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Since the discovery of magainins, cecropins and defensins 30 years ago, antimicrobial peptides (AMPs) have been hailed as a potential solution to the dearth of novel antibiotic development. AMPs have shown robust activity against a wide variety of pathogens, including drug-resistant bacteria. Unlike small-molecule antibiotics, however, AMPs have failed to translate this success to the clinic. Only the polymyxins, gramicidins, nisin and daptomycin are currently approved for medical use; the latter is the only example to have been developed in the last several decades. Nonetheless, researchers continue to isolate, modify and develop novel AMPs for therapeutic applications. Efforts have focused on increasing stability, reducing cytotoxicity, improving antimicrobial activity and incorporating AMPs in novel formulations, including nanoscale particles. As peptide synthesis and recombinant production methodologies improve, and more relevant bioassays become available, it becomes increasingly likely that AMPs will break the regulatory barrier and enter the marketplace as valuable antimicrobial weapons in the next 10 years.

PurposeSpray drying plays an important role in the pharmaceutical industry for product development of sensitive bio-pharmaceutical formulations. Process design, implementation and optimisation require in-depth knowledge of process-product interactions. Here, an integrated approach for the rapid, early-stage spray drying process development of trehalose and glucagon on lab-scale is presented.MethodsSingle droplet drying experiments were used to investigate the particle formation process. Process implementation was supported using in-line process analytical technology within a data acquisition framework recording temperature, humidity, pressure and feed rate. During process implementation, off-line product characterisation provided additional information on key product properties related to residual moisture, solid state structure, particle size/morphology and peptide fibrillation/degradation.ResultsA psychrometric process model allowed the identification of feasible operating conditions for spray drying trehalose, achieving high yields of up to 84.67%, and significantly reduced levels of residual moisture and particle agglomeration compared to product obtained during non-optimal drying. The process was further translated to produce powders of glucagon and glucagon-trehalose formulations with yields of >83.24%. Extensive peptide aggregation or degradation was not observed.ConclusionsThe presented data-driven process development concept can be applied to address future isolation problems on lab-scale and facilitate a systematic implementation of spray drying for the manufacturing of sensitive bio-pharmaceutical formulations.

Annealing is commonly used in traditional lyophilization processes to crystallize solutes, improve drying efficiency and reduce cake heterogeneity, yet its integration into continuous spin-freeze-drying has not yet been reported. This study investigates the effects of incorporating annealing into continuous spin-freeze-drying processes with a model peptide formulation. Contrary to expectations, annealing resulted in a compromised cake structure, including skin formation and extended drying times. In contrast, when annealing was not applied, an intact cake structure was observed. This was likely due to product temperatures exceeding the formulation's collapse threshold during primary drying. Further analysis suggested that specific formulation components contributed to these adverse outcomes, potentially due to phase separation. To mitigate such effects, a radiative cooling technology was implemented for continuous spin-freeze-drying to achieve precise temperature control and minimize background radiation during drying. While radiative cooling effectively maintained product temperatures below the collapse point, samples still displayed poor cake appearance and longer drying times when annealed compared to their non-annealed counterparts. Despite these issues, the peptide remained stable under all conditions. These findings highlight the necessity for careful process optimization when considering annealing and underscore the potential benefits of radiative cooling in improving product quality under certain conditions. Graphical Abstract

In recent years, the development of self-injectable formulations has attracted much attention, and the development of formulations to control pharmacokinetics, as well as drug release and migration in the skin, has become an active research area. In the present study, the development of a lipid-based depot formulation containing leuprorelin acetate (LA) as an easily metabolizable drug in the skin was prepared with a novel non-lamellar liquid-crystal-forming lipid of mono-O-(5,9,13-trimethyl-4-tetradecenyl) glycerol ester (MGE). Small-angle X-ray scattering, cryo-transmission electron microscopy, and nuclear magnetic resonance observations showed that the MGE-containing formulations had a face-centered cubic packed micellar structure. In addition, the bioavailability (BA) of LA after subcutaneous injection was significantly improved with the MGE-containing formulation compared with the administration of LA solution. Notably, higher Cmax and faster Tmax were obtained with the MGE-containing formulation, and the BA increased with increasing MGE content in the formulation, suggesting that LA migration into the systemic circulation and its stability might be enhanced by MGE. These results may support the development of self-administered formulations of peptide drugs as well as nucleic acids, which are easily metabolized in the skin.

Cathelicidins are a group of cationic, amphipathic peptides that play a vital role in the innate immune response of many vertebrates, including humans. Produced by immune and epithelial cells, they serve as natural defenses against a wide range of pathogens, including bacteria, viruses, and fungi. In humans, the cathelicidin LL-37 is essential for wound healing, maintaining skin barrier integrity, and combating infections. Cathelicidins of different origins have shown potential in treating various skin conditions, including melanoma, acne, and diabetic foot ulcers. Despite their promising therapeutic potential, cathelicidins face significant challenges in clinical application. Many peptide-based therapies have failed in clinical trials due to unclear efficacy and safety concerns. Additionally, the emergence of bacterial resistance, which contradicts initial claims of non-resistance, further complicates their development. To successfully translate cathelicidins into effective clinical treatments, therefore, several obstacles must be addressed, including a better understanding of their mechanisms of action, sustainable large-scale production, optimized formulations for drug delivery and stability, and strategies to overcome microbial resistance. This review examines the current knowledge of cathelicidins and their therapeutic applications and discusses the challenges that hinder their clinical use and must be overcome to fully exploit their potential in medicine.

