In situ Formation of Polymer Microparticles in Bacterial Nanocellulose Using Alternative and Sustainable Solvents to Incorporate Lipophilic Drugs.

Bacterial nanocellulose has been widely investigated in drug delivery, but the incorporation of lipophilic drugs and controlling release kinetics still remain a challenge. The inclusion of polymer particles to encapsulate drugs could address both problems but is reported sparely. In the present study, a formulation approach based on in situ precipitation of poly(lactic-co-glycolic acid) within bacterial nanocellulose was developed using and comparing the conventional solvent -methyl-2-pyrrolidone and the alternative solvents poly(ethylene glycol), Cyrene and ethyl lactate.

Encapsulation of the Anti-inflammatory Dual FLAP/sEH Inhibitor Diflapolin Improves the Efficiency in Human Whole Blood.

Diflapolin is a dual FLAP/sEH inhibitor with potent anti-inflammatory efficiency in cellular assays and experimental in vivo studies. Despite these outstanding characteristics, its high lipophilicity and plasma protein binding hamper the bioactivity in blood. To overcome these limitations, diflapolin was encapsulated in poly(lactic-co-glycolic acid) nanoparticles to develop an efficient and biocompatible drug delivery system.

Sustainable preparation of anti-inflammatory atorvastatin PLGA nanoparticles.

In the present study, the anti-inflammatory lipophilic drug atorvastatin was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) using a sustainable method in comparison to the standard emulsion-diffusion-evaporation technique. For the sustainable method the organic solvent ethyl acetate was fully replaced by 400 g/mol poly(ethylene glycol) (PEG 400). Both techniques led to the formation of nanoparticles with comparable sizes of about 170 to 247 nm depending on the polymer type, with monomodal size distribution and negative zeta potential.

Cyrene™ as an Alternative Sustainable Solvent for the Preparation of Poly(lactic-co-glycolic acid) Nanoparticles.

Toxic and environmental harmful organic solvents are widely applied to prepare poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NP) in standard preparation methods. Alternative non-toxic solvents suffer from disadvantages like high viscosity and plasticizing effects. To overcome these hurdles, Cyrene™ as a new sustainable, non-toxic and low viscous solvent was used to formulate PLGA NPs.

Overcoming the hydrophilicity of bacterial nanocellulose: Incorporation of the lipophilic coenzyme Q10 using lipid nanocarriers for dermal applications.

Although used in a wide range of medical and pharmaceutical applications, the potential of the natural biopolymer bacterial nanocellulose (BNC) as drug delivery system is by far not fully exploited. Particularly, the incorporation of lipophilic drugs is still considered as an unsolved task. In the present study, the homogeneous incorporation of the lipophilic coenzyme Q10 (CoQ10) into BNC was accomplished by several post-synthesis techniques utilizing different nanoemulsions and liposomes.

Development and characterization of bacterial nanocellulose loaded with Boswellia serrata extract containing nanoemulsions as natural dressing for skin diseases.

The combination of the anti-inflammatory lipophilic Boswellia serrata extract with the natural hydropolymer bacterial nanocellulose (BNC) for the treatment of skin diseases is counteracted by their different hydro/lipophilicity. To overcome the hydrophilicity of the BNC, the water in its network was exchanged by single and double nanoemulsions. Incorporation of the Boswellia serrata extract in the nanoemulsions formed particles of about 115 to 150 nm with negative zeta potential and storage stability over 30 days at temperatures between 4 and 32 °C.

Process control and scale-up of modified bacterial cellulose production for tailor-made anti-inflammatory drug delivery systems.

Bacterial cellulose (BC) has proven its high potential as active wound dressing and drug delivery system in many scientific studies, but the transferability of the methods to efficient manufacturing still needs to be demonstrated. This study presents a technically feasible, straightforward and efficient approach to modify BC according to specific medical requirements, to scale-up the cultivation and to load the active pharmaceutical ingredient of interest. By means of in situ-modification of the network structure using water-soluble poly(ethylene glycol) 400 and 4000 on pilot-scale, up to 41.

Simulation of the long-term fate of superparamagnetic iron oxide-based nanoparticles using simulated biological fluids.

To simulate the stability and degradation of superparamagnetic iron oxide nanoparticles (MNP) as part of their life cycle using complex simulated biological fluids. A set of 13 MNP with different polymeric or inorganic shell materials was synthesized and characterized regarding stability and degradation of core and shell in simulated biological fluids. All MNP formulations showed excellent stability during storage and in simulated body fluid.

Tailor-made material characteristics of bacterial cellulose for drug delivery applications in dentistry.

Bacterial cellulose (BC) has shown high potential as innovative wound dressing and drug delivery system. Bringing both together, drug-loaded BC was investigated for applications in dental therapies such as dental extraction or mucosal transplantation. Both applications would benefit from a material which degrades under physiological conditions, and from an antibiotic environment.

Polyester-based particles to overcome the obstacles of mucus and biofilms in the lung for tobramycin application under static and dynamic fluidic conditions.

Pulmonary infections with Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) are difficult to treat and related with high mortality in some diseases like cystic fibrosis due to the recurrent formation of biofilms. The biofilm formation hinders efficient treatment with inhaled antibiotics due to a low penetration of the antibiotics through the polyanionic biofilm matrix and increased antimicrobial resistance of the biofilm-embedded bacteria. In this study, tobramycin (Tb) was encapsulated in particles based on poly(d,l,-lactide-co-glycolide) (PLGA) and poly(ethylene glycol)-co-poly(d,l,-lactide-co-glycolide) diblock (PEG-PLGA) to overcome the biofilm barrier with particle sizes of 225-231 nm (nanoparticles) and 896-902 nm (microparticles), spherical shape and negative zeta potentials.

