"Felodipine-indomethacin" co-amorphous supersaturating drug delivery systems: "Spring-parachute" process, stability, in vivo bioavailability, and underlying molecular mechanisms.

Amorphous solid dispersions (ASD) are one of most commonly used supersaturating drug delivery systems (SDDS) to formulate insoluble active pharmaceutical ingredients. However, the development of polymer-guided stabilization of ASD systems faces many obstacles. To overcome these shortcomings, co-amorphous supersaturable formulations have emerged as an alternative formulation strategy for poorly soluble compounds.

Interfacial properties and micellization of triblock poly(ethylene glycol)-poly(-caprolactone)-polyethyleneimine copolymers.

This study aimed to explore the link between block copolymers' interfacial properties and nanoscale carrier formation and found out the influence of length ratio on these characters to optimize drug delivery system. A library of diblock copolymers of PEG-PCL and triblock copolymers with additional PEI (PEG-PCL-PEI) were synthesized. Subsequently, a systematic isothermal investigation was performed to explore molecular arrangements of copolymers at air/water interface.

Hot melt extrusion technology for improved dissolution, solubility and "spring-parachute" processes of amorphous self-micellizing solid dispersions containing BCS II drugs indomethacin and fenofibrate: Profiles and mechanisms.

Many strategies have been employed to improve oral drug delivery. One such approach involves the use of supersaturable delivery systems such as amorphous self-micellizing solid dispersions (SmSDs). SmSDs have attracted more attention recently, but little is known regarding the impact of production methods on profiles and internal mechanisms of final SmSDs in spite of its importance.

The Influence of Cellulosic Polymer's Variables on Dissolution/Solubility of Amorphous Felodipine and Crystallization Inhibition from a Supersaturated State.

The collective impact of cellulosic polymers on the dissolution, solubility, and crystallization inhibition of amorphous active pharmaceutical ingredients (APIs) is still far from being adequately understood. The goal of this research was to explore the influence of cellulosic polymers and incubation conditions on enhancement of solubility and dissolution of amorphous felodipine, while inhibiting crystallization of the drug from a supersaturated state. Variables, including cellulosic polymer type, amount, ionic strength, and viscosity, were evaluated for effects on API dissolution/solubility and crystallization processes.

Enhancing solid tumor therapy with sequential delivery of dexamethasone and docetaxel engineered in a single carrier to overcome stromal resistance to drug delivery.

Nanomedicines are often designed to target and treat solid tumors. Unfortunately, tumor and stroma composed of dense extracellular matrix, abnormal vascular barriers, elevated interstitial fluid pressure, et al., which impede the access and accumulation of nanomedicines into tumors.

Prior anti-CAFs break down the CAFs barrier and improve accumulation of docetaxel micelles in tumor.

Background: Abnormal expression of stromal cells and extracellular matrix in tumor stroma creates a tight barrier, leading to insufficient extravasation and penetration of therapeutic agents. Cancer-associated fibroblasts (CAFs) take on pivotal roles encouraging tumor progression.

Method: To surmount the refractoriness of stroma, we constructed a multi-targeting combined scenario of anti-CAFs agent tranilast and antitumor agent docetaxel micelles (DTX-Ms).

Deepened cellular/subcellular interface penetration and enhanced antitumor efficacy of cyclic peptidic ligand-decorated accelerating active targeted nanomedicines.

Introduction: Acceleration and improvement of penetration across cell-membrane interfaces of active targeted nanotherapeutics into tumor cells would improve tumor-therapy efficacy by overcoming the issue of poor drug penetration. Cell-penetrating peptides, especially synthetic polyarginine, have shown promise in facilitating cargo delivery. However, it is unknown whether polyarginine can work to overcome the membrane interface in an inserted pattern for cyclic peptide ligand-mediated active targeting drug delivery.

Self-micellizing solid dispersions enhance the properties and therapeutic potential of fenofibrate: Advantages, profiles and mechanisms.

The goal of this work was to compare fenofibrate (FEN)-containing self-micellizing solid dispersion (SmSD) and non-self-micellizing solid dispersion (NsSD) systems. Exploration of underlying mechanisms to improve FEN dissolution/solubility profiles was conducted to understand the enhanced therapeutic potential. SmSD and NsSD of FEN systems (SmSD/FEN and NsSD/FEN) were fabricated using a fuse-quench cooling method.

Treating metastatic triple negative breast cancer with CD44/neuropilin dual molecular targets of multifunctional nanoparticles.

Metastasis of cancer makes up the vast majority of cancer-related deaths, and it usually initiates from tumor cells invasiveness and develops through tumor neovasculature. In this work, we have fabricated a CD44/neuropilin dual receptor-targeting nanoparticulate system (tLyP-1-HT NPs) with endogenous or FDA approved components for treating metastatic triple negative breast cancer (TNBC). The enhanced specific targeting of tLyP-1-HT NPs to both metastatic tumor cells and metastasis-supporting tumor neovasculature was contributed by means of CD44/neuropilin dual receptor-mediated interaction.

Combination therapy with micellarized cyclopamine and temozolomide attenuate glioblastoma growth through Gli1 down-regulation.

Glioblastoma multiforme (GBM) is the most common and deadly brain cancer, characterized by its aggressive proliferation to adjacent tissue and high recurrence rate. We studied the efficacy and related mechanisms of the combination of cyclopamine (Cyp, a Sonic-hedgehog pathway (Shh) inhibitor) and temozolomide (TMZ, the clinically most used chemotherapeutic agent) in anti-GBM treatment. The micellarized Cyp (MCyp) showed better performance than Cyp solution in inhibiting GBM cells proliferation (3.

On the inherent properties of Soluplus and its application in ibuprofen solid dispersions generated by microwave-quench cooling technology.

Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, or Soluplus, is a relatively new copolymer and a promising carrier of amorphous solid dispersions. Knowledge on the inherent properties of Soluplus (e.g.

[Activatable cell-penetrating peptides: a potential activatable modality for diseases diagnosis and therapy].

Cell-penetrating peptides are composed of positively-charged amino acids that can mediate molecules or nano-carriers across cell membranes. However, most of the known cell-penetrating peptides have no cell- or tissue-specificity, with affinity to almost all types of cells in internalization. The non-specificity of cell-penetrating peptides is a significant obstacle in the application to targeted delivery of imaging probes and therapeutic agents.

[Rules and characteristics of crystallization inhibition of cellulose polymers against drugs in supersaturated states].

This study aims to explore the characteristics of crystallization inhibition by cellulose polymers at the supersaturated states of drugs. The study was performed by simulating supersaturated process and preparing supersaturated drug solid, and was carried out by measuring the content of drugs at different time points using dissolution apparatus. The types, amounts, ionic intensity and viscosity of cellulose polymers were examined to assess the crystallization inhibition effect on BCS II class drug indomethacin.

Tumor-specific penetrating peptides-functionalized hyaluronic acid-d-α-tocopheryl succinate based nanoparticles for multi-task delivery to invasive cancers.

Poor site-specific delivery and incapable deep-penetration into tumor are the intrinsic limitations to successful chemotherapy. Here, the tumor-homing penetrating peptide tLyP-1-functionalized nanoparticles (tLPTS/HATS NPs), composed of two modularized amphiphilic conjugates of tLyP-1-PEG-TOS (tLPTS) and TOS-grafted hyaluronic acid (HATS), had been fabricated for tumor-targeted delivery of docetaxel (DTX). The prepared tLPTS/HATS NPs had about 110 nm in mean diameter, high drug encapsulation efficiency (93%), and sustained drug release behavior.

[The application of enzyme-sensitive activatable cell-penetrating peptides to targeted delivery system].

Cell-penetrating peptides (CPPs) offer a non-selective and receptor-independent mode to promote cellular uptake. Although the non-specificity of CPP-mediated internalization allows this approach applicable to a wide range of tumor types potentially, their universality is a significant obstacle to their clinical utility for targeted delivery of cancer therapeutics and imaging agents. Accordingly, many reports have focused on selective switching of systemically delivered inert CPPs into their active form in lesions (tumor).

Enhance Cancer Cell Recognition and Overcome Drug Resistance Using Hyaluronic Acid and α-Tocopheryl Succinate Based Multifunctional Nanoparticles.

Multidrug resistance (MDR) presents a clinical obstacle to cancer chemotherapy. The main purpose of this study was to evaluate the potential of a hyaluronic acid (HA) and α-tocopheryl succinate (α-TOS) based nanoparticle to enhance cancer cell recognition and overcome MDR, and to explore the underlying mechanisms. A multifunctional nanoparticle, HTTP-50 NP, consisted of HA-α-TOS (HT) conjugate and d-α-tocopheryl polyethylene glycol succinate (TPGS) with docetaxel loaded in its hydrophobic core.

Roles of ligand and TPGS of micelles in regulating internalization, penetration and accumulation against sensitive or resistant tumor and therapy for multidrug resistant tumors.

There are several obstacles in the process of successful treatment of malignant tumors, including toxicity to normal cells, inefficiency of drug permeation and accumulation into the deep tissue of solid tumor, and multidrug resistance (MDR). In this work, we prepared docetaxel (DTX)-loaded hybrid micelles with DSPE-PEG and TPGS (TPGS/DTX-M), where TPGS serves as an effective P-gp inhibitor for overcoming MDR, and active targeting hybrid micelles (FA@TPGS/DTX-M) with targeting ligand of folate on the hybrid micelles surface offering active targeting to folate receptor-overexpressed tumor cells. A systematic comparative evaluation of these micelles on cellular internalization, sub-cellular distribution, antiproliferation, mitochondrial membrane potential, cell apoptosis and cell cycle, permeation and inhibition on 3-dimensional multicellular tumor spheroids, as well as antitumor efficacy and safety assay in vivo were well performed between sensitive KB tumors and resistant KBv tumors, and among P-gp substrate or not.

Therapeutic potential of targeted multifunctional nanocomplex co-delivery of siRNA and low-dose doxorubicin in breast cancer.

Malignant tumors remain a major health burden throughout the world, and effective therapeutic strategies are urgently needed. Combining gene therapy with chemotherapeutics in a single delivery system is more effective than co-treatment of cancer with individual delivery systems carrying either gene or drug. In this study, a multifunctional folate-decorated and pH-responsive PHD/PPF/siVEGF nanocomplex is developed via a self-assembly process utilizing ternary pre-functionalized polymers with vascular endothelial growth factor targeted siRNA.