Purpose: Indocyanine green (ICG), a near infrared (NIR) dye clinically approved in medical diagnostics, possesses great heat conversion efficiency, which renders itself as an effective photosensitizer for photothermal therapy (PTT) of cancer. However, there remain bottleneck challenges for use in PTT, which are the poor photo and plasma stability of ICG. To address these problems, in this research, ICG-loaded silver nanoparticles were prepared and evaluated for the applicability as an effective agent for photothermal cancer therapy. Methods and Results: PEGylated bovine serum albumin (BSA)-coated silver core/shell nanoparticles were synthesized with a high loading of ICG (“PEG-BSA-AgNP/ICG”). Physical characterization was carried out using size analyzer, transmission electron microscopy, and Fourier transform infrared spectrophotometry to identify successful preparation and size stability. ICG-loading content and the photothermal conversion efficiency of the particles were confirmed with inductively coupled plasma mass spectrometry and laser instruments. In vitro studies showed that the PEG-BSA-AgNP/ICG could provide great photostability for ICG, and their applicability for PTT was verified from the cellular study results. Furthermore, when the PEG-BSA-AgNP/ICG were tested in vivo, study results exhibited that ICG could stably remain in the blood circulation for a markedly long period (plasma half-life: 112 min), and about 1.7% ID/g tissue could be accumulated in the tumor tissue at 4 h post-injection. Such nanoparticle accumulation in the tumor enabled tumor surface temperature to be risen to 50°C (required for photo-ablation) by laser irradiation and led to successful inhibition of tumor growth in the B16F10 s.c. syngeneic nude mice model, with minimal systemic toxicity. Conclusion: Our findings demonstrated that PEG-BSA-AgNPs could serve as effective carriers for delivering ICG to the tumor tissue with great stability and safety.

The development of oral tablet formulation for herbal medicines has been restricted by large drug loadings and the poor physicochemical and mechanical properties of dry herbal extracts (DHEs). Herein, statistical experimental designs were applied to herbal tablet formulation development and optimization using Wuzi Yanzong dry extract (WYE). The tablet disintegration time and hardness were identified as the critical quality attributes (CQAs) of the product. The tablet formulation was designed to achieve a high drug loading (50% or higher of WYE), shorter tablet disintegration time (less than 30 minutes), and suitable hardness (6.0 to 7.5 kp). A D-optimal mixture design was used to evaluate the effects of excipients on CQAs to minimize the risk compression failure and improve the tabletability in formulations containing WYE at 50% and 65% by weight. A partial least squares model was used to elucidate the multivariate relationships between a large number of formulation variables and product CQAs, and determine the maximum possible WYE loading. From overlaid plots of the effects of formulation variables on CQAs, it was found that a maximum WYE loading of 67% in tablet formulation satisfied the acceptance criteria of CQAs. In conclusion, this study shows that multivariate statistical tools are useful for developing tablet formulations containing high doses of herbal extracts and establishing control strategies that ensure product quality.

Toxin peptides derived from the skin secretions of amphibians possess unique hypoglycemic activities. Many of these peptides share cationic and amphipathic structural similarities and appear to possess cell-penetrating abilities. The mechanism of their insulinotropic action is yet not elucidated, but they have shown great potential in regulating the blood glucose levels in animal models. Therefore, they have emerged as potential drug candidates as therapeutics for type 2 diabetes. Despite their anti-diabetic activity, there remain pharmaceutical challenges to be addressed for their clinical applications. Here, we present an overview of recent studies related to the toxin-derived anti-diabetic peptides derived from the skin secretions of amphibians. In the latter part, we introduce the bottleneck challenges for their delivery in vivo and general drug delivery strategies that may be applicable to extend their blood circulation time. We focus our research on the strategies that have been successfully applied to improve the plasma half-life of exendin-4, a clinically available toxin-derived anti-diabetic peptide drug.

Protein drugs have been emerging as a class of promising therapeutics. However, their topical application has been limited by their high molecular weight and poor permeability to the cell membrane. In this study, we aimed to enhance human growth hormone (hGH) permeability for topical application by conjugation of TAT peptide, a cell-penetrating peptide, to hGH via crosslinker. After TAT was conjugated to hGH, TAT-hGH was purified by affinity chromatography. TAT-hGH significantly increased cell proliferation compared with the control. Interestingly, the effect of TAT-hGH was higher than hGH at the same concentration. Furthermore, the conjugation of TAT to hGH enhanced the permeability of TAT-hGH across the cell membrane without affecting its biological activity in vitro. In vivo, the topical application of TAT-hGH into scar tissue markedly accelerated wound healing. Histological results showed that TAT-hGH dramatically promoted the re-epithelialization of wounds in the initial stage. These results demonstrate TAT-hGH as a new therapeutic potential drug for wound healing treatment. This study also provides a new method for topical protein application via enhancement of their permeability.

Introduction: Extensive research has focused on identifying effective treatments for NAFLD, with numerous bioactive peptide candidates showing significant promise. In this research, a long-acting esculentin-2CHa(1-30)-coated AuNPs (ESC-ABD-AuNPs) was developed and the applicability was evaluated for their use in the treatment of non-alcoholic fatty liver disease (NAFLD). Methods: ESC-ABD-AuNPs were synthesized by adopting a 1-step reduction process and the successful preparation of the nanoparticles (NPs) was assessed by various physical characterizations including transmission electron microscopy (TEM), ultraviolet-visible (UV-VIS) absorption spectra, dynamic light scattering (DLS), and Fourier Transform Infrared Spectroscopy (FT-IR). After the ESC-ABD-AuNPs were prepared, cytotoxicity, pharmacokinetics (PK), and biodistribution profiles were identified. Then, with a high-fat diet (HFD)-fed obese mice model, efficacy studies were carried out focused on their effects for anti-hyperglycemia and anti-NAFLD. Furthermore, the feasibility of loading a small molecule onto the NPs was evaluated for potential combination therapy. Results: ESC-ABD-AuNPs were synthesized with an average hydrodynamic size of 120 (± 10) nm and demonstrated good stability and an extended plasma half-life of 28.3 h. The NPs exhibited high liver accumulation and were well tolerated in cell viability tests. In PK and biodistribution studies, ESC-ABD-AuNPs showed prolonged retention in major organs, such as the pancreas and the liver. Therapeutic efficacy was demonstrated in the HFD-fed obese mice, where the ESC-ABD-AuNPs significantly reduced blood glucose levels, improved glucose tolerance, and mitigated liver fat accumulation. The ESC-ABD-AuNPs platform also showed potential for combination therapies, demonstrated by its ability to load obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, found effective for the treatment of NAFLD in clinical studies. Conclusion: Overall, this study has demonstrated the promising potential of ESC-ABD-AuNPs as a novel treatment for NAFLD. This research suggests that ESC-ABD-AuNPs could be a significant advancement in drug delivery and liver disease treatment, particularly for combination therapies.