Matthias Gerhard Wacker

Matthias Gerhard Wacker
National University of Singapore | NUS · Department of Pharmacy

PhD

About

84
Publications
12,758
Reads
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1,437
Citations
Citations since 2017
59 Research Items
1095 Citations
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Introduction
Our lab specializes in the development of in vitro performance assays for injectables and perorally applied dosage forms. We utilize biopredictive in vitro release assays and physiologically-based biopharmaceutics modelling to explain and predict the in vivo behavior of long-acting depot formulations, liposomal delivery systems and peroral dispersions. Read more on our website www.nanomedicines.de
Additional affiliations
April 2013 - February 2019
Fraunhofer Institute for Molecular Biology and Applied Ecology IME
Position
  • Department head
December 2010 - January 2019
Goethe-Universität Frankfurt am Main
Position
  • Senior Researcher
Description
  • Lectures in Pharmaceutical Technology and Biopharmacy and guest lectures at the State University of Maringá (Brazil) and the University of Namibia

Publications

Publications (84)
Preprint
Malaria is a vector-borne parasitic disease that affects millions worldwide. In order to reach the objective, set by the World Health Organization to decrease the cases by 2030, antimalarial drugs with novel modes of action are required. Previously, a novel mechanism of action of chloroquine (CQ) was reported involving features of programmed cell d...
Article
Background: Chronic wounds often contain high levels of proinflammatory cytokines that prolong the wound-healing process. Patients suffering from these conditions are likely to benefit from topical rifampicin therapy. Although recent research indicates considerable anti-inflammatory properties of the antibiotic, currently, there are no commercial...
Article
Topical preparations of hydrocortisone can be used for the anti-inflammatory treatment of the female genital area. Although the drug is a low-strength corticosteroid, systemic absorption and distribution of the drug are the most common safety risks associated with this therapy. In the current investigation, we elucidate the physicochemical properti...
Article
Full-text available
The subset of plasma extracellular vesicles (EVs) that coprecipitate with low-density lipoprotein (LDL-EVs) carry coagulation and fibrinolysis pathway proteins as cargo. We investigated the association between LDL-EV hemostatic/fibrinolysis protein ratios and post-acute myocardial infarction (post-AMI) left ventricular (LV) remodeling which precede...
Article
Full-text available
Chronic wounds exhibit elevated levels of inflammatory cytokines, resulting in the release of proteolytic enzymes which delay wound-healing processes. In recent years, rifampicin has gained significant attention in the treatment of chronic wounds due to an interesting combination of antibacterial and anti-inflammatory effects. Unfortunately, rifamp...
Article
At present, tricaprilin is used as a ketogenic source for the management of mild to moderate Alzheimer’s disease. After administration of the medium-chain triglyceride, tricaprilin is hydrolyzed to octanoic acid and further metabolized to ketones, acting as an alternative energy substrate for the brain. In this investigation, we developed a physiol...
Article
Full-text available
Extracellular vesicles (EVs) represent a diverse class of lipid bilayer membrane vesicles released by both animal and plant cells. These ubiquitous vesicles are involved in intercellular communication and transport of various biological cargos, including proteins, lipids, and nucleic acids. In recent years, interest in plant-derived EVs has increas...
Article
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Helicobacter pylori (H. pylori) is a notorious, recalcitrant and silent germ, which can cause a variety of debilitating stomach diseases, including gastric and duodenal ulcers and gastric cancer. This microbe predominantly colonizes the mucosal layer of the human stomach and survives in the inhospitable gastric microenvironment, by adapting to this...
Article
Introduction: Biopredictive release tests are commonly used in the evaluation of oral medicines. They support decision-making in formulation development and allow predictions of the expected in-vivo performances. So far, there is limited experience in the application of these methodologies to injectable drug products. Areas covered: Parenteral d...
Article
Full-text available
Today, a growing number of computational aids and simulations are shaping model-informed drug development. Artificial intelligence, a family of self-learning algorithms, is only the latest emerging trend applied by academic researchers and the pharmaceutical industry. Nanomedicine successfully conquered several niche markets and offers a wide varie...
