8 research outputs found
Immunomodulation effect of liposomal oxaliplatin
Immune modulation of the tumor microenvironment has been reported to participate in the therapeutic efficacy of many chemotherapeutic agents. Recently, we reported that liposomal encapsulation of oxaliplatin (l-OHP) within PEGylated liposomes conferred a superior antitumor efficacy to free l-OHP in murine colorectal carcinoma-bearing mice through permitting preferential accumulation of the encapsulated drug within tumor tissue. However, the contribution of the immune-modulatory properties of liposomal l-OHP and/or free l-OHP to the overall antitumor efficacy was not elucidated. In the present study, therefore, we investigated the effect of liposomal encapsulation of l-OHP within PEGylated liposomes on the antitumor immunity in both immunocompetent and immunodeficient mice. Liposomal l-OHP significantly suppressed the growth of tumors implanted in immunocompetent mice, but not in immunodeficient mice. In immunocompetent mice, liposomal l-OHP increased the tumor MHC-1 level and preserved antitumor immunity through decreasing the number of immune suppressor cells, including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages, which collectively suppress CD8+ T cell-mediated tumor cells killing. In contrast, free l-OHP ruined antitumor immunity. These results suggest that the antitumor efficacy of liposomal l-OHP is attributed, on the one hand, to its immunomodulatory effect on tumor immune microenvironment that is superior to that of free l-OHP, and on the other hand, to its direct cytotoxic effect on tumor cells
A Novel Strategy to Increase the Yield of Exosomes (Extracellular Vesicles) for an Expansion of Basic Research
Nasal absorption enhancement of protein drugs independent to their chemical properties in the presence of hyaluronic acid modified with tetraglycine-L-octaarginine
Biocompatible Polymers Modified with d‑Octaarginine as an Absorption Enhancer for Nasal Peptide Delivery
Peptide and protein
drugs, which are categorized as biologics,
exhibit poor membrane permeability. This pharmacokinetic disadvantage
has largely restricted the development of noninvasive dosage forms
of biologics that deliver into systemic circulation. We have been
investigating the potential use of cell-penetrating peptide-linked
polymers as a novel absorption enhancer to overcome this challenge.
Since our previous study revealed that biocompatible polyÂ(<i>N</i>-vinylacetamide-<i>co</i>-acrylic acid) modified
with d-octaarginine, a typical cell-penetrating peptide,
enhanced in vitro permeation of biomolecules such as plasmid DNA and
bovine serum albumin through cell membranes, the present study evaluated
whether the polymers enhanced in vivo absorption of biologics applied
on the mucosa. Mouse experiments demonstrated that d-octaarginine-linked
polymers drastically enhanced nasal absorption of exendin-4, whose
injection is clinically used. The mean bioavailability was 20% relative
to subcutaneous administration, even though it fell short of 1% when
exendin-4 alone was administered nasally. The absorption-enhancing
function of the polymers was superior to that of sodium caprate and
sodium <i>N</i>-(8-(2-hydroxybenzoyl)Âamino) caprylate, which
have been used for humans as an absorption enhancer. In vitro experiments
using several biologics with different characteristics revealed that
biologics interacted with d-octaarginine-linked polymers
and were taken up into cells when incubated with the polymers. The
interaction and cellular uptake were enhanced as molecular weights
of the biologics increased; however, their charge-dependent in vitro
performance was not clearly observed. The current data suggested that
biologics formulated with our polymers became an alternative to their
conventional invasive parenteral formulations