Maike Windbergs

3D printed tablets loaded with polymeric nanocapsules: An innovative approach to produce customized drug delivery systems

The generation of multi-functional drug delivery systems, namely solid dosage forms loaded with nano-sized carriers, remains little explored and is still a challenge for formulators. For the first time, the coupling of two important technologies, 3D printing and nanotechnology, to produce innovative solid dosage forms containing drug-loaded nanocapsules was evaluated here. Drug delivery devices were prepared by fused deposition modelling (FDM) from poly(ε-caprolactone) (PCL) and Eudragit® RL100 (ERL) filaments with or without a channelling agent (mannitol). They were soaked in deflazacort-loaded nanocapsules (particle size: 138nm) to produce 3D printed tablets (printlets) loaded with them, as observed by SEM. Drug loading was improved by the presence of the channelling agent and a linear correlation was obtained between the soaking time and the drug loading (r2=0.9739). Moreover, drug release profiles were dependent on the polymeric material of tablets and the presence of the channelling agent. In particular, tablets prepared with a partially hollow core (50% infill) had a higher drug loading (0.27% w/w) and faster drug release rate. This study represents an original approach to convert nanocapsules suspensions into solid dosage forms as well as an efficient 3D printing method to produce novel drug delivery systems, as personalised nanomedicines.

Functional electrospun fibers for the treatment of human skin wounds

Graphical abstract Figure. No Caption available. Abstract Wounds are trauma induced defects of the human skin involving a multitude of endogenous biochemical events and cellular reactions of the immune system. The healing process is extremely complex and affected by the patient’s physiological conditions, potential implications like infectious pathogens and inflammation as well as external factors. Due to increasing incidence of chronic wounds and proceeding resistance of infection pathogens, there is a strong need for effective therapeutic wound care. In this context, electrospun fibers with diameters in the nano‐ to micrometer range gain increasing interest. While resembling the structure of the native human extracellular matrix, such fiber mats provide physical and mechanical protection (including protection against bacterial invasion). At the same time, the fibers allow for gas exchange and prevent occlusion of the wound bed, thus facilitating wound healing. In addition, drugs can be incorporated within such fiber mats and their release can be adjusted by the material and dimensions of the individual fibers. The review gives a comprehensive overview about the current state of electrospun fibers for therapeutic application on skin wounds. Different materials as well as fabrication techniques are introduced including approaches for incorporation of drugs into or drug attachment onto the fiber surface. Against the background of wound pathophysiology and established therapy approaches, the therapeutic potential of electrospun fiber systems is discussed. A specific focus is set on interactions of fibers with skin cells/tissues as well as wound pathogens and strategies to modify and control them as key aspects for developing effective wound therapeutics. Further, advantages and limitations of controlled drug delivery from fiber mats to skin wounds are discussed and a future perspective is provided.

Tracing molecular and structural changes upon mucolysis with N-acetyl cysteine in human airway mucus

The conducting airways of the human lungs are lined by mucus, which lubricates the lung epithelium and provides a first-line protection against airborne threats. As a novel approach for visualization of the human mucus microstructure, we applied confocal Raman microscopy as a label-free and chemically selective technique. We were successfully able to chemically resolve the pulmonary surfactant from the mucus matrix and show its spatial distribution, as well as to visualize the structural changes within the freeze-dried mucus mesh upon chemical mucolysis. Subsequently, we performed rheological measurements before and after mucolysis and correlated morphology and chemical structure of the mucus with its rheological characteristics. These results do not only enrich the knowledge about the mucus microstructure, but can also, significantly contribute to rational development of future lung therapeutics.

Raman spectroscopy in pharmaceutical research and industry

Abstract In the fast-developing fields of pharmaceutical research and industry, the implementation of Raman spectroscopy and related technologies has been very well received due to the combination of chemical selectivity and the option for non-invasive analysis of samples. This chapter explores established and potential applications of Raman spectroscopy, confocal Raman microscopy and related techniques from the early stages of drug development research up to the implementation of these techniques in process analytical technology (PAT) concepts for large-scale production in the pharmaceutical industry. Within this chapter, the implementation of Raman spectroscopy in the process of selection and optimisation of active pharmaceutical ingredients (APIs) and investigation of the interaction with excipients is described. Going beyond the scope of early drug development, the reader is introduced to the use of Raman techniques for the characterization of complex drug delivery systems, highlighting the technical requirements and describing the analysis of qualitative and quantitative composition as well as spatial component distribution within these pharmaceutical systems. Further, the reader is introduced to the application of Raman techniques for performance testing of drug delivery systems addressing drug release kinetics and interactions with biological systems ranging from single cells up to complex tissues. In the last part of this chapter, the advantages and recent developments of integrating Raman technologies into PAT processes for solid drug delivery systems and biologically derived pharmaceutics are discussed, demonstrating the impact of the technique on current quality control standards in industrial production and providing good prospects for future developments in the field of quality control at the terminal part of the supply chain and various other fields like individualized medicine. On the way from the active drug molecule (API) in the research laboratory to the marketed medicine in the pharmacy, therapeutic efficacy of the active molecule and safety of the final medicine for the patient are of utmost importance. For each step, strict regulatory requirements apply which demand for suitable analytical techniques to acquire robust data to understand and control design, manufacturing and industrial large-scale production of medicines. In this context, Raman spectroscopy has come to the fore due to the combination of chemical selectivity and the option for non-invasive analysis of samples. Following the technical advancements in Raman equipment and analysis software, Raman spectroscopy and microscopy proofed to be valuable methods with versatile applications in pharmaceutical research and industry, starting from the analysis of single drug molecules as well as complex multi-component formulations up to automatized quality control during industrial production.

