Targeting prostate cancer with docetaxel-loaded peptide 563-conjugated PEtOx-co-PEI-b-PCL polymeric micelle nanocarriers.

Prostate cancer is a global disease that negatively affects the quality of life. Although various strategies against prostate cancer have been developed, only a few achieved tumor-specific targeting. Therefore, a special emphasis has been placed on the treatment of cancer using nano-carrier-encapsulated chemotherapeutic agents conjugated with tumor-homing peptides.

Cell culture and pharmacokinetic evaluation of a solid dosage formulation containing a water-insoluble orphan drug manufactured by FDM-3DP technology.

The in-vitro cytotoxicity, in-vitro permeability and in-vivo pharmacokinetics of a BCS Class-II drug - rufinamide - in a 3DP tablet formulation were evaluated. The cytotoxicity of the 3DP tablet formulation was evaluated with an MTT test; in-vitro permeability was evaluated with a Caco-2 cell culture study; and in-vivo pharmacokinetics were evaluated in Wistar albino male rats. The pharmacokinetic studies were performed following a two-sequence and single-period design approach.

The Nanosuspension Formulations of Daidzein: Preparation and Characterization.

Objectives: Daidzein (DZ), a water-insoluble isoflavone, has many beneficial effects (anti-inflammatory, antioxidant, and anticancer effects, etc.) on human health. DZ has a very low oral bioavailability related to its physicochemical properties (low solubility, intense metabolism of DZ in the intestine and liver).

Formulation and Evaluation of Telmisartan Nanoparticles Prepared by Emulsion-Solvent Evaporation Technique.

Objectives: Telmisartan (TLM) is an antihypertensive drug that has been shown to have antiproliferative effects on cancer cells. It has low solubility and suboptimal oral bioavailability. To investigate the potential anticancer effect of TLM on breast cancer cells, poly (D, L-lactide) (PLA) nanoparticles were formulated with the benefit of improving its solubility.

Development and characterization of pullulan-based orally disintegrating films containing amlodipine besylate.

The aim of this study was to prepare pullulan-based orally disintegrating films (ODFs) containing amlodipine besylate, an anti-hypertensive drug, by the solvent casting method. For this purpose, nine different ODF formulations (F1-F9) were prepared by using different plasticizers (glycerol, sorbitol, propylene glycol) and different superdisintegrants (croscarmellose sodium, sodium starch glycolate, crospovidone). FD&C Green and aspartame were used as coloring agent and sweetener, respectively.

Exploiting ionisable nature of PEtOx--PEI to prepare pH sensitive, doxorubicin-loaded micelles.

Aims: This study was conducted to evaluate block copolymers containing two different poly(ethyleneimine) (PEI) amounts, as new pH-sensitive micellar delivery systems for doxorubicin.

Methods: Micelles were prepared with block copolymers consisting of poly(2-ethyl-2-oxazoline)--poly(ethyleneimine) (PEtOx--PEI) and poly(ε-caprolactone) (PCL) as hydrophilic and hydrophobic blocks, respectively. Doxorubicin loading, micelle size, pH-dependent drug release, and in vitro cytotoxicity on MCF-7 cells were investigated.

Design of ocular drug delivery platforms and in vitro - in vivo evaluation of riboflavin to the cornea by non-interventional (epi-on) technique for keratoconus treatment.

Aim: Keratoconus is a common and progressive eye disease characterized by thinning and tapering of the cornea. This degenerative eye disease is currently treated in the clinic with an interventional technique ("epi-off") that can cause serious side effects as a result of the surgical procedure. The aim of this project is to design innovative formulations for the development of a riboflavin-containing medicinal product to develop a non-invasive ("epi-on") keratoconus treatment as an alternative to current treatment modalities.

Development of an Anti-Inflammatory Drug-Incorporated Biomimetic Scaffold for Corneal Tissue Engineering.

The aim of this study was to design naproxen sodium (NS)-containing, biomimetic, porous poly(lactide--glycolide) (PLGA) scaffolds for regeneration of damaged corneal epithelium. NS-incorporated PLGA scaffolds were prepared using the emulsion freeze-drying method and then coated with collagen or poly-l-lysine. Porosity measurements of the scaffolds were performed by the gas adsorption/desorption method and the scaffolds demonstrated highly porous, open-cellular pore structures with pore sizes from 150 to 200 μm.

Combination of Paclitaxel and R-flurbiprofen loaded PLGA nanoparticles suppresses glioblastoma growth on systemic administration.

Malignant gliomas are highly lethal. Delivering chemotherapeutic drugs to the brain in sufficient concentration is the major limitation in their treatment due to the blood-brain barrier (BBB). Drug delivery systems may overcome this limitation and can improve the transportation through the BBB.

