Drug Delivery and Translational Research has published its second Inspirational Note
(this opens in a new tab). In this article, Robert Langer and Jeff Hrkach highlight the technological evolution of drug delivery from micro- to nano-, providing examples of approved medicines that demonstrate the significant impact of the drug delivery field in treating many diseases.
Read the featured article from the April 2020 issue! (this opens in a new tab)
Summary: Treatment of the neurological manifestations of lysosomal storage diseases remains an unmet medical need. BMN 250 is being developed as an enzyme replacement therapy administered directly into the brain ventricles via the intracerebroventricular (ICV) route for treating Sanfilippo type B. Patients with this rare neurological disease have deficient lysosomal alpha-N-acetylglucosaminidase (NAGLU) enzyme activity. Unlike the ICV route that readily provides biodistribution of therapy to target cells, we show in wild-type and disease animal models that intravenously-administered enzyme does not reach the target neuronal cells. The limited pharmacological response following intravenous administration is likely attributed to the clearance of substrate in endothelial cells that restrict biodistribution to target cells in the brain. Representative staining from superficial medulla oblongata from cynomolgus monkey received BMN 250 via the IV route shows that all NAGLU staining is co-localized with CD31-positive endothelial cells, indicating that IV administered NAGLU does not reach the target neurons. In contrast, NAGLU co-localizes with the neurons following ICV administration.
The Editorial Board of DDTR selected this article as the best paper of this issue.
Congratulations to the authors of Tumor growth inhibition by mSTEAP peptide nanovaccine inducing augmented CD8+ T cell immune responses (this opens in a new tab) for being awarded Paper of the Year by the CRS Nanomedicine and Nanoscale Delivery Focus Group.
Summary: TumOpen in Tabor antigen-specific cytotoxic T lymphocytes (CTL) directly play a critical role in immunologic tumor inhibition and eradication. To address whether peptide nanovaccine could enhance specific CTL response, we established a syngeneic prostate cancer mouse model with TRAMP-C2 cells, followed by the treatments with either mouse six-transmembrane epithelial antigen of the prostate （mSTEAP） peptides emulsified in incomplete Freund’s adjuvant (IFA) via subcutaneous (SC) injection or nanovaccine carrying an identical amount of mSTEAP peptides via IV or SC injection. Meanwhile, the mouse models were treated with either CD8b mAb followed by nanovaccine treatment, free mSTEAP peptide, or empty PLGA nanoparticles. Immune responses in these mice were examined using cytotoxicity assays at 14 days after treatment. Tumor size and survival in various treatment groups were measured and monitored. The results demonstrated that mSTEAP peptide nanovaccine resulted in tumor inhibition by eliciting a significantly stronger CD8+ T cell immune response when compared with the controls. Moreover, the survival periods of mice treated with mSTEAP nanovaccine were significantly longer than those of mice treated with mSTEAP peptide emulsified in IFA or the treatment controls.
This article will be free to access until May 11, 2020.
The Oral Drug Delivery Focus Group of the Controlled Release Society has awarded the 2019 Paper of the Year award to the paper by Desai et al., Loratadine self-microemulsifying drug delivery systems (SMEDDS) in combination with sulforaphane for the synergistic chemoprevention of pancreatic cancer (this opens in a new tab).
Summary: Pancreatic cancer remains refractory to current standards-of-care. Here, we first report that combination of a classical antihistaminic drug, Loratadine (LOR), and a neutraceutical compound, Sulforaphane (SFN), elicits remarkably synergistic chemo-preventive action on pancreatic cancer cells in vitro. However, LOR belongs to BCS class II exhibiting low solubility and high permeability that results in poor oral bioavailability. To address this limitation, we have developed a self-microemulsifying drug delivery system (SMEDDS) formulation carrying LOR, using Quality by Design approach (globule size, 95.13 ± 7.9 nm; PDI, 0.17 ± 0.04), and confirmed that this nanoformulation provides significantly enhanced dissolution profile of LOR in vitro. Further, the nanoformulation, in conjunction with SFN, provided in ~ 7-fold and ~ 11-fold reduction in IC50 values compared to free drug LOR-SFN combination in MIA PaCa-2 and Panc-1 cell lines, respectively. Hence, our studies successfully demonstrate that a unique low-dose combination of LOR encapsulated within SMEDDS with SFN shows significantly enhanced chemo-preventive efficacy in pancreatic cancer.
This paper will be free to access until May 5, 2020.
Drug Delivery and Translational Research has published its first Inspirational Note (this opens in a new tab). Inspirational Notes are short review articles covering the development of important medicines and medical devices. In this article, researchers from the Population Council highlight their experience in ethically bringing safe, effective, and acceptable contraceptive technologies to the world.
Congratulations to the authors of Depletion of collagen by losartan to improve tumor accumulation and therapeutic efficacy of photodynamic nanoplatforms (this opens in a new tab) for winning the DDTR Best Paper of the Year award for 2019.
Summary: It is critical to achieve efficient delivery of photosensitizers throughout the tumor sites in order to obtain therapeutically relevant photodynamic treatment (PDT) efficacy and desired clinical outcomes. However, synthesis and deposition of dense collagen in the tumor extracellular matrix (ECM) result in poor penetration and accumulation of photosensitizer within the tumor tissue. Herein, we develop a losartan pretreatment strategy to deplete tumor collagen, thereby improving the tumor accumulation and PDT efficacy of Chlorine 6 (Ce6) loaded periodic mesoporous organosilica (Ce6-PMO) photodynamic nanoplatform. After pretreatment with losartan in vivo, the tumor collagen I fraction in tumor tissue was significantly reduced by 53% and tumor uptake of Ce6-PMO subsequently administered via peritumoral and intravenous routes was remarkably enhanced. Further, combination of losartan and Ce6-PMO provided the best therapy efficacy, and the suppression rate of tumor volume was measured up to 82%. This study introduces a highly promising synergetic strategy to improve nanoplatform-based PDT efficacy for cancer therapy.
This paper will be free to access until April 27, 2020.
Galactomannan, a natural polymer, recognized to target macrophage mannose receptors, is reported to induce pro-inflammatory polarization in macrophages, suggesting its possible use as an anti-cancer agent. Hydrazinocurcumin, a pyrazole derivative of curcumin, is reported to exhibit increased anti-cancer efficacy over curcumin. Considering these facts, we synthesized self-assembled galactomannan nanoparticles containing hydrazinocurcumin (PSGM-HCNPs). These nanoparticles re-polarized IL-4 polarized macrophage cells from M2- to M1-like phenotype. Conditioned medium of re-polarized macrophages exhibited anti-metastatic potential and induced apoptosis in cancer cells. PSGM-HCNPs reduced tumor burden, increased survival time, decreased M2- and increased M1-like skewness among ascitic tumor-associated macrophages of tumor-bearing mice.
The Editorial Board of DDTR selected this article as the best paper of this issue.
The conference focuses on the design, synthesis and clinical validation of new drug delivery vehicles, and is designed to bridge the gap between basic science and unmet clinical needs with a particular focus on gene editing therapeutics, RNA therapeutics, sustained release technologies and immuno-engineering.
Optical poration poses an attractive therapeutic delivery modality for treating nail diseases, but the approach often accompanies collateral thermal damage to the surrounding nail tissue. In this paper, Raman/fluorescence microspectroscopy has been employed to better understand the mechanism of laser-mediated poration and thermal damage, which is instrumental to the optimization of nail poration and beyond.
The Editorial Board of DDTR selected this article as the best paper of this issue.
This article in the August 2019 Issue of Drug Delivery and Translational Research (DDTR) introduces a novel use of pore-forming microneedles, in combination with thermoresponsive hydrogels, for sustained transdermal drug delivery.
The Editorial Board of DDTR selected this article as the best paper of this issue.
