylcholine (DPPC) and four different anionic lipids: cardiolipin (CL), dipalmitoyl phosphatidic acid (DPPA), dipalmitoyl phosphatidylglycerol (DPPG) and dipalmitoyl phosphatidylserine (DPPS), both spread on a Langmuir monolayer and deposited on a solid substrate to mimic a model membrane and study the interaction with the drug ELPT. X-ray reflectivity results pointed toward an increase in drug loading efficiency up to 13.5% mol/mol of ELPT into mixed systems DPPC/CL. This increase in loading efficiency was also accompanied by a slight distortion in the stacking of the bilayers less evidenced after optimization of the molar ratio between the co-lipids. Grazing incidence X-ray diffraction measurements revealed an in-plane lattice distortion due to the presence of hydrocarbon chain backbone ordering in pure systems of DPPC doped with ELPT. The same was not observed in mixed membranes with DPPC/CL and DPPC/DPPA.

Increase of Liposome Stability by Incorporation of Bovine Serum Albumin

AbstractThe incorporation of the bovine serum albumin in the liposomal membrane to prevent leakage of the entrapped contents was studied. Adsorption of bovine serum albumin was found on the liposomes. After the adsorption of bovine serum albumin, by the addition of glutaraldehyde, the serum albumin molecules cross-linked to themselves and stiffened the membrane structure of the liposomes. It was found that the particle size of the liposomes increased after the treatment of glutaraldehyde. However, there was no significant change in particle size for the liposomes with the stirring effect. Adriamycin, methotrexate, carboxyfluorescein and mitoxantrone were entrapped into this liposome system. The loading efficiency demonstrated a similar value for the liposomes with and without the treatment of glutaraldehyde. However, for the entrapment of adriamycin, there showed an increase in loading efficiency with the effect of glutaraldehyde. For the leakage examination, a decrease of the release rate of the adriamyc...