Raman Spectroscopy in Skin Research and Dermal Drug Delivery

Raman spectroscopy represents an upcoming analytical technique in the field of skin research and dermal drug delivery. In the last few decades, significant progress in optical equipment like lasers and detectors as well as in microscopy and software development paved the way for chemically selective three-dimensional Raman imaging with high spatial resolution. Potential applications range from analysis of physiological and pathophysiological skin conditions (e.g. non-destructive cancer detection in clinics) up to surgery guidance. In the field of drug delivery and cosmetics , Raman microscopy is successfully applied for investigating interactions with skin as well as for elucidation of drug penetration kinetics within the different skin tissue layers, thus strongly supporting rational development and improving product safety of novel skin therapeutics. This chapter provides a brief introduction about skin anatomy and dermal drug delivery systems, as well as state-of-the-art analytics in skin research. Furthermore, the potential of Raman spectroscopy for application in skin research, particularly its advantages and limitations in the field, is comprehensively elaborated. Subsequently, an overview about skin research studies applying Raman spectroscopy is given comprising various in vitro as well as in vivo implementations. Finally, employment of Raman spectroscopy for advanced diagnosis and surgery guidance are discussed and a future perspective in the field of skin research is given.

Multifunctional electrospun nanofibers for wound application – Novel insights into the control of drug release and antimicrobial activity

Graphical abstract Figure. No caption available. &NA; Therapeutic management of skin wounds is still faced with major challenges associated with chronicity and bacterial infection. Consequently, there is a high clinical need for effective therapeutic approaches addressing these aspects. In this context, electrospun fibers emerged as beneficial carrier systems for local and controlled delivery of wound healing agents, additionally providing a protective barrier against bacterial invasion. However, depending on the material, such fibers were also shown to provide a potential substrate for bacterial colonization and growth. Thus, profound understanding of fiber characteristics and the respective interactions of fibers with biological systems, cells as well as bacteria, is of major importance. To address these issues, we designed drug‐loaded hybrid fibers consisting of polycaprolactone (PCL) and chitosan. Pure PCL fibers provided suitable drug release kinetics for wound healing, but were colonized by Pseudomonas bacteria which were used as model pathogens. The addition of chitosan to the fiber matrix reduced the number of adherent bacteria by tenfold compared to pure PCL fibers and did not show any adverse effects to human skin cells. Further, chitosan incorporation significantly improved fiber hydrophilicity, identified as one of the key regulators of optimized cell‐fiber interactions. We successfully encapsulated dexpanthenol as an established wound healing active into these hybrid fibers and solvent polarity was found to be a key factor for controlling drug release kinetics from the fibers. For the final formulation, controlled drug release over seven days with a burst release of 11.54% within 3 h could be achieved and the wound healing effect of the fiber mats could successfully be demonstrated in a cell‐based wound healing assay as a proof‐of‐concept. Such multifunctional fibers simultaneously deliver actives and prevent bacterial growth, and consequently show a high potential for future wound therapy.

Influence of polymer composition and drug loading procedure on dual drug release from PLGA:PEG electrospun fibers

ABSTRACT Poly(lactide‐co‐glycolide) (PLGA) has been widely investigated for fabricating electrospun fibers due to their biocompatibility, paired with the capacity for encapsulating different drugs. However, such scaffolds shrink and distort upon contact with biological media, which is undesired for local drug application. To address this issue, we fabricated composite fiber scaffolds with the combination of PLGA and poly(ethylene glycol) (PEG). Scaffold shrinkage could successfully be overcome, however, the release kinetics of the encapsulated drug was strongly dependent on the amount of PEG. The addition of 5% PEG resulted in slower drug release due to a significant increase in fiber diameters. In contrast, the drug release rate was accelerated for fibers containing 10% PEG due to the water‐soluble nature of the polymer. Furthermore, co‐delivery of two different drugs, the small molecule acyclovir and the model protein bovine serum albumin was realized by two different approaches, coaxial electrospinning and immobilization of the drugs on the surface of the fibers, and drug release was found to be strongly dependent on the loading procedure. Based on our findings, key factors for understanding and controlling physicochemical properties of PLGA/PEG composite fibers as well as tuning drug release could be identified, providing an essential basis for rational design of electrospun fiber‐based drug carriers.

Hyperspectral imaging of drug delivery

In the field of pharmaceutical research, confocal Raman microscopy recently attracted a lot of attention for non-invasive and three-dimensional imaging. In contrast to fluorescence microscopy generally requiring bulky labels which often change physicochemical properties of drugs impeding predictive analysis, Raman microscopy is inherently chemically selective. Applications range from drug distribution in delivery systems like tablets up to interactions of cells and tissue with drug carriers as well as their uptake.

Delivery of Therapeutic Proteins Using Electrospun Fibers—Recent Developments and Current Challenges

Proteins play a vital role within the human body by regulating various functions and even serving as structural constituent of many body parts. In this context, protein‐based therapeutics have attracted a lot of attention in the last few decades as potential treatment of different diseases. Due to the steadily increasing interest in protein‐based therapeutics, different dosage forms were investigated for delivering such complex macromolecules to the human body. Here, electrospun fibers hold a great potential for embedding proteins without structural damage and for controlled release of the protein for therapeutic applications. This review provides a comprehensive overview of the current state of protein‐based carrier systems using electrospun fibers, with special emphasis on discussing their potential and key challenges in developing such therapeutic strategies, along with a prospective view of anticipated future directions.