Denise Steiner

Background/Objectives: Glioblastoma multiforme (GBM) remains the most aggressive and treatment-refractory primary brain tumor, with current therapeutic modalities providing minimal survival improvement. Chimeric antigen receptor (CAR)-based immunotherapies succeeded in hematologic malignancies but are constrained in solid tumors by tumor heterogeneity, immunosuppressive microenvironment, and delivery challenges. CD276 (B7-H3), a pan-cancer antigen overexpressed in gliomas and correlated with poor patient outcomes, represents a compelling immunotherapeutic target. Methods: Here, we developed a non-viral lipid nanoparticle (LNP)-based platform for transient CAR mRNA delivery to T cells and evaluated its application for generating CD276 (B7-H3)-targeted CAR-T cells against GBM. An in-house-assembled T-mixer incorporating polyether ether ketone (PEEK) tubing was integrated with a dual-syringe-pump system for controlled LNP production. Results: LNPs formulated with clinically relevant ionizable lipids, SM-102 and DLin-MC3-DMA, demonstrated high encapsulation efficiency and effective mRNA delivery. Cell-type-dependent expression kinetics were further characterized following LNP-mediated reporter mRNA delivery in K562, NK, NK92, and T cells, revealing differences in transgene expression across cell populations. LNP-mediated delivery of CD276 CAR mRNA enabled generation of CAR-expressing T cells that exhibited antigen-specific cytotoxicity against CD276-positive LN229 GBM cells in vitro. Conclusions: Collectively, this study demonstrates the feasibility of an adaptable LNP-based platform for non-viral CAR mRNA engineering of T cells and CD276-targeted cytotoxicity against GBM cells in vitro. The combination of transient CAR expression and LNP-mediated mRNA delivery provides a foundation for further optimization and evaluation in preclinical in vivo models.

Background: Linear atrophic scars, resulting from surgical or traumatic injuries, are characterized by dermal depression, pigmentation changes, and psychosocial burden. While their early treatment has been hypothesized to yield better outcomes due to heightened tissue responsiveness during the proliferative healing phase, optimal timing for therapeutic intervention remains unclear. Objective: To evaluate whether the duration of scar evolution influences clinical, ultrasound, histological, and patient‐reported outcomes following microneedling treatment of linear atrophic scars. Methods: This was a post hoc analysis of a randomized controlled trial involving 24 patients with linear atrophic scars treated with microneedling. Scar maturation time was evaluated in relation to outcomes including erythema, hypopigmentation, hyperpigmentation, brightness, scar relief, and patient‐reported satisfaction. Evaluations were performed using standardized scales by dermatologists and self‐reported improvement. Paired t ‐tests were conducted to compare pre‐ and post‐treatment scores. The means of the deltas between pre‐ and post‐treatment values were compared across scar age strata (≤ 36 months vs. > 36 months, based on the median) using independent‐samples t ‐tests to assess whether scar age significantly influenced treatment response. Results: All clinical indicators showed statistically significant improvement following microneedling ( p < 0.05), regardless of scar age. There were no significant differences ( p > 0.05) in the mean deltas between the two scar age groups, suggesting that scar age did not significantly influence treatment response. Due to the exploratory nature of the study and the small sample size, uncorrected p ‐values were reported to avoid increasing Type II error, acknowledging an increased risk of false‐positive findings due to multiple comparisons. Conclusion: Within the parameters of this exploratory analysis, scar age did not significantly influence the clinical or patient‐reported response to microneedling in linear atrophic scars, suggesting that microneedling may be effective across different stages of scar maturation. However, larger prospective trials with extended follow‐up are warranted to validate these results and determine the optimal timing for intervention.

The number of newly developed substances with poor water solubility continually increases. Therefore, specialized formulation strategies are required to overcome the low bioavailability often associated with this property. This review provides an overview of novel physical modification strategies discussed in the literature over the past decades and focuses on oral dosage forms. A distinction is made between ‘brick-dust’ molecules, which are characterized by high melting points due to the solid-state properties of the substances, and ‘grease-ball’ molecules with high lipophilicity. In general, the discussed strategies are divided into the following three main categories: drug nanoparticles, solid dispersions, and lipid-based formulations.

In this review, we aim to highlight the advantages, challenges, and limitations of electronic tongues (e-tongues) in pharmaceutical drug development. The authors, therefore, critically evaluated the performance of e-tongues regarding their qualification to assess peroral formulations containing bitter active pharmaceutical ingredients. A literature search using the keywords ‘electronic’, ‘tongue’, ‘bitter’, and ‘drug’ in a Web of Science search was therefore initially conducted. Reviewing the publications of the past decade, and further literature where necessary, allowed the authors to discuss whether and how e-tongues perform as expected and whether they have the potential to become a standard tool in drug development. Specifically highlighted are the expectations an e-tongue should meet. Further, a brief insight into the technologies of the utilized e-tongues is given. Reliable protocols were found that enable (i) the qualified performance of e-tongue instruments from an analytical perspective, (ii) proper taste-masking assessments, and (iii) under certain circumstances, the evaluation of bitterness.

With facial aging, lower face suffers gravitational changes due to loss of skin elasticity and bone and cartilaginous tissues remodeling. If skin excess and sagging is not high enough to justify the surgical approach, the intervention with calcium hydroxyapatite is justifiable. The article describes a technique using calcium hydroxyapatite with lidocaine (CaHA; Radiesse+, Merz North America, Inc., Raleigh, NC, USA) injection in mandibula and chinto restore facial contour that was lost in aging. This case series included men and women who underwent Radiesse+ injection in the mandible and chin at a private clinic from June 2019 to January 2022. The sagging tissues in the jowls were repositioned, starting from an access in the jowl, with vectors directed to the mandible angle and chin. The product was deposited in the subcutaneous flat, in the form of a bolus and retro injection, along the mandible and chin region. The volume of product initially used was individualized based on individual needs, but due to local edema caused on the first day, patients were reassessed after 7-15 days, in order to obtain a satisfactory result, if necessary, more volume was applied.Results: Eighty-six patients were included. Mean scores on the Global Aesthetic Improvement Scale taken by patients 3 months after treatment indicated “much improved”. The procedure was well tolerated, with no adverse events. Restoring facial contour with collagen stimulation using a biostimulator such as Radiesse+, allows a natural and lasting result with a high degree of patient’s satisfaction and few adverse events.