Article
Chemistry, Multidisciplinary
Shuying Wang, Griffin Downing, Karl F. Olsen, Tomi K. Sawyer, Roger D. Cone, Steven P. Schwendeman
Summary: This study developed a long-acting release formulation for setmelanotide using remote loading into PLGA microspheres. The loaded microspheres demonstrated slow and continuous peptide release, leading to long-term inhibition of food intake and body weight control in a diet induced obese murine model. This provides a promising treatment option for obesity.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Polymer Science
Maria Herrero-Herrero, Jose Antonio Gomez-Tejedor, Ana Valles-Lluch
Summary: Tailored membranes with a fiber diameter of 1.8 μm were electrospun from PLGA and PCLGA solutions by adjusting electrospinning and polymer solution parameters. PCLGA, with its amorphous morphology, required the addition of a salt to increase conductivity for successful electrospinning, presenting notable difficulties due to its structure. Interestingly, PCLGA, with a higher glycolic acid molar fraction, could be successfully electrospun, a feat not previously reported.
Article
Infectious Diseases
Flavia Pedrini, Virginia S. Nazato, Moema A. Hausen, Daniel Komatsu, Stela S. Pena, Ana Lidia M. Almeida, Fernanda J. C. Pirola, Marina P. Francoso, Eliana A. R. Duek
Summary: State-of-the-art sustained drug delivery systems aim to improve pharmacological transport by controlling the ratio between drug release and therapeutic effect. Biodegradable polymer microspheres like PLGA play a crucial role in directing drug release to specific regions of interest.
Article
Biotechnology & Applied Microbiology
Heejun Park, Eun-Sol Ha, Jeong-Soo Kim, Min-Soo Kim
Summary: The study aimed to develop an improved sustained-release PLGA microsphere of exenatide using supercritical fluid extraction of emulsions (SFEE). The effect of various process parameters on the fabrication of exenatide-loaded PLGA microspheres was investigated using the Box-Behnken design. The results showed that the SFEE process improved the properties of PLGA microspheres, including smaller particle size, higher encapsulation efficiency, and lower burst release.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Materials Science, Multidisciplinary
Akhand Pratap Singh, Om Prakash, Sunil Kumar, Aparna Shukla, Pralay Maiti
Summary: The study demonstrates the suitability of poly(lactic acid-co-glycolic acid) (PLGA) as a sustained drug delivery vehicle for melanoma treatment. PLGA nanoparticles (NPs) and PLGA film encapsulated with paclitaxel (PTX) show greater efficacy in inhibiting melanoma cell proliferation and reducing tumor volume, compared to pure drug and control group. The sustained drug delivery systems also result in minimal damage to vital organs and fewer side effects.
MATERIALS TODAY COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Chisong Lee, Jinkyung Kim, Daniel Junmin Um, Youseong Kim, Hye Su Min, Jiwoo Shin, Jee Hye Nam, Geonwoo Kang, Mingyu Jang, Huisuk Yang, Hyungil Jung
Summary: The study introduced a novel heat-melting method to fabricate hydrophobic PLGA DMNs for transdermal drug delivery, avoiding potentially harmful organic solvents. The implanted HMP-DMNs successfully separated from the patch within 10 minutes and released encapsulated molecules for nearly 4 weeks, demonstrating safe and effective sustained drug delivery without the use of organic solvents. This research offers an innovative approach to utilizing PLGA as a material for transdermal drug delivery systems.
Article
Polymer Science
Jie Yan, Paula Facal Marina, Anton Blencowe
Summary: Poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-PLGA) block copolymers and their thermoresponsive hydrogels have been widely studied for sustained drug delivery. The microstructure of these copolymers is highly sensitive to the reaction conditions, such as temperature and catalyst loading, which influence the occurrence and extent of side reactions during ring-opening polymerization. Our detailed study revealed that increasing the catalyst loading had negligible effects on side reactions but surprisingly increased the polymerization rate of lactide relative to glycolide. These findings provide valuable insights for the improved synthesis of PLGA-PEG-PLGA copolymers and their hydrogels.
Article
Multidisciplinary Sciences
Morgan Giles, Justin Hong, Yayuan Liu, Jie Tang, Tinghui Li, Avital Beig, Anna Schwendeman, Steven Schwendeman
Summary: Encapsulation of bioactive peptides in slow-release particles is achieved through a simple and low-cost method of remote encapsulation using polymer phase absorption. This technique allows for extended duration of action of peptide drugs and eliminates the need for organic solvents and critical removal steps.
