Profiling low-mRNA content cells in complex human tissues using BD Rhapsody single-cell analysis.

The successful recovery of immune cells, particularly those with low mRNA content, by single-cell RNA sequencing (scRNA-seq) remains a significant challenge. Tissue dissociation and selection of the appropriate scRNA-seq technology are crucial. Our protocol efficiently recovers low-mRNA content immune cells using the BD Rhapsody scRNA-seq platform.

Design of charge converting lipid nanoparticles via a microfluidic coating technique.

It was the aim of this study to design charge converting lipid nanoparticles (LNP) via a microfluidic mixing technique used for the preparation and coating of LNP. LNP consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, N-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (MPEG-2000-DSPE), and various cationic surfactants were prepared at diverging flow rate ratios (FRR) via microfluidic mixing. Utilizing a second chip in the microfluidic set-up, LNP were coated with polyoxyethylene (9) nonylphenol monophosphate ester (PNPP).

Spray-dried mucoadhesive microparticles based on S-protected thiolated hydroxypropyl-β-cyclodextrin for budesonide nasal delivery.

Budesonide (BUD) is used as first choice therapy for the treatment of allergic rhinitis, a chronic allergic-immune condition with an increased incidence in the pediatric population. The main problem of BUD nasal formulations is related to its poor aqueous solubility (S = 5.03·10 M), sometimes compensated by the administration of high doses of the drug.

Thiolated polymeric hydrogels for biomedical application: Cross-linking mechanisms.

This review focuses on the synthesis of hydrogel networks using thiomers such as thiolated hyaluronic acid, chitosan, cyclodextrin, poly(ethylene glycol) and dextran that are cross-linked via their thiol substructures. Thiomers have been widely investigated as matrix of hydrogels due to the high reactivity of these sulfhydryl moieties. They are well known for their in situ gelling properties due to the formation of inter- and intra-chain disulfide bonds.

Lysine-Based Biodegradable Surfactants: Increasing the Lipophilicity of Insulin by Hydrophobic Ion Paring.

Aim: The aim of this study was to evaluate biodegradable cationic surfactants based on lysine.

Methods: Lysine was esterified with cholesterol, oleyl alcohol and 1-decanol resulting in cholesteryl lysinate (CL), oleyl lysinate (OL) and decyl lysinate (DL). Esters were investigated regarding their log D, critical micelle concentration (CMC) and biodegradability.

Phosphorylated PEG-emulsifier: Powerful tool for development of zeta potential changing self-emulsifying drug delivery systems (SEDDS).

Aim: It was the aim of this study to synthesize a phosphorylated emulsifier possessing a PEG-linker for establishment of a potent zeta potential changing system in self-emulsifying drug delivery systems (SEDDS).

Methods: N,N'-Bis(polyoxyethylene)oleylamine (POA) was phosphorylated utilizing pyrophosphoric acid. Successful synthesis of POA bisphosphate (POAP) was confirmed by NMR and HR CS MAS.

Characterization of an amino acid based biodegradable surfactant facilitating the incorporation of DNA into lipophilic delivery systems.

Hypothesis: Lysine based cationic surfactants are well-tolerated tools for hydrophobic ion pairing (HIP) with DNA and its incorporation into lipophilic delivery systems.

Experiments: Di-Boc-lysine was esterified with 1-hexadecanol and the Boc-residues were cleaved off resulting in hexadecyl lysinate (HL). Subsequently, its Log P and the critical micelle concentration (CMC) were determined.

Self-emulsifying drug delivery systems: In vivo evaluation of their potential for oral vaccination.

Oral Immunization remains a challenge as antigens are rapidly metabolized in the gastrointestinal tract. In numerous previous studies, Self-emulsifying drug delivery systems (SEDDS) have demonstrated to be a promising tool for oral delivery of biologics. In this study, the potential of SEDDS as vehicle for oral vaccination has been evaluated.

Successful development of oral SEDDS: screening of excipients from the industrial point of view.

Oral administration is the most accepted and favored route as various side effects such as fear, pain and risk of infections can be avoided resulting in a comparatively high patient compliance. However, from the industrial point of view the development of oral delivery systems is still challenging as various drugs are poorly soluble as well as slightly permeable leading to low bioavailability. As self-emulsifying drug delivery systems are able to incorporate both hydrophobic and hydrophilic drugs, these carrier systems have received more and more attention within the last years.

In situ gelling and mucoadhesive polymers: why do they need each other?

Introduction: Mucosal drug delivery is an attractive route of administration, particularly in overcoming deficits of conventional dosage forms including high first-pass metabolism and poor bioavailability. Fast drainage from the target mucosa, however, represents a major limitation as it prevents sufficient drug absorption. In order to address these problems, mucoadhesive in situ gelling drug delivery systems have been investigated as they facilitate easy application in combination with a longer residence time at the administration site resulting in more desirable therapeutic effects.