Preparation, characterization and pharmacokinetic evaluation of rosuvastatin calcium incorporated cyclodextrin-polyanhydride nanoparticles.

The aim of the study was to formulate, cyclodextrin (CD)-polyanhydride (PA) nanoparticles (CPNs) with rosuvastatin calcium (RCa) in order to enhance the poor oral bioavailability. CPNs containing RCa/CD complexes were prepared by a modified solvent displacement method and morphological analyses, particle size (PS), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), DSC, FT-IR, XRD, H-NMR analyses were performed. release properties, release kinetics, cytotoxicity, permeability and pharmacokinetic studies were also studied.

Development of novel self-assembled polymeric micelles from partially hydrolysed poly(2-ethyl-2-oxazoline)-co-PEI-b-PCL block copolymer as non-viral vectors for plasmid DNA in vitro transfection.

A new efficient, non-viral gene delivery cationic polymeric micellar system was developed by partial hydrolysis of poly(2-ethyl-2-oxazoline) (PEtOx) with two different hydrolysis percentages of PEtOx (30% and 60%) to reduce the disadvantages of the PEI. These self-assemble amphiphilic cationic micelles prepared from poly(2-ethyl-2-oxazoline)-co-poly(ethyleneimine)-block-poly(ɛ-caprolactone) (PEtOx-co-PEI-b-PCL) (PPP30) and poly(2-ethyl-2-oxazoline) -co-poly(ethyleneimine)-block-poly(ɛ-caprolactone) (PEtOx-co-PEI-b-PCL) (PPP60) block copolymers were successfully condensed with pEGFP-C3 plasmid DNA via electrostatic interactions to form micelle/DNA complexes with desirable particle sizes. All formulations showed low critical micelle concentration (CMC) values that means highly stable in serum containing medium.

A potential non-invasive glioblastoma treatment: Nose-to-brain delivery of farnesylthiosalicylic acid incorporated hybrid nanoparticles.

New drug delivery systems are highly needed in research and clinical area to effectively treat gliomas by reaching a high antineoplastic drug concentration at the target site without damaging healthy tissues. Intranasal (IN) administration, an alternative route for non-invasive drug delivery to the brain, bypasses the blood-brain-barrier (BBB) and eliminates systemic side effects. This study evaluated the antitumor efficacy of farnesylthiosalicylic acid (FTA) loaded (lipid-cationic) lipid-PEG-PLGA hybrid nanoparticles (HNPs) after IN application in rats.

Farnesylthiosalicylic acid-loaded lipid-polyethylene glycol-polymer hybrid nanoparticles for treatment of glioblastoma.

Objectives: We aimed to develop lipid-polyethylene glycol (PEG)-polymer hybrid nanoparticles, which have high affinity to tumour tissue with active ingredient, a new generation antineoplastic drug, farnesylthiosalicylic acid (FTA) for treatment of glioblastoma.

Method: Farnesylthiosalicylic acid-loaded poly(lactic-co-glycolic acid)-1,2 distearoyl-glycerol-3-phospho-ethanolamine-N [methoxy (PEG)-2000] ammonium salt (PLGA-DSPE-PEG) with or without 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) hybrid nanoparticles has been prepared and evaluated for in-vitro characterization. Cytotoxicity of FTA-loaded nanoparticles along with its efficacy on rat glioma-2 (RG2) cells was also evaluated both in vitro (in comparison with non-malignant cell line, L929) and in vivo.

Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a mucolytic agent for cystic fibrosis patients.

Objective: This study aimed to design and characterize an inhalable dry powder of ciprofloxacin or levofloxacin combined with the mucolytics acetylcysteine and dornase alfa for the management of pulmonary infections in patients with cystic fibrosis.

Methods: Ball milling, homogenization in isopropyl alcohol and spray drying processes were used to prepare dry powders for inhalation. Physico-chemical characteristics of the dry powders were assessed via thermogravimetric analysis, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry and scanning electron microscopy.

Development and evaluation of orally disintegrating tablets comprising taste-masked mirtazapine granules.

Introduction: Orally disintegrating tablets (ODTs) provide an important treatment option for pediatric, geriatric and psychiatric patients. In our previous study, we have performed the initial studies for the formulation development and characterization of new ODT formulations containing a bitter taste drug, mirtazapine, coated with 6% (w/w) Eudragit E-100 (first group of formulations, FGF) without taste evaluation. In present study, coating ratio of the drug was increased to 8% (w/w) (second group of formulations, SGF) to examine the effect of increased coating ratio of drug on in vitro characterization of the formulations including in vitro taste masking study.

New azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies