Study on biopharmaceutics classification and oral bioavailability of a novel multikinase inhibitor NCE for cancer therapy.

Specific biopharmaceutics classification investigation and study on phamacokinetic profile of a novel drug candidate (2-methylcarbamoyl-4-{4-[3- (trifluoromethyl) benzamido] phenoxy} pyridinium 4-methylbenzenesulfonate monohydrate, NCE) were carried out. Equilibrium solubility and intrinsic dissolution rate (IDR) of NCE were estimated in different phosphate buffers. Effective intestinal permeability (P(eff)) of NCE was determined using single-pass intestinal perfusion technique in rat duodenum, jejunum and ileum at three concentrations.

Enhanced efficacy of combination therapy with adeno‑associated virus-delivered pigment epithelium-derived factor and cisplatin in a mouse model of Lewis lung carcinoma.

Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis, and the antitumor effect of adeno-associated virus (AAV)-mediated PEDF expression has been demonstrated in a range of animal models. The combined treatment of low-dose chemotherapy and gene therapy inhibits the growth of solid tumors more effectively than current traditional therapies or gene therapy alone. In the present study, the effect of treatment with an AAV2 vector harboring the human PEDF (hPEDF) gene in combination with low-dose cisplatin on the growth of Lewis lung carcinoma (LLC) in mice was assessed.

Prevention of postsurgical cauterization-induced peritoneal adhesions by biodegradable and thermosensitive micelles.

Postsurgical peritoneal adhesion is a major concern in clinical practice which causes significant morbidity and mortality. In this study, we investigated the efficacy of biodegradable and injectable thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) micelles in preventing postsurgical cauterization-induced peritoneal adhesion. The biodegradable PEG-PCL-PEG copolymer could form nano-sized micelles in water, which instantly turned into a non-flowing gel at body temperature due to micellar aggregation.

A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing.

A biodegradable in situ gel-forming controlled drug delivery system composed of curcumin loaded micelles and thermosensitive hydrogel was prepared and applied for cutaneous wound repair. Curcumin is believed to be a potent antioxidant and anti-inflammatory agent. Due to its high hydrophobicity, curcumin was encapsulated in polymeric micelles (Cur-M) with high drug loading and encapsulation efficiency.

Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature.

Purpose: Tumor associated macrophages (TAMs) are considered with the capacity to have both negative and positive effects on tumor growth. The prognostic value of TAM for survival in patients with solid tumor remains controversial.

Experimental Design: We conducted a meta-analysis of 55 studies (n = 8,692 patients) that evaluated the correlation between TAM (detected by immunohistochemistry) and clinical staging, overall survival (OS) and disease free survival (DFS).

Therapeutic application of injectable thermosensitive hydrogel in preventing local breast cancer recurrence and improving incision wound healing in a mouse model.

Many drug delivery systems (DDSs) have been investigated for local targeting of malignant disease with the intention of increasing anti-tumor activity and minimizing systemic toxicity. An injectable thermosensitive hydrogel was applied to prevent locoregional recurrence of 4T1 breast cancer in a mouse model. The presented hydrogel, which is based on poly(ethyleneglycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE), flows freely at normal temperature, forms a gel within seconds in situ at body temperature, and eventually releases the drug in a consistent and sustained fashion as it gradually biodegrades.

Novel vaccine adjuvant LPS-Hydrogel for truncated basic fibroblast growth factor to induce antitumor immunity.

The need to enhance the immunogenicity of tumor-associated antigens and modulate the resulting immune responses has prompted the development of new adjuvants. We prepared a novel adjuvant, lipopolysaccharides (LPS) loaded thermosensitive hydrogel (LPS-Hydrogel), for truncated basic fibroblast growth factor (tbFGF) peptide to enhance immunological responses and improve therapeutic effects in cancer. When co-formulated with tbFGF, LPS-Hydrogel formed antigen-adjuvant complexes, which enhanced antibody and cell-mediated responses in mice, thus promoting a more balanced antibody-mediated and cytotoxic T lymphocyte (CTL)-mediated immune response to inhibit tumor growth and metastases in vivo.

Polysorbate 80 coated poly (ɛ-caprolactone)-poly (ethylene glycol)-poly (ɛ-caprolactone) micelles for paclitaxel delivery.

In this article, polysorbate 80 coated poly (ɛ-caprolactone)-poly (ethylene glycol)-poly (ɛ-caprolactone) (PCEC) micelles were successfully prepared for paclitaxel (PTX) delivery. The particle size distribution, morphology, drug loading, encapsulation efficiency and sustained release profile of the micelles were studied in detail. The safety of the micelle formulation was evaluated by MTT assay on HEK293 cells.

AAV-mediated human PEDF inhibits tumor growth and metastasis in murine colorectal peritoneal carcinomatosis model.