Glyceryl ester surfactants: Promising excipients to enhance the cell permeating properties of SEDDS.

Aim: The aim of the study is the evaluation of the impact of glyceryl ester surfactants on cell permeating properties of SEDDS (self-emulsifying drug delivery systems).

Methods: SEDDS containing the glyceryl ester surfactants polyglyceryl-3-stearate (TGlysurf9), polyglyceryl-5-oleate (TGlysurf11.5) and glyceryl stearate citrate (TGlysurf12) were prepared and characterized regarding droplet size and zeta potential.

ζ potential changing nanoparticles as cystic fibrosis transmembrane conductance regulator gene delivery system: an in vitro evaluation.

Aim: Aim of the study was the development of ζ potential changing nanoparticles as gene delivery system for the cystic fibrosis transmembrane conductance regulator gene.

Methods: Chitosan and carboxymethyl cellulose were modified with phosphotyrosine, a substrate for the brush border enzyme alkaline phosphatase. With these synthesized derivatives, different nanoparticle formulations, including the cystic fibrosis transmembrane conductance regulator gene were prepared by ionic gelation.

Inhibitory effect of emulsifiers in sedds on protease activity: Just an illusion?

Aim: Evaluation of inhibitory effect of emulsifiers on pancreatic trypsin and α-chymotrypsin.

Methods: The inhibitory effect of Cremophor EL, Cremophor RH 40, Brij O10, Tween 20, polyethylene glycol 8000, polyethylene glycol 400, Carbitol, Pemulen TR-1, Pemulen TR-2, Carbopol Ultrez 20 and Carbopol Ultrez 21 on pancreatic trypsin and α-chymotrypsin was tested. BAEE (Nα-Benzoyl-l-arginine ethyl ester), BTEE (N-Benzoyl-l-tyrosine ethyl ester), casein and insulin were used as substrates for trypsin and α-chymotrypsin.

Self-emulsifying drug delivery systems: Design of a novel vaginal delivery system for curcumin.

Aim: The aim of this study was to develop a vaginal self-emulsifying delivery system for curcumin being capable of spreading, of permeating the mucus gel layer and of protecting the drug being incorporated in oily nanodroplets towards mucus interactions and immobilization.

Methods: The emulsifying properties of curcumin loaded SEDDS containing 30% Cremophor RH40, 20% Capmul PG-8, 30% Captex 300, 10% DMSO and 10% tetraglycol (SEDD formulation A) as well as 25% PEG 200, 35% Cremophor RH40, 20% Captex 355, 10% Caprylic acid and 10% Tween 80 (SEDD formulation B) after diluting 1+2 with artificial vaginal fluid were characterized regarding droplet size and zeta potential. Collagen swelling test was used to examine the irritation potential of SEDDS.

Nanoparticular delivery system for a secretoneurin derivative induces angiogenesis in a hind limb ischemia model.

Common therapeutic strategies for peripheral arterial disease often fail to re-establish sufficient blood flow within legs and feet of patients for avoiding critical limb ischemia, what is characterized by a substantial risk for amputation. The neuropeptide secretoneurin induces angiogenesis in models of limb and myocardial ischemia and might be a promising tool in the treatment of patients without the option of revascularization therapy for severe ischemia. Within this manuscript, the biologically active part of secretoneurin was identified, modified by induction of a cysteine residue to gain higher stability against enzymatic degradation and further packed into S-protected thiolated chitosan nanoparticles, which enable intra-muscular application of secretoneurin.

Storage Stability of Bivalirudin: Hydrophilic Versus Lipophilic Solutions.

It was the aim of this study to incorporate a model peptide bivalirudin in self-emulsifying drug delivery system (SEDDS) and compare its storage stability with conventional aqueous solutions. Firstly, bivalirudin lipophilicity was increased via hydrophobic ion pairing using anionic or cationic surfactants. The chosen bivalirudin docusate complex (BIV/AOT) was incorporated into SEDDS composed of 40% (w/w) Cremophor EL, 20% (w/w) Capmul PG-8, and 40% (w/w) propylene glycol with a drug payload of 0.

Development, in vitro and in vivo evaluation of a self-emulsifying drug delivery system (SEDDS) for oral enoxaparin administration.

Aim: The aim of this study was to develop SEDDS for oral enoxaparin administration and evaluate it in vitro and in vivo.