Study on the in situ aggregation of liposomes with negatively charged phospholipids for use as injectable depot formulation.

Compared to conventional parenteral formulations injectable depot formulations, owing to a sustained drug release, offer several advantages, such as a reduced dosing frequency - and consequent improved compliance - or a predictable release profile. Additionally, fluctuations in the drug blood level may be smoothened and consequently side effects reduced. Because of their capability to encapsulate water soluble drugs and their very low toxicity profile liposomes comprising phospholipids, most certainly represent a vehicle of choice for subcutaneous (s.

Structural Characterization of Self-Assembling Hybrid Nanoparticles for Bisphosphonate Delivery in Tumors.

Hybrid self-assembling nanoparticles (hsaNPs) encapsulating bisphosphonates (BPs) recently showed very promising results in preclinic experiments for the treatment of brain tumor. However, the poor knowledge on the architecture of hybrid nanovectors is certainly one of the main reasons hampering further clinical and industrial development of these technologies. Here we propose to combine different techniques, that is, small angle neutron scattering (SANS) and X-ray Sscattering (SAXS), with cryo-electron transmission microscopy (cryo-TEM) to study the architecture of the final hsaNPs as well as of the four components before the assembling process.

Preparation of PEGylated liposomes incorporating lipophilic lomeguatrib derivatives for the sensitization of chemo-resistant gliomas.

Liposomal delivery is a well-established approach to increase the therapeutic index of drugs, mainly in the field of cancer chemotherapy. Here, we report the preparation and characterization of a new liposomal formulation of a derivative of lomeguatrib, a potent O-methylguanine-DNA methyltransferase (MGMT) inactivator. The drug had been tested in clinical trials to revert chemoresistance, but was associated with a low therapeutic index.

Micro-spherical cochleate composites: method development for monodispersed cochleate system.

Cochleates have been of increasing interest in pharmaceutical research due to their extraordinary stability. However the existing techniques used in the production of cochleates still need significant improvements to achieve sufficiently monodispersed formulations. In this study, we report a simple method for the production of spherical composite microparticles (3-5 μm in diameter) made up of nanocochleates from phosphatidylserine and calcium (as binding agent).

Understanding cochleate formation: insights into structural development.

Understanding the structure and the self-assembly process of cochleates has become increasingly necessary considering the advances of this drug delivery system towards the pharmaceutical industry. It is well known that the addition of cations like calcium to a dispersion of anionic lipids such as phosphatidylserines results in stable, multilamellar cochleates through a spontaneous assembly. In the current investigation we have studied the intermediate structures generated during this self-assembly of cochleates.

Electron microscopy and theoretical modeling of cochleates.

Cochleates are self-assembled cylindrical condensates that consist of large rolled-up lipid bilayer sheets and represent a novel platform for oral and systemic delivery of therapeutically active medicinal agents. With few preceding investigations, the physical basis of cochleate formation has remained largely unexplored. We address the structure and stability of cochleates in a combined experimental/theoretical approach.

Lipid colloidal carriers for improvement of anticancer activity of orally delivered quercetin: formulation, characterization and establishing in vitro-in vivo advantage.

Novel lipid nanocarriers, GeluPearl (GP) comprising of Precirol ATO 5 lipid nanoparticles with (GPNLC) or without oil (GPSLN), loaded with Quercetin (QR), were successfully fabricated to improve therapeutic efficacy. QR loaded GP nanoparticles were optimized to yield adequate colloidal stability, mean particle size in range of 350-380 nm and entrapment efficiency of more than 90%. GPSLN and GPNLC were characterized for morphological evaluation by virtue of cryo-TEM, surface charge, protection offered to QR against alkali mediated degradation and fluorescence studies to evaluate QR-lipid interaction.

Lecithin-based novel cationic nanocarriers (LeciPlex) I: fabrication, characterization and evaluation.

Aims: In the present investigation, the feasibility of fabricating novel self-assembled cationic nanocarriers (LeciPlex) containing cetyltrimethylammonium bromide (CTAB) or didodecyldimethylammonium bromide (DDAB) and soybean lecithin using pharmaceutically acceptable biocompatible solvents such as 2-Pyrrolidone (Soluphor P) and diethyleneglycol monoethyl ether (Transcutol) was established.

Materials & Methods: The interaction between DDAB/CTAB and soybean lecithin in the nanocarriers was confirmed by differential scanning calorimetry and in vitro antimicrobial studies. The positive charge on the nanocarriers was confirmed by zeta potential analysis.

Lecithin-based novel cationic nanocarriers (Leciplex) II: improving therapeutic efficacy of quercetin on oral administration.

The objective of the present investigation was to evaluate ability of the novel self-assembled phospholipid- based cationic nanocarriers (LeciPlex) in improving the therapeutic efficacy of a poorly water-soluble natural polyphenolic agent, quercetin (QR), on oral administration. Quercetin loaded LeciPlex (QR-LeciPlex) were successfully fabricated using a biocompatible solvent Transcutol HP. The QR-LeciPlex were characterized for particle size, encapsulation efficiency, zeta potential, and particle morphology by cryo-TEM.