Background: Angiogenesis plays an important role in tumor growth and metastasis, therefore antiangiogenic therapy was widely investigated as a promising approach for cancer therapy. Recently, pigment epithelium-derived factor (PEDF) has been shown to be the most potent inhibitor of angiogenesis. Adeno-associated virus (AAV) vectors have been intensively studied due to their wide tropisms, nonpathogenicity, and long-term transgene expression in vivo.

Pharmacokinetics and disposition of nanomedicine using biodegradable PEG/PCL polymers as drug carriers.

Micelles assembled from amphiphilic poly(ethylene glycol)/poly(-caprolactone) (PEG/PCL) copolymers are promised as safe and effective drug delivery systems. They offer the potential to achieve high solubility of hydrophobic drugs, long blood circulation time and effective delivery to target organs. These advantages contribute to their application as vehicles of a broad variation of therapeutic compounds.

Preventing postoperative abdominal adhesions in a rat model with PEG-PCL-PEG hydrogel.

Background: Poly (ethylene glycol)-poly (ɛ-caprolactone)-poly (ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel has been demonstrated to be biocompatible and thermosensitive. In this study, its potential efficacy and mechanisms of preventing postsurgical abdominal adhesions were investigated.

Results: PECE hydrogel was transformed into gel state from sol state in less than 20 seconds at 37°C.

Improving intraperitoneal chemotherapeutic effect and preventing postsurgical adhesions simultaneously with biodegradable micelles.

The two major concerns after cytoreductive surgery of abdominal and pelvic malignancies are residual tumors and peritoneal adhesions, which are inevitable and have great impact on prognosis. Therefore, to improve the intraperitoneal chemotherapeutic effect and prevent postsurgical adhesions simultaneously after surgery, we developed a novel strategy that combines the controlled drug delivery system (CDDS) with an antiadhesion barrier. Biodegradable poly(ethylene glycol)-poly(ɛ-caprolactone)-poly(ethylene glycol) (PECE) copolymer formed micelles in water, which turned instantly into a nonflowing gel at body temperature as a result of micellar aggregation.

Synthesis and characterization of injectable, thermosensitive, and biocompatible acellular bone matrix/poly(ethylene glycol)-poly (ε-caprolactone)-poly(ethylene glycol) hydrogel composite.

In orthopedic tissue engineering, the extensively applied acellular bone matrix (ABM) can seldom be prefabricated just right to mold the cavity of the diverse defects, might induce severe inflammation on account of the migration of small granules and usually bring the patients great pain in the treatment. In this study, a new injectable thermosensitive ABM/PECE composite with good biocompatibility was designed and prepared by adding the ABM granules into the triblock copolymer poly(ethylene eglycol)-poly(ε-caprolactone)-poly(ethylene eglycol) (PEG-PCL-PEG, PECE). The PECE was synthesized by ring-opening copolymerization and characterized by ¹H NMR.

A novel vaccine delivery system: biodegradable nanoparticles in thermosensitive hydrogel.

In this work, a novel vaccine delivery system, biodegradable nanoparticles (NPs) in thermosensitive hydrogel, was investigated. Human basic fibroblast growth factor (bFGF)-loaded NPs (bFGF-NPs) were prepared, and then bFGF-NPs were incorporated into thermosensitive hydrogel to form bFGF-NPs in a hydrogel composite (bFGF-NPs/hydrogel). bFGF-NPs/hydrogel was an injectable sol at ambient temperature, but was converted into a non-flowing gel at body temperature.

Prevention of abdominal adhesion formation by thermosensitive PECE-hydrogel in a rat uterine horn model.

In this work, we investigated the efficacy of PECE-hydrogel in preventing postsurgical peritoneal adhesions in the rat uterine horn model. Standardized surgical traumas were applied to the peritoneum of the abdominal wall and the uterine horns. PECE hydrogel was applied to the two wound surfaces.

Prevention of post-surgical abdominal adhesions by a novel biodegradable thermosensitive PECE hydrogel.

Background: Post-operative peritoneal adhesions are common and serious complications for modern medicine. We aim to prevent post-surgical adhesions using biodegradable and thermosensitive poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel. In this work, we investigated the effect of PECE hydrogel on preventing post-surgical abdominal adhesions in mouse and rat models.

Biodegradable self-assembled PEG-PCL-PEG micelles for hydrophobic honokiol delivery: I. Preparation and characterization.

This study aims to develop self-assembled poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) micelles to encapsulate hydrophobic honokiol (HK) in order to overcome its poor water solubility and to meet the requirement of intravenous administration. Honokiol loaded micelles (HK-micelles) were prepared by self-assembly of PECE copolymer in aqueous solution, triggered by its amphiphilic characteristic assisted by ultrasonication without any organic solvents, surfactants and vigorous stirring. The particle size of the prepared HK-micelles measured by Malvern laser particle size analyzer were 58 nm, which is small enough to be a candidate for an intravenous drug delivery system.