Methods: The emulsifying properties of SEDDS composed of long chain lipids (LC-SEDDS), medium chain lipids (MC-SEDDS), short chain lipids (SC-SEDDS) and no lipids (NL-SEDDS) were evaluated. Thereafter, enoxaparin was incorporated via hydrophobic ion pairing in the chosen SEDDS, which were evaluated regarding their mucus permeating properties, stability towards pancreatic lipase, drug release profile and cytotoxicity.

Thiolated polymers: evaluation of their potential as dermoadhesive excipients.

The objective of this study was to evaluate and compare four different thiolated polymers regarding their dermoadhesive potential. Therefore, three hydrophilic polymers (poly(acrylic acid), Carbopol 971 and carboxymethylcellulose) and a lipophilic polymer (silicone oil) were chosen to generate thiolated polymers followed by characterization. The total work of adhesion (TWA) and the maximum detachment force (MDF) of formulations containing modified and unmodified polymers were investigated on skin obtained from pig ears using a tensile sandwich technique.

Evaluation of the impact of multivalent metal ions on the permeation behavior of Dolutegravir sodium.

Interactions between active pharmaceutical ingredients (APIs) and polyvalent cations are an important factor within drug absorption in the gastrointestinal tract. Dolutegravir sodium, as a second-generation integrase stand transfer inhibitor for the treatment of HIV was investigated regarding chelation with Al(3+), Ca(2+), Fe(3+), Mg(2+ )and Zn(2+) ions at three different molar ratios. Furthermore, the influence of drug-ion chelates on the permeability of the drug across two intestinal membrane models was analyzed.

Mucus permeating thiomer nanoparticles.

The aim of this study was to develop and evaluate a novel mucoadhesive drug delivery system based on thiolated poly(acrylic acid) nanoparticles exhibiting mucolytic properties to enhance particle diffusion into deeper mucus regions before adhesion. Mediated by a carbodiimide, cysteine and the mucolytic enzyme papain were covalently attached to poly(acrylic acid) via amide bond formation. The conjugates were co-precipitated with calcium chloride in order to obtain papain modified (PAA-pap) and thiolated nanoparticles (PAA-cys) as well as particles containing both conjugates (PAA-cys-pap).

Development and evaluation of a novel mucus diffusion test system approved by self-nanoemulsifying drug delivery systems.

The aim of this study was the development of a novel mucus diffusion model and the approval thereof by self-nanoemulsifying drug delivery systems (SNEDDSs). For diffusion experiments, various SNEDD formulations were developed, spiked with fluorescein diacetate, and evaluated for their mucus diffusion behavior through an intestinal mucus layer within the novel setup. In brief, SNEDD formulations resulting in particle sizes of 12.

Preactivated thiomers for vaginal drug delivery vehicles.

It was the purpose of this study to design and evaluate a chitosan derivative as mucoadhesive excipient for vaginal drug delivery systems. The chemical modification of chitosan was achieved by conjugation of thioglycolic acid (TGA) resulting in 1594 μmol thiol groups per gram of polymer followed by the linkage of mercaptonicotinic acid (MNA) to the immobilized thiol groups via disulfide bonding leading to 702 μmol ligand per gram of preactivated polymer. The mucoadhesive properties of these polymers within newly designed vaginal formulations (Chitosan-TGA and Chitosan-TGA-MNA) and commercially available vaginal formulations (Candibene®, Daktarin®, Dalacin®, GynoPevaryl®) were tested over a time period of 24 h via a mucoadhesion test system simulating vaginal conditions, tensile studies and mucus polymer interaction studies via viscosity measurements.

New-generation efflux pump inhibitors.

The development of novel efflux pump inhibitors is an emerging and challenging research field. Besides the use of such excipients in cancer therapy, efflux pump inhibitors are gaining increasing interest with regards to drug delivery. In particular, inhibition of efflux pumps located in the intestine and the blood-brain barrier offers promising prospects.

Thiolated chitosans: useful excipients for oral drug delivery.

To improve the bioavailability of orally administered drugs, formulations based on polymers are of great interest for pharmaceutical technologists. Thiolated chitosans are multifunctional polymers that exhibit improved mucoadhesive, cohesive and permeation-enhancing as well as efflux-pump-inhibitory properties. They can be synthesized by derivatization of the primary amino groups of chitosan with coupling reagents bearing thiol functions.

Polymeric and low molecular mass efflux pump inhibitors for oral drug delivery.

Transmembrane located transporter proteins can be responsible for the low bioavailability of orally administered drugs. Drug delivery systems which can overcome this barrier caused by efflux pumps are therefore highly on demand. Within the current review, intestinal located efflux transporters, methods to identify efflux pump substrates and inhibitors as well as strategies to minimize efflux pump mediated transport of drugs are discussed.