NATURE COMMUNICATIONS
(2022)
Article
Engineering, Biomedical
Shengtang Li, Xuewen Shi, Bo Xu, Jian Wang, Peng Li, Xin Wang, Jinpeng Lou, Ziyao Li, Chengwei Yang, Songkai Li, Ping Zhen
Summary: This study prepared vancomycin-loaded PLGA microspheres with silk fibroin (SF) coating and investigated their in vitro drug release behavior. The results showed that SF coating could alleviate the initial burst release and reduce the cumulative drug release of the microspheres, potentially prolonging the drug action time and improving the anti-infection effect.
JOURNAL OF BIOMATERIALS APPLICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Yiye Lu, Geoffrey W. Coates
Summary: Poly(lactic-co-glycolic acid) (PLGA) is widely used in various biomedical applications due to its biodegradability and biocompatibility. This study successfully developed a method to synthesize syndioenriched, alternating PLGA from racemic methyl-glycolide (rac-MeG), and confirmed the high degree of alternation of the comonomer sequence and moderate syndiotacticity within the polymer backbone stereoconfiguration through NMR investigations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Yiye Lu, Geoffrey W. Coates
Summary: Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable and biocompatible polymer used in biomedical applications. This study presents a method for synthesizing syndioenriched, alternating PLGA from racemic methyl-glycolide with the use of an optimized racemic aluminum catalyst. The resulting material has a high degree of alternation in copolymer sequence and moderate syndiotacticity, and is amorphous, making it suitable for drug complexation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Eswaramoorthy Thirumalaikumar, S. Vimal, Ramamoorthy Sathishkumar, M. Ravi, V. Karthick, S. Ramya, John Thomas, Vinay Kumar, Chinnaperumal Kamaraj, Thavasimuthu Citarasu
Summary: Encapsulation of DNA vaccines onto carriers enhances antigen immunogenicity. In this study, DNA vaccines were loaded onto biodegradable polymer microspheres and delivered to goldfish, resulting in improved innate immune response and survival rate.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Multidisciplinary
Shuaikai Ren, Chunxin Wang, Liang Guo, Congcong Xu, Yan Wang, Changjiao Sun, Haixin Cui, Xiang Zhao
Summary: Microcapsules with uniform size and tailored dimensions were prepared using emulsification and solvent evaporation methods in this study for the construction of controlled-release drug carriers. Morphology and structure of the microcapsules could be tailored by regulating the preparation conditions, and the release rate of protein could be controlled by adjusting the pore size. This controlled-release novel microcapsule carrier system shows great potential for biomedical applications.
Article
Chemistry, Physical
Guangliang Liu, Roberto Martinez, Anika Bhatnagar, Kathleen McEnnis
Summary: PLGA is a commonly used drug carrier in nanomedicines due to its biodegradability, biocompatibility, and low toxicity. The glass transition temperature (T-g), which is an indicator of drug release behavior, is often overlooked in the physico-chemical characterization and study of drug release. This study investigated the influence of polymeric (PVA) and ionic (DMAB) surfactants on the T-g of PLGA nanoparticles and found that the choice and residual amount of surfactant are crucial parameters in designing the physico-chemical properties of PLGA particles.
Article
Materials Science, Multidisciplinary
Sama J. AL-zuwaini, Faramarz Mehrnejad, Zahra Lotfi-Sousefi, Ali Hossein Rezayan, Mohammad Barshan-tashnizi
Summary: In this study, the impact of biocompatible synthetic polymers on the structure and dynamics of L-asparaginase was investigated using molecular dynamics simulations. The results demonstrate that the protein encapsulated in PLGA is more stable than in MPEG, primarily due to electrostatic interactions between the enzyme and PLGA. Hydrophobic and vdW interactions are the driving force for the protein-MPEG interaction. The study also highlights the critical roles of the protein's basic residues in the encapsulation mechanism.
MATERIALS TODAY COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Judith Menth, Martin Maus, Karl G. Wagner
Summary: This study investigates the effects of equipment and process parameter changes on the visual defects of tablets produced during a twin screw wet granulation process. The results show that changes leading to a reduction in defect rate correlate with a decrease in wall friction angle. Wall friction measurements can be a powerful tool for equipment selection and process optimization.