A novel composite drug delivery system: honokiol nanoparticles in thermosensitive hydrogel based on chitosan.

In this article, a novel composite drug delivery system, honokiol nanoparticles in biodegradable hydrogels based on chitosan (CS) and beta-glycerophosphate (beta-GP), was prepared. CS/beta-GP solution was liquid at room temperature and turned into gel as temperature increased. With increase in beta-GP concentration, the sol-gel transition temperature decreased accordingly.

Honokiol nanoparticles in thermosensitive hydrogel: therapeutic effects on malignant pleural effusion.

Honokiol (HK) can efficiently inhibit the growth of tumors. However, its clinical applications have been restricted by its extreme hydrophobicity. We hope to improve its water solubility by nanotechnology.

Biodegradable thermosensitive injectable PEG-PCL-PEG hydrogel for bFGF antigen delivery to improve humoral immunity.

In this contribution, a biodegradable and injectable thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel system was successfully prepared for basic fibroblastic growth factor (bFGF) antigen delivery. bFGF encapsulated PECE hydrogel system (bFGF-hydrogel) is an injectable free-flowing sol at ambient temperature, and forms a non-flowing gel at physiological temperature acting as antigen depot. Furthermore, the cytotoxicity results showed that the PECE hydrogel could be regarded as a safe carrier, and bFGF could be released from the hydrogel system in an extended period in vitro.

Toxicity evaluation of biodegradable and thermosensitive PEG-PCL-PEG hydrogel as a potential in situ sustained ophthalmic drug delivery system.

In this work, a biodegradable poly(ethylene glycol)-poly(epsilon-caprolactone)-poly (ethylene glycol) (PEG-PCL-PEG, PECE) triblock copolymer was successfully synthesized, which was flowing sol at low temperature and turned to nonflowing gel at body temperature. The toxicity evaluation of PECE hydrogel as a potential in situ sustained opthalmic drug delivery system was performed, including the biodegradability of PECE hydrogel in the eye, its effect on cultured human lens epithelia, intraocular pressure, and ocular tissues. The results indicated that the prepared PECE hydrogel was biocompatible and biodegradable despite of temporary elevated intraocular pressure and slight corneal endothelial damage at specific concentration.

Biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol) copolymers as drug delivery system.

Poly(epsilon-caprolactone)-poly(ethylene glycol) (PCL-PEG) copolymers are important synthetic biomedical materials with amphiphilicity, controlled biodegradability, and great biocompatibility. They have great potential application in the fields of nanotechnology, tissue engineering, pharmaceutics, and medicinal chemistry. This review introduced several aspects of PCL-PEG copolymers, including synthetic chemistry, PCL-PEG micro/nanoparticles, PCL-PEG hydrogels, and physicochemical and toxicological properties.

A novel poly(epsilon-caprolactone)-pluronic-poly(epsilon-caprolactone) grafted polyethyleneimine(PCFC-g-PEI), Part 1, synthesis, cytotoxicity, and in vitro transfection study.

Background: Polyethyleneimine (PEI), a cationic polymer, is one of the successful and widely used vectors for non-viral gene transfection in vitro. However, its in vivo application was greatly limited due to its high cytotoxicity and short duration of gene expression. To improve its biocompatibility and transfection efficiency, PEI has been modified with PEG, folic acid, and chloroquine in order to improve biocompatibility and enhance targeting.

Novel composite drug delivery system for honokiol delivery: self-assembled poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) micelles in thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) hydrogel.

This study aims to develop a novel composite drug delivery system (CDDS) for hydrophobic honokiol delivery: honokiol loaded micelles in thermosensitive hydrogel (honokiol micelles/hydrogel) based on biodegradable poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) copolymers. In our work, we found that PECE copolymers with different molecular weight and PEG/PCL ratios could be administered to form micelles or thermosensitive hydrogel, respectively. Honokiol loaded PECE micelles (honokiol micelles) were prepared by self-assembly of biodegradable PECE copolymer (PEG5000-PCL5000-PEG5000) triggered by its amphiphilic characteristic assisted by ultrasonication without using any organic solvents and surfactants.

Polymeric matrix for drug delivery: honokiol-loaded PCL-PEG-PCL nanoparticles in PEG-PCL-PEG thermosensitive hydrogel.

In this article, we demonstrated a novel injectable polymer matrix: honokiol (HK) loaded poly (epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) nanoparticles in thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel for the drug local delivery. First, HK, as a model hydrophobic drug, was loaded into PCL-PEG-PCL nanoparticles by emulsion solvent evaporation method to overcome its poor water solubility. Then, the HK-loaded PCEC nanoparticles (HK-PCEC) were incorporated into thermosensitive PEG-PCL-PEG hydrogel, which was sol at low temperature and could gel as a depot for sustained release of drug in situ after topical injection.