Dual Hypoxia-Targeting RNAi Nanomedicine for Precision Cancer Therapy.

As a hallmark of solid tumors, hypoxia promotes tumor growth, metastasis, and therapeutic resistance by regulating the expression of hypoxia-related genes. Hypoxia also represents a tumor-specific stimulus that has been exploited for the development of bioreductive prodrugs and advanced drug delivery systems. Cell division cycle 20 (CDC20) functions as an oncogene in tumorigenesis, and we demonstrated the significant upregulation of CDC20 mRNA in the tumor vs paratumor tissues of breast cancer patients and its positive correlation with tumor hypoxia.

Gellan Gum-Based Hydrogel for the Transdermal Delivery of Nebivolol: Optimization and Evaluation.

Poor solubility and appreciable first-pass metabolism have limited the oral bioavailability of nebivolol. The objective of the current investigation was to design, formulate, and optimize a hydrogel-based transdermal system for nebivolol using factorial design and compare its pharmacokinetics with oral suspension. Hydrogel formulations (F1-F8) were prepared by varying the amounts of gellan gum, carbopol, and polyethylene glycol.

Superiority of TPGS-loaded micelles in the brain delivery of vinpocetine via administration of thermosensitive intranasal gel.

Vinpocetine (VPN) is a synthetic derivative of the  alkaloids. The drug is characterized by a short half-life, limited water solubility and high hepatic first-pass effect. The objective was to develop different lipid-based nanocarriers (NCs) loaded into a thermosensitive in situ gelling (ISG) system to improve VPN bioavailability and brain targeting via intranasal (IN) delivery.

Chitosan-TPP nanoparticles stabilized by poloxamer for controlling the release and enhancing the bioavailability of doxazosin mesylate: , and evaluation.

Control the release and enhance the bioavailability of chitosan-doxazosin mesylate nanoparticles (DM-NPs). Improve DM bioavailability for the treatment of benign prostatic hyperplasia and hypertension. Plackett-Burman design was utilized to screen the variables affecting the quality of DM-NPs prepared by ionic gelation method.

Optimized vinpocetine-loaded vitamin E D-α-tocopherol polyethylene glycol 1000 succinate-alpha lipoic acid micelles as a potential transdermal drug delivery system: in vitro and ex vivo studies.

Background: Vinpocetine (VNP), a semisynthetic natural product, is used as a vasodilator for cerebrovascular and age-related memory disorders. VNP suffers from low oral bioavailability owing to its low water solubility and extensive first-pass metabolism. This work aimed at utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and alpha lipoic acid (ALA) to develop efficient micellar system for transdermal delivery of VNP.

Optimization of the Conditions for Plasmid DNA Delivery and Transfection with Self-Assembled Hyaluronic Acid-Based Nanoparticles.

Polymeric systems have been extensively studied as polyelectrolyte complexes to enhance the cellular delivery and transfection efficiency of genetic materials, such as plasmid DNA (pDNA). Here, self-assembled nanoparticles were formulated by complexation of hyaluronic acid (HA)-conjugated poly(ethylene glycol) (HA-PEG) and poly(ethylenimine) (HA-PEI), respectively, with pDNA creating relatively small, stable, and multifunctional nanoparticle complex formulations with high transfection efficiency. This formulation strategy offers high gene expression efficiency and negligible cytotoxicity in HeLa and A549 human lung cancer cell lines.

Glutathione-Responsive Prodrug Nanoparticles for Effective Drug Delivery and Cancer Therapy.

Spurred by recent progress in medicinal chemistry, numerous lead compounds have sprung up in the past few years, although the majority are hindered by hydrophobicity, which greatly challenges druggability. In an effort to assess the potential of platinum (Pt) candidates, the nanosizing approach to alter the pharmacology of hydrophobic Pt(IV) prodrugs in discovery and development settings is described. The construction of a self-assembled nanoparticle (NP) platform, composed of amphiphilic lipid-polyethylene glycol (PEG) for effective delivery of Pt(IV) prodrugs capable of resisting thiol-mediated detoxification through a glutathione (GSH)-exhausting effect, offers a promising route to synergistically improving safety and efficacy.

Development of optimized self-nanoemulsifying lyophilized tablets (SNELTs) to improve finasteride clinical pharmacokinetic behavior.

Objective: Preparation of an optimized finasteride (FSD) lyophilized tablets loaded with self-nanoemulsifying drug delivery system (SNEDDS).

Significance: Enhance FSD bioavailability in male pattern baldness and benign prostatic hyperplasia.

Methods: Two-step optimization was implemented to achieve the study goals.

Fabrication and evaluation of Phytomenadione as a nanostructure lipid carrier for enhancement of bioavailability.

Owing to its limited aqueous solubility, Phytomenadione (vitamin K) undergoes a low bioavailability (50%) with a large inter-individual variability after oral administration. Therefore, the aim of this work was to incorporate vitamin K into nanostructure lipid carrier systems to improve its aqueous solubility and bioavailability. Phytomenadione was used as a liquid lipid; Precirol ATO5, and Compritol ATO were used as solid lipids; Labrasol and Cremophore EL as water soluble surfactants; Capryol 90 and Lauroglycol as lipid soluble surfactants.

A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole.

Oral ketoconazole therapy is commonly associated with serious hepatotoxicity. Improving ocular drug delivery could be sufficient to treat eye fungal infections. The purpose of this study was to develop optimized ketoconazole poly(lactide-co-glycolide) nanoparticles (NPs) with subsequent loading into in situ gel (ISG) formulation for ophthalmic drug delivery.

Combined strategy for suppressing breast carcinoma MCF-7 cell lines by loading simvastatin on alpha lipoic acid nanoparticles.