Article
Chemistry, Medicinal
Lukas M. Gockel, Vladlena Pfeifer, Fabian Baltes, Rafael D. Bachmaier, Karl G. Wagner, Gerd Bendas, Michael Guetschow, Izidor Sosic, Christian Steinebach
Summary: This research presents a novel approach to treating prostate cancer by exploiting the ubiquitin-proteasome system to degrade specific proteins. By modifying the exit vector, the study successfully demonstrated the potent degradation of androgen receptor in lung cancer cells. These findings provide valuable insights for further investigation into the involvement of androgen receptor in lung cancer models.
ARCHIV DER PHARMAZIE
(2022)
Article
Pharmacology & Pharmacy
Marius J. Kreiser, Christoph Wabel, Karl G. Wagner
Summary: The continuous manufacturing of solid oral-dosage forms is an emerging technology in the pharmaceutical industry. This study investigated the impact of blender variables on the mixing step and subsequent continuous manufacturing process steps. Significant impacts on mixing parameters, material attributes, tableting parameters, and tablet properties were found. The study also evaluated the relationships between these process parameters.
Article
Pharmacology & Pharmacy
Barbara Schoenfeld, Ulrich Westedt, Benjamin-Luca Keller, Karl G. Wagner
Summary: This study explored the potential of vacuum drum drying (VDD) as a drying technique for solidifying nanosuspensions. The impact of drying protectants on the processibility of VDD, powder properties, redispersibility, and crystallinity was investigated. The results showed that the glass transition temperature of the drying protectant had a clear impact on the redispersibility and crystallinity of the VDD intermediate. The high T-g-substances trehalose and lactose showed better performance than mannitol at higher drum temperatures.
Article
Pharmacology & Pharmacy
Barbara Schoenfeld, Ulrich Westedt, Karl G. Wagner
Summary: This study found that the particle density of polymeric excipients may exceed the standard at low compaction pressures, while other brittle fillers only reach the particle density level after surpassing a certain pressure. The linear increase in elastic recovery with increasing compaction pressure can be used to calculate the elastic modulus.
Article
Pharmacology & Pharmacy
Kevin Kayser, Marius Monschke, Karl G. Wagner
Summary: Process simulation is crucial for scaling up and understanding the critical parameters of hot-melt extrusion. Knowledge of material properties is essential for performing accurate numerical simulations. In this study, the optimal sample preparation method for small amplitude oscillatory shear rheological measurements was investigated, and vacuum compression molding (VCM) was found to yield the most similar results between simulated and experimental values.
Article
Pharmacology & Pharmacy
Tim Becker, Anna K. Krome, Sahel Vahdati, Andrea Schiefer, Kenneth Pfarr, Alexandra Ehrens, Tilman Aden, Miriam Grosse, Rolf Jansen, Silke Alt, Thomas Hesterkamp, Marc Stadler, Marc P. Huebner, Stefan Kehraus, Gabriele M. Koenig, Achim Hoerauf, Karl G. Wagner
Summary: The in vivo studies in mice are a valuable model for testing new drug ingredients, but the lack of preclinical in vitro evaluations of drug formulations in mice is a gap in research. The development of novel in vitro and in silico models has supported the evaluation of the anti-infective drug CorA. The study found that the solubility of CorA in mice was lower compared to human-specific media, and the solubility was limited by the formulation. The pharmacokinetic studies in mice correlated with the in vitro dissolution prediction and ruled out intestinal efflux transport.
Article
Chemistry, Multidisciplinary
Yomnah Y. Elsayed, Toni Kuhl, Katharina Dauer, Alina Sayin, Karl G. Wagner, Diana Imhof
Summary: This study optimized protein analysis methods to investigate the stability and function of lysozyme in a formulated form. The findings showed that lysozyme exhibited high stability at different temperatures and storage times when formulated using hot-melt extrusion. These findings suggest that hot-melt extrusion is a suitable alternative for preserving the properties and stability of lysozyme. The methods and workflow used in this study can be applied to assess the usability and compatibility of other protein drugs for different pharmaceutical applications.
Article
Pharmacology & Pharmacy
Florian Poestges, Kevin Kayser, Jan Appelhaus, Marius Monschke, Michael Gutschow, Christian Steinebach, Karl G. G. Wagner
Summary: PROteolysis TArgeting Chimaeras (PROTACs) provide new possibilities in modern medicine for targeting undruggable proteins. However, due to their hydrophobic structure, PROTACs often have low solubility and oral bioavailability is still challenging. In addition, limited drug supply hinders formulation development. This study investigates the solubility enhancement of the prototypic PROTAC ARCC-4 using mini-scale formulations of amorphous solid dispersions (ASDs) and liquisolid formulations. The results show that ASD formation using suitable polymers can effectively improve the solubility of PROTACs, while liquisolid formulations fail to enhance solubility.
Article
Pharmacology & Pharmacy
Florian Poestges, Kevin Kayser, Edmont Stoyanov, Karl G. Wagner
Summary: A current trend in the development of amorphous solid dispersions (ASDs) is the combination of two polymers for synergistic enhancement in supersaturation of poorly soluble drugs. This study investigated the supersaturation potential of celecoxib (CXB) using combinations of methacrylic acid-ethyl acrylate copolymer (1:1) (EL 100-55) and hydroxypropyl cellulose (HPC) SSL. The results showed that the combination of both polymers led to a boost of CXB solubility, with the most promising results obtained using a 50:50 polymer ratio. HPC SSL was identified as a suitable precipitation inhibitor for fast dissolving CXB: EL 100-55 ASD, and further dissolution improvement was achieved with ternary ASDs processed by hot melt extrusion (HME), which led to synergistic interactions and enhanced CXB supersaturation.
INTERNATIONAL JOURNAL OF PHARMACEUTICS-X
(2022)
Article
Pharmacology & Pharmacy
Marius J. Kreiser, Christoph Wabel, Karl G. Wagner
Summary: Continuous manufacturing of solid oral dosage forms has gained popularity in the pharmaceutical industry and a statistical model has been developed to investigate its process parameters and resulting product. The study revealed optimal process conditions for the mixer through the combination of high throughput and low impeller speed. Material attributes, such as bulk density, were found to significantly impact the continuous manufacturing process. Simplified linear models were also developed to accurately predict input bulk density.
Article
Pharmacology & Pharmacy
Marius Neuwirth, Sebastian K. Kappes, Michael U. Hartig, Karl G. Wagner
Summary: In this study, the properties and performance of spray-dried ASDs and coated ASDs were compared. The results showed that spray-dried ASDs had similar physical stability and dissolution performance as coated ASDs. Therefore, ASD-layered pellets are an attractive option for ASD formulation.
Article
Agriculture, Multidisciplinary
Marvin Benedikt Brenner, Sandra Flory, Matthias Wuest, Jan Frank, Karl Wagner
Summary: Currently, there is a lack of in vitro dissolution methods that can accurately predict the in vivo bioavailability of compounds from complex mixtures. This study developed an in vivo predictive dissolution method (BiPHa+) using data on the in vivo performance of bioavailability-improved curcumin formulations. Compared with conventional dissolution systems, BiPHa+ demonstrated superior in vivo-relevant formulation characterization and had the highest degree of linearity in predicting bioavailability. It also provided mechanistic information about formulation-dependent release characteristics.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Katharina Dauer, Christian Werner, Dirk Lindenblatt, Karl Gerhard Wagner
Summary: Due to limited stability of protein-based therapeutics in liquid formulations, there is increasing interest in the development of solid protein formulations for improved stability. This study used small-scale ram and twin-screw extrusion to stabilize proteins in PEG-matrices. Various analytical methods were employed to assess protein stability in the extrudates and compare different formulation and process parameters. The results showed that melt extrusion had varying impacts on the conformational stability of different proteins, with ram extrusion being a preferred method for preparing highly-loaded solid protein formulations.
INTERNATIONAL JOURNAL OF PHARMACEUTICS-X
(2023)
Review
Biochemistry & Molecular Biology
Anna K. Krome, Tim Becker, Stefan Kehraus, Andrea Schiefer, Michael Gutschow, Lillibeth Chaverra-Munoz, Stephan Huttel, Rolf Jansen, Marc Stadler, Alexandra Ehrens, Domen Pogorevc, Rolf Muller, Marc P. Hubner, Thomas Hesterkamp, Kenneth Pfarr, Achim Hoerauf, Karl G. Wagner, Gabriele M. Konig
Summary: From August 1984 to January 2022, there has been a worldwide increase in morbidity and mortality caused by antibiotic-resistant microbial infections. Effective prevention and control of infectious diseases, along with appropriate use of approved antibacterial drugs, are vital. The continuous development and supply of novel antibiotics are urgently needed. This review focuses on the discovery and development of corallopyronin A, a natural antibiotic compound, and highlights its potential as a preclinical candidate for the treatment of human filarial infections.
NATURAL PRODUCT REPORTS
(2022)