Article
Dermal delivery of bioactive molecules remains an attractive route of administration in osteoarthritis (OA) due to the local accumulation of drugs while avoiding their systemic side effects. In this study we propose a proniosome gel comprising non-ionic surfactants that self-assemble into de-hydrated vesicles for the delivery of the natural anti-in...
Article
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The emerging landscape of nanomedicine includes a wide variety of active pharmaceutical ingredients and drug formulations. Their design provides nanomedicines with unique features leading to improved pharmacokinetics and pharmacodynamics. They are manufactured using conventional or biotechnological manufacturing processes. Their physical characteri...
Article
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the hair follicles leading to painful lesions, associated with increased levels of pro-inflammatory cytokines. Numerous guidelines recommend antibiotics like clindamycin and rifampicin in combination, as first-line systemic therapy in moderate to severe forms of inflammation. H...
Article
Full-text available
The bioavailability of the antihypertensive drug valsartan can be enhanced by various microencapsulation methods. In the present investigation, valsartan-loaded polymeric nanoparticles were manufactured from Eudragit® RLPO using an emulsion–solvent evaporation method. Polyvinyl alcohol (PVA) was found to be a suitable stabilizer for the nanoparticl...
Article
Full-text available
Currently, a wide variety of complex non-oral dosage forms are entering the global healthcare market. Although many assays have been described in recent research, harmonized procedures and standards for testing their in vitro performance remain widely unexplored. Among others, dialysis-based techniques such as the Pharma Test Dispersion Releaser ar...
Article
For decades, there has been a growing interest in injectable subcutaneous formulations to improve the absorption of drugs into the systemic circulation and to prolong their release over a longer period. However, fluctuations in the blood plasma levels together with bioavailability issues often limit their clinical success. This warrants a closer lo...
Article
A growing number of nanomedicines entered the clinical trials and improved our understanding of the in vivo responses expected in humans. The in-vitro drug release represents an important critical quality attribute involved in pharmacokinetics. Establishing in vitro-in vivo relationships for nanomedicines requires a careful analysis of the clinical...
Article
Full-text available
Recently, bioinspired cell-derived nanovesicles (CDNs) have gained much interest in the field of nanomedicine due to the preservation of biomolecular structure characteristics derived from their parent cells, which impart CDNs with unique properties in terms of binding and uptake by target cells and intrinsic biological activities. Although the pro...
Article
For many years, nanomedicine is pushing the boundaries of drug delivery. When applying these novel therapeutics, safety considerations are not only a key concern when entering clinical trials but also an important decision point in product development. Standing at the crossroads, nanomedicine may be able to escape the niche markets and achieve wide...
Article
A wide variety of active pharmaceutical ingredients are released into the environment and pose a threat to aquatic organisms. Drug products using micro- and nanoparticle technology can lower these emissions into the environment by their increased bioavailability to the human patients. However, due to this enhanced efficacy, micro- and nanoscale dru...
Article
Full-text available
Targeted delivery of doxorubicin still poses a challenge with regards to the quantities reaching the target site as well as the specificity of the uptake. In the present approach, two colloidal nanocarrier systems, NanoCore-6.4 and NanoCore-7.4, loaded with doxorubicin and characterized by different drug release behaviors were evaluated in vitro an...
Article
Extracellular vesicles (EVs) are a class of cell-derived lipid-bilayer membrane vesicles secreted by almost all mammalian cells and involved in intercellular communication by shuttling various biological cargoes. Over the last decade, EVs – namely exosomes and microvesicles – have been extensively explored as next-generation nanoscale drug delivery...
Article
Over the last 30 years, hot melt extrusion has become a leading technology in the manufacture of amorphous drug delivery systems. Mostly applied as an ‘enabling formulation’ for poorly soluble compounds, application in the design of sustained-release formulations increasingly attracts the attention of the pharmaceutical industry. The drug candidate...
Chapter
Cell-derived Drug Delivery Systems (DDSs), particularly exosomes, have grown in popularity and have been increasingly explored as novel DDSs, due to their intrinsic targeting capabilities. However, clinical translation of exosomes is impeded by the tedious isolation procedures and poor yield. Cell-derived nanovesicles (CDNs) have recently been prod...