Background: The skin microbiome plays a key role in maintaining skin health, and its composition can be influenced by cosmetic treatments. This study aimed to investigate the effects of SMART DNA Therapy treatment on facial skin microbiome composition, with specific focus on changes in commensal and pathogenic bacterial populations following multi-component anti-aging intervention. Methods: This clinical study included 10 Caucasian female participants aged 28–50 years (Clinical trial registration number: 0406/2023). Each participant received three Retix.C SMART DNA THERAPY treatments at 14-day intervals over 6 weeks. The protocol included three phases: chemical peeling with ferulic acid, peptide microinjections for DNA repair, and home-care products with antioxidants. Bacterial samples were collected from forehead and cheek skin before treatment and 2 weeks after the final treatment. Samples were analyzed using bacterial culture and PCR methods. Results: After treatment, the skin microbiome showed beneficial changes with increased numbers of helpful bacteria and elimination of harmful bacteria: complete removal of Cutibacterium acnes and Staphylococcus aureus was observed, Staphylococcus epidermidis and other beneficial bacteria increased on both forehead and cheek areas. Overall bacterial diversity decreased, and participants exhibited more similar microbiome patterns after treatment. Conclusions: SMART DNA Therapy treatment successfully modified the skin microbiome by increasing protective bacteria and eliminating pathogenic species. The treatment may support skin health through microbiome modulation and the potential antioxidant effects of its active ingredients, although these were not directly assessed in this study.

Pharmacologically active macromolecules, such as peptides, are still a major challenge in terms of designing a delivery system for their transport across absorption barriers and at the same time provide sufficiently high long-term stability. Spray freeze dried (SFD) lyospheres® are proposed here as an alternative for the preparation of fast dissolving porous particles for nasal administration of insulin. Insulin solutions containing mannitol and polyvinylpyrrolidone complemented with permeation enhancing excipients (sodium taurocholate or cyclodextrins) were sprayed into a cooled spray tower, followed by vacuum freeze drying. Final porous particles were highly spherical and mean diameters ranged from 190 to 250 µm, depending on the excipient composition. Based on the low density, lyospheres resulted in a nasal deposition rates of 90% or higher. When tested in vivo for their glycemic potential in rats, an insulin-taurocholate combination revealed a nasal bioavailability of insulin of 7.0 ± 2.8%. A complementary study with fluorescently labeled-dextrans of various molecular weights confirmed these observations, leading to nasal absorption ranging from 0.7 ± 0.3% (70 kDa) to 10.0 ± 3.1% (4 kDa). The low density facilitated nasal administration in general, while the high porosity ensured immediate dissolution of the particles. Additionally, due to their stability, lyospheres provide an extremely promising platform for nasal peptide delivery.

Purpose Therapeutic peptides generally exhibit poor oral bioavailability and require alternative methods of delivery. Implanted microelectromechanical systems-based multi-reservoir devices enable programmable, chronic, pulsatile peptide delivery. This report describes parathyroid hormone fragment (hPTH(1–34)) formulations suitable for delivery from a multi-reservoir array. Methods The stability of hPTH(1–34) lyophilizates obtained from aqueous acidic solutions was assessed by reverse phase high pressure liquid chromatography. An in vitro test device measured in vitro release kinetics. Results Novel, highly concentrated (>50 mg/mL) hPTH(1–34) solutions were dispensed as bulk samples (1–3 mg peptide) in vials and as individual doses (13–21 μg peptide) in reservoir arrays. Bulk and array samples were lyophilized and stored at 37°C. Bulk lyophilizate hPTH(1–34) purity after lyophilization, after 8 weeks, and after 26 weeks exceeded 96%, 90%, and 80%, respectively. The hPTH(1–34) stored in multi-reservoir arrays exhibited similar purity over 29 weeks at 37°C. Initially and over 29 weeks, over half of the peptide was consistently released from arrays into neutral, isotonic solution in less than 30 min with quantitative recoveries (>95%) within 3 h. Conclusions Clinically relevant formulations of hPTH(1–34) for use with implantable multi-reservoir devices are achievable.

To explore the application of short-peptide enteral nutrition formulation in mechanically ventilated pediatric patients with severe pneumonia and its impact on rehabilitation outcomes, providing practical clinical evidence for the nutritional support strategy in critically ill pneumonia children. This study retrospectively analyzed the clinical data of 90 neonatal pneumonia patients undergoing mechanical ventilation from May 2022 to December 2023. The patients were divided into an experimental group receiving short peptide enteral nutrition formulation via nasogastric tube and a control group receiving whole-protein enteral nutrition formulation via nasogastric tube. The nutritional risk was assessed using STRONGkids, and the nutritional status was analyzed through biochemical protein indicators. Additionally, mechanical ventilation time, hospitalization duration, incidence of ventilator-associated pneumonia (VAP), and disease outcomes were recorded and compared between the two groups. Both groups were assessed with medium to high nutritional risk, with no significant difference in the degree of nutritional risk (P > 0.05). After intervention, total protein, albumin, and prealbumin levels increased in both groups, with the experimental group showing significantly higher levels than the control group (P < 0.05). VAP predominantly occurred in the control group, with an incidence rate of 7% (3/45), showing a statistically significant difference between the two groups (P < 0.05). The experimental group exhibited significantly shorter Length of hospital stay and mechanical ventilation duration compared to the control group (P < 0.05). Moreover, there was no statistically significant difference in disease outcomes between the two groups (P > 0.05). Short peptide enteral nutrition formulation contributes to improving the treatment outcomes of mechanically ventilated pneumonia patients, providing a therapeutic approach for the nutritional support of critically ill children requiring mechanical ventilation.