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Herbal Product Development and Characteristics
Published in Anil K. Sharma, Raj K. Keservani, Surya Prakash Gautam, Herbal Product Development, 2020
Mirian Pateiro, Rubén Domínguez, Predrag Putnik, Danijela Bursać Kovačević, Francisco J. Barba, Paulo S. E. Munekata, Elena Movilla Fierro, José M. Lorenzo
Chemical composition of the nutraceuticals from Lamiaceae family determines their characteristics, and therefore their mode of action. Even though there are several BACs from several structural groups, their composition makes it very difficult to establish a single mechanism of action (Wink, 2015). However, to explain general mode of action, it is usual to associate physiological effects with the main present components. In this case, phenolic compounds, which represent around 85% of their total composition, are the main BACs involved (Bakkali et al., 2008). Therefore, noncovalent modification of proteins, interaction with biomembranes and free-radical scavengers, represent the typical modes of action (Figure 8.3).
Essential Oils and Volatiles in Bryophytes
Published in K. Hüsnü Can Başer, Gerhard Buchbauer, Handbook of Essential Oils, 2020
Agnieszka Ludwiczuk, Yoshinori Asakawa
It is, however, necessary to mention that a very small fraction of bryophytes has been tested for their pharmacological efficacy. Although the exact mode of action of some of described bioactive compounds remains unknown, bryophytes could serve as an attractive candidate for therapeutic properties. Further work on isolation, characterization, structural elucidation, pharmacological evaluation, determination of mode of action, and clinical trial of these active principles could open an exciting aspect of future drug-development programs.
Microneedles for Drug Delivery
Published in Tapash K. Ghosh, Dermal Drug Delivery, 2020
Lisa A. Dick, Daniel M. Dohmeier, Ann M. Purrington, Scott A. Burton
Combination product designations for these systems are likely defined as either single integrated [3.2(e)(1)] or co-packaged [3.2(e)(2)] combination products or a combination of these two types. Microneedle systems utilize the component or device constituent to administer the agent for the desired effect by the drug or biologic. The primary mode of action of these combination products is the drug or biologic. In the case of solid microneedle systems where the therapeutic agent is coated on the microneedle array and delivery is assisted by a power-supplied applicator, the array component is a primary packaging component with a delivery function, when used in concert with the applicator. The array component is integrated in the adhesive patch, all of which are supported with the use of a backing. The applicator is a device which is designed for the specific use with the microneedle patch and for the identified drug product. Due to the unique characteristics of the applicator in relation to its usage with only the planned coated microneedle patch, the applicator would gain market authorization in the NDA or BLA of the complete combination product. It is likely in this example that the solid microneedle combination product would be categorized 3.2(e)(2), when the applicator would be co-packaged with the coated microneedle patch. Some interpretations may consider the patch containing the microstructures a 3.2(e)(1) product on its own, however as described earlier in this chapter, solid microneedle systems benefit from inclusion of an applicator for uniform delivery.
Non-human primates in the PKPD evaluation of biologics: Needs and options to reduce, refine, and replace. A BioSafe White Paper
Published in mAbs, 2022
Karelle Ménochet, Hongbin Yu, Bonnie Wang, Jay Tibbitts, Cheng-Pang Hsu, Amrita V. Kamath, Wolfgang F. Richter, Andreas Baumann
Targeting the CD28 pathway has been considered high risk since 2006, when TeGenero’s CD28 superagonist mAb (TGN1412) caused severe cytokine release syndrome resulting in long-term damage in 6 healthy volunteers during a Phase 1 clinical trial.40, 41 Using a pharmacologically based method to establish the FIH starting dose, such as the MABEL approach, is recommended for targets that likely lead to a biological cascade or cytokine release with an amplification.7 As an antagonist, lack of agonism or costimulatory activity and inhibiting CD28-mediated T-cell proliferation and cytokine production, lulizumab pegol was not anticipated to cause any amplified cytokine release.42 However, given the inherent risk of targeting CD28, a MABEL approach was conservatively adopted to select the FIH starting dose.43 The challenges associated with the MABEL approach included: 1) assessing potential differences of sensitivity for the mode of action (preferably under physiological relevant conditions) between human and animals; 2) identifying a relevant animal model to establish in vitro to in vivo correlation in target engagement (e.g., dissociation constant (Kd), receptor occupancy (RO), and concentration leading to 50% of maximum effect (EC50)); and 3) identifying a translational PD marker for functional activities. This example illustrates how the NHP PKPD data, including systemic exposure, extent of RO, PD activities, and duration of effect, played a critical role in the FIH dose selection.
Assessing the immunosuppressive activity of alginate-encapsulated mesenchymal stromal cells on splenocytes
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2022
Sandhya Moise, Luigi Dolcetti, Francesco Dazzi, Paul Roach, Lee Buttery, Sheila MacNeil, Nick Medcalf
The therapeutic benefit of MSCs is highly promising for future healthcare, although the delivery of such a treatment is complicated due to the various cell and material parameters that must be optimised. The current study demonstrates that MSCs can suppress the proliferation of activated splenocytes purely through an indirect mode and this effect is sustained for over a week with repeated exposure to new batches of immune cells. This provides a strong foundation for designing biomaterial-encapsulated MSCs to deliver their immunosuppressive activity. Specifically, by engineering the biomaterial composition, architecture, and encapsulation route, it will be possible to facilitate sustained and controlled immunosuppression. The biomaterial can be designed to degrade at a predetermined rate to initially enable the paracrine mode of MSCs’ immunosuppression followed by a slow release of the cells into the milieu to achieve the more potent direct mode of immunosuppression. Further studies are required to assess the potential of combined modes of action. They will occur at different rates, and potentially circumvent an immediate loss of the MSCs due to migration and/or apoptosis whilst enabling a stronger as well as a more sustained response for efficient long-term immunosuppression.
An update on the pharmacological management of autoimmune hepatitis
Published in Expert Opinion on Pharmacotherapy, 2021
Yooyun Chung, Mussarat N Rahim, Jonathon J Graham, Yoh Zen, Michael A Heneghan
Nevertheless, we are in a fascinating era where new immunomodulatory therapies are being introduced into clinical practice. These new therapies could significantly impact the way in which we manage AIH [97]. Stratification of patients into groups who would most likely benefit from certain therapies (different modes of action) is also desirable. Ultimately, we desire a personalized medicine approach to care in AIH patients, as well as reducing side effects and improving quality of life are key measures. Finite curative first-line therapies for AIH is the eventual goal, so that we can move away from life-long treatment with corticosteroids and immunosuppression. Although a cure for AIH seems a faraway concept, improving the therapeutic armamentarium to manage these complex patients in the interim is a necessity. We therefore need an international collaborative approach between pharma industry, patient groups, and clinicians when designing these clinical trials.