Article
Today, tacrolimus represents a cornerstone of immunosuppressive therapy for liver and kidney transplants and remains subject of preclinical and clinical investigations, aiming at the development of long-acting depot formulations for subcutaneous injection. One major challenge arises from establishing in vitro-in vivo correlations due to the absenc...
Article
Introduction Exosomes have been proven to alleviate myocardial ischemia reperfusion (I/R) injury in preclinical studies. However, the laborious and low-yield production process of naturally secreted exosomes has been impeding their translation into clinical trials. Purpose We aim to develop a simple and cost-effective protocol to produce exosome m...
Article
Cardiovascular disease remains the leading cause of morbidity and mortality globally. Extracellular vesicles (EVs), a group of heterogeneous nanosized cell-derived vesicles, have attracted great interest as liquid biopsy material for biomarker discovery in a variety of diseases including cardiovascular disease. Because EVs inherit bioactive compone...
Article
Today, environmental pollution with pharmaceutical drugs and their metabolites poses a major threat to the aquatic ecosystems. Active substances such as fenofibrate, are processed to pharmaceutical drug formulations before they are degraded by the human body and released into the wastewater. Compared to the conventional product Lipidil® 200, the ph...
Article
A hybrid gene delivery platform, micro Cell Vesicle Technology (mCVT), produced from the fusion of plasma membranes and cationic lipids, is presently used to improve the transfection efficiency of Hard-To-Transfect...
Article
Today, a growing number of subcutaneously administered depot formulations enable continuous delivery of poorly soluble compounds over a longer time period. The modified liberation is considered to be a rate-limiting step in drug absorption and thus impacts therapeutic efficacy and product safety. In the present approach, a mechanism-based pharmacok...
Article
Over the years, a wide variety of nanomedicines has entered global markets, providing a blueprint for the emerging generics industry. They are characterized by a unique pharmacokinetic behavior difficult to explain with conventional methods. In the present approach a physiologically-based nanocarrier biopharmaceutics model has been developed. Provi...
Article
Over the years, the performance of the liposomal formulations of temoporfin, Foslip® and Fospeg®, was investigated in a broad array of cell-based assays and preclinical animal models. So far, little attention has been paid to the influence of drug release and liposomal stability on the plasma concentration-time profile. The drug release is a key at...
Article
Nanomaterials have gained huge importance in various fields including nanomedicine. Nanoformulations of drugs and nanocarriers are used to increase pharmaceutical potency. However, it was seen that polymeric nanomaterials can cause negative effects. Thus, it is essential to identify nanomaterials with the least adverse effects on aquatic organisms....
Article
Full-text available
: Today, efficient delivery of sorafenib to hepatocellular carcinoma remains a challenge for current drug formulation strategies. Incorporating the lipophilic molecule into biocompatible and biodegradable theranostic nanocarriers has great potential for improving the efficacy and safety of cancer therapy. In the present study, three different techn...
Article
Today, a growing number of nanotherapeutics is utilized to deliver poorly soluble compounds using the intravenous route of administration. The drug release and the direct transfer of the active pharmaceutical ingredient to serum proteins plays an important role in bioavailability and accumulation of the drug at the target site. It is closely relate...
Article
After decades of research, nanotechnology has been used in a broad array of biomedical products including medical devices, drug products, drug substances, and pharmaceutical-grade excipients. But like many great achievements in science, there is a fine balance between the risks and opportunities of this new technology. Some materials and surface st...
Article
Foscan®, a formulation comprising temoporfin dissolved in a mixture of ethanol and propylene glycol, has been approved in Europe for palliative photodynamic therapy of squamous cell carcinoma of the head and neck. During clinical and preclinical studies it was observed that considering the administration route, the drug presents a rather atypical p...
Preprint
Full-text available
Background: Efficient delivery of the poorly water-soluble compound sorafenib still poses a challenge to current formulation strategies. To incorporate the lipophilic molecule into biocompatible and biodegradable theranostic nanoparticles has great potential for improving efficacy and safety of cancer therapy. Results: In this study, sorafenib nano...