Background: Augmentation of simvastatin (SMV) cytotoxicity in breast carcinoma cell lines MCF-7, by: improvement of cellular uptake and loading on alpha lipoic acid (ALA).

Methods: In this study, SMV was loaded on ALA nanoparticles and characterized for surface morphology, SMV entrapment efficiency percent (%EE), zeta potential and release profile. Cellular viability, morphology and uptake and DNA fragmentations were analyzed as a hallmark of cellular apoptosis.

Nicotinamide polymeric nanoemulsified systems: a quality-by-design case study for a sustained antimicrobial activity.

Nicotinamide, the amide form of vitamin B3, was demonstrated to combat some of the antibiotic-resistant infections that are increasingly common around the world. The objective of this study was to thoroughly understand the formulation and process variabilities affecting the preparation of nicotinamide-loaded polymeric nanoemulsified particles. The quality target product profile and critical quality attributes of the proposed product were presented.

Miconazole-loaded solid lipid nanoparticles: formulation and evaluation of a novel formula with high bioavailability and antifungal activity.

Background And Objective: Miconazole is a broad-spectrum antifungal drug that has poor aqueous solubility (<1 µg/mL); as a result, a reduction in its therapeutic efficacy has been reported. The aim of this study was to formulate and evaluate miconazole-loaded solid lipid nanoparticles (MN-SLNs) for oral administration to find an innovative way to alleviate the disadvantages associated with commercially available capsules.

Methods: MN-SLNs were prepared by hot homogenization/ultrasonication.

Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery.

Naturally occurring polymers, particularly of the polysaccharide type, have been used pharmaceutically for the delivery of a wide variety of therapeutic agents. Chitosan, the second abundant naturally occurring polysaccharide next to cellulose, is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of micro-as well as nanoparticles. The prepared particles have been exploited as a potential carrier for different therapeutic agents such as peptides, proteins, vaccines, DNA, and drugs for parenteral and nonparenteral administration.

Glycosylated Sertraline-Loaded Liposomes for Brain Targeting: QbD Study of Formulation Variabilities and Brain Transport.

Effectiveness of CNS-acting drugs depends on the localization, targeting, and capacity to be transported through the blood-brain barrier (BBB) which can be achieved by designing brain-targeting delivery vectors. Hence, the objective of this study was to screen the formulation and process variables affecting the performance of sertraline (Ser-HCl)-loaded pegylated and glycosylated liposomes. The prepared vectors were characterized for Ser-HCl entrapment, size, surface charge, release behavior, and in vitro transport through the BBB.

Transdermal glimepiride delivery system based on optimized ethosomal nano-vesicles: Preparation, characterization, in vitro, ex vivo and clinical evaluation.

This work aimed to develop an optimized ethosomal formulation of glimepiride then loading into transdermal films to offer lower drug side effect, extended release behavior and avoid first pass effect. Four formulation factors were optimized for their effects on vesicle size (Y1), entrapment efficiency (Y2) and vesicle flexibility (Y3). Optimum desirability was identified and, an optimized formulation was prepared, characterized and loaded into transdermal films.

Risperidone oral disintegrating mini-tablets: A robust-product for pediatrics.

This study was aimed at developing risperidone oral disintegrating mini-tablets (OD-mini-tablets) as age-appropriate formulations and to assess their suitability for infants and pediatric use. An experimental Box-Behnken design was applied to assure high quality of the OD-mini-tablets and reduce product variability. The design was employed to understand the influence of the critical excipient combinations on the production of OD-mini-tablets and thus guarantee the feasibility of obtaining products with dosage form uniformity.

Matrix-type transdermal films to enhance simvastatin ex vivo skin permeability.

This study aimed at employing Plackett-Burman design in screening formulation variables that affect quality of matrix-type simvastatin (SMV) transdermal film. To achieve this goal, 12 formulations were prepared by casting method. The investigated variables were Eudragit RL percentage, polymer mixture percentage, plasticizer type, plasticizer percentage, enhancer type, enhancer percentage and dichloromethane fraction in organic phase.

Utilization of nanotechnology to enhance percutaneous absorption of acyclovir in the treatment of herpes simplex viral infections.

This study aimed to formulate an optimized acyclovir (ACV) nanoemulsion hydrogel in order to provide a solution for the slow, variable, and incomplete oral drug absorption in patient suffering from herpes simplex viral infection. Solubility of ACV in different oils, surfactants, and cosurfactants was explored utilizing a cubic model mixture design to obtain a nanoemulsion with minimum globule size. Preparation of an optimized ACV nanoemulsion hydrogel using a three-factor, three-level Box-Behnken statistical design was conducted.

Taste-masked orodispersible tablets of cyclosporine self-nanoemulsion lyophilized with dry silica.

The aim of the current study was to investigate the effects of formulation parameters on the disintegration, water absorption and dissolution characteristics of cyclosporine A (CyA) loaded self-emulsifying drug delivery system (SEDDS) in an orodispersible compacts. Its taste masking efficiency was also attempted using an electronic tongue. ODTs were prepared by freeze-drying liquid SEDDS and synthetic amorphous silica suspension followed by direct compression.

Sildenafil citrate as oral solid lipid nanoparticles: a novel formula with higher bioavailability and sustained action for treatment of erectile dysfunction.

Objective: The aim of this study was to prepare sildenafil citrate as solid lipid nanoparticles (SLNs), in order to find an innovative way for alleviating the disadvantages associated with commercially available sildenafil citrate tablets. These limitations include poor solubility and extensive first-pass metabolism, resulting in low (40%) bioavailability and short elimination half-life (4 h).

Methods: SLNs were prepared by hot homogenization followed by ultrasonication.