Conference Paper
Full-text available
The workshop "Particle Characterization in Medicine and Biology" jointly organized by the Speakers from academia and industry gave insights into particle manufacture and characterization in various environments. Further, the implications for drug delivery and clinical translation of micro and nanotherapeutics were discussed.
Article
Since many drugs in the therapy scheme of multiple sclerosis (MS) are applied parenterally with significant side effects, oral treatment is the most accepted therapy option for chronic diseases like MS. The drug candidate TMP-001, which has disease-modifying properties, can be applied orally. Beside other symptoms, swallowing disorders have a major...
Article
For many years, delivering drug molecules across the blood brain barrier has been a major challenge. The neuropeptide nerve growth factor is involved in the regulation of growth and differentiation of cholinergic neurons and holds great potential in the treatment of stroke. However, as with many other compounds, the biomolecule is not able to enter...
Article
Novel drug delivery systems exhibit great potential in the formulation of poorly soluble compounds but also reduce the side effects of highly active drug molecules. Despite all efforts, there are only few technologies available to investigate the in vitro release of next-generation nanotherapeutics. In the following, different approaches for applic...
Chapter
Today, nanotechnology is widely applied by the pharmaceutical industry. Creating a new generation of products, there have been many concerns about the safety of these engineered functional nanomaterials some of which were used as diagnostics or in drug therapy. The regulatory authorities evaluated a wide range of analytical techniques to define the...
Article
Today, many of the newly developed pharmaceuticals and medical devices take advantage of nanotechnology and with a rising incidence of chronic diseases such as diabetes and cardiovascular disease, the number of patients afflicted globally with non-healing wounds is growing. This has created a requirement for improved therapies and wound care. Howev...
Article
As a growing number of nanotherapeutics enters the market, improved analytical techniques for measuring the drug release are required. Biorelevant release tests have become a standard in the prediction of in vivo pharmacokinetics but also in quality control of novel dosage forms. In the present study, two methods for testing the drug release from n...
Article
Full-text available
A rising number of nanopharmaceuticals have shown the potential of nanotechnology in the formulation of poorly soluble drugs as well as in the reduction of side effect of highly potent Active Pharmaceutical Ingredients (APIs). Despite steady progress, only few in vitro techniques enable prediction of the in vivo performance of nanotherapeutics. In...
Article
The dispersion releaser (DR) is a dialysis-based setup for the analysis of the drug release from nanosized drug carriers. It is mounted into dissolution apparatus 2 of the United States Pharmacopoeia. The present study evaluated the DR technique investigating the drug release of the model compound flurbiprofen from drug solution and from nanoformul...
Article
Full-text available
Despite all advances in drug delivery, the limitations of the analytical technologies involved in the characterization of next-generation nanomedicines are still impeding further progress of an emerging market. Discriminating between different formulations and batches, drug release is one of the most important quality criteria in development and qu...
Article
As a rapidly growing class of therapeutics, biopharmaceuticals have conquered the global market. Despite of the great potential from a therapeutic perspective, such formulations often require frequent injections due to their short half-life. Aiming to establish a parenteral dosage form with prolonged release properties, a biodegradable implant was...
Article
A rising number of new chemical entities that exhibit only poor aqueous solubility are identified in drug discovery processes. Polymeric micelles composed of block copolymers (BP) facilitate the delivery of such lipophilic molecules in drug therapy. Consequently, a rational screening and selection procedure for novel BP was established. Further, th...
Chapter
Full-text available
In recent years, significant effort has been made in the development and synthesis of polymer nanoparticles for the targeted delivery of drugs. Although many of these nanocarriers have attracted the attention of the pharmaceutical industry, only a few of them have been approved so far. The growing knowledge of their interactions with biological sur...
Article
The contribution of permeability and drug release to drug targeting were investigated in the course of development of a nanosized formulation of the anti-inflammatory compound TMP-001, for the local treatment in the gastrointestinal tract. TMP-001 was encapsulated by nanoprecipitation into Eudragit® RS 100. The permeability of these carriers was in...
Conference Paper
Full-text available
An apparatus based on the dialysis technique was specially designed for assessing in-vitro drug release of nanoparticles (NPs) by fluorescence measurement. The experimental setup provided continuous drug release profiles. A mathematical model was applied to process the data. With this method, the rate-limiting step caused by the transport of active...
Article
Full-text available
Radiation therapy is one of the most commonly used non-surgical intervention in tumor treatment and is often combined with other modalities to enhance its efficacy. Despite recent advances in radiation oncology, treatment responses, however, vary considerably between individual patients. A variety of approaches have been developed to enhance radiat...
Article
The development and manufacture of novel nanocarriers for drug delivery has proved challenging with regards to scale-up and pharmaceutical quality. Polymeric nanocarriers composed of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) were prepared and the photosensitizer meso-tetrakis(3-hydroxyphenyl) chlorin (mTHPC) was effectively e...
Article
The aim of the present investigation was to develop a reliable method which can be applied to the measurement of in-vitro drug release from nanocarriers. Since the limited membrane transport is one major obstacle to the assessment of drug release with dialysis techniques, the determination of this parameter was our objective. Therefore, a novel dru...
Article
Full-text available
Human serum albumin nanoparticles have been utilized as drug delivery systems for a variety of medical applications. Since ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents in magnetic resonance imaging, their encapsulation into the protein matrix enables the synthesis of diagnostic and theranostic agents by...
Article
Industrial production of nanosized drug delivery devices is still an obstacle to the commercialization of nanomedicines. This study encompasses the development of nanoparticles for peroral application in photodynamic therapy, optimization according to the selected product specifications, and the translation into a continuous flow process. Polymeric...
Article
During the past decade nanotechnology has become an essential part of formulation development in the pharmaceutical industry. Liposomes, micelles and nanoparticles have all been utilized to increase the bioavailability of drugs, reduce acute toxicity, and to target compounds to the site of action. Furthermore, a variety of excipients used in cosmet...
Article
Nanomaterials have become part of formulation development in the pharmaceutical industry and offer exciting opportunities in the area of targeted drug delivery. But they may also exert unexpected toxicities and potentially pose a threat to human health and the environment. Since the Scientific Committee on Emerging and Newly Identified Health Risks...
Article
Nanoparticles (NP) as carriers for anti-cancer drugs have shown great promise. Specific targeting of NP to malignant cells, however, remains an unsolved problem. Conjugation of antibodies specific for tumor membrane antigens to NP represents one approach to improve specificity and to increase therapeutic efficacy. In the present study, for the firs...
Article
The potency of many 5-lipoxygenase (5-LOX) inhibitors depends on the cellular peroxide tone and the mechanism of 5-LOX enzyme activation. Therefore, new inhibitors that act regardless of the mode of enzyme activation need to be developed. Recently, we identified a novel class of thiazolinone-based compounds as potent 5-LOX inhibitors. Here, we pres...
Article
Unlabelled: The specific application and transport of drugs into malignant tissue is a critical point during diagnosis and therapy. Nanoparticles are known as excellent drug carrier systems and offer the possibility of surface modification with targeting ligands, leading to a specific accumulation in the targeted tissue. First, the specificity of...
Article
Nanoparticles consisting of human serum albumin (HSA) play an emerging role in the development of new drug delivery systems. Many of these protein-based colloidal carriers are prepared by the well-known desolvation technique, which has shown to be a robust and reproducible method for the laboratory-scale production of HSA nanoparticles. The aim of...
Article
The photosensitizing efficiency of human serum albumin (HSA) nanoparticles loaded with the photosensitizers meta-tetra(hydroxy-phenyl)-chlorin (mTHPC) and meta-tetra(hydroxy-phenyl)-porphyrin (mTHPP) was investigated in vitro. The endocytotic intracellular uptake, and the time dependent drug release caused by nanoparticle decomposition of the PS lo...
Article
Controlled drug release is one of the main goals of recent developments in drug carrier systems. In this work human serum albumin (HSA) nanoparticles as carriers for 5-, 10-, 15-, 20-Tetrakis (3-hydroxyphenyl)-chlorin (mTHPC) were investigated. The photophysical properties of mTHPC-HSA nanoparticles in dependence of loading ratio and level of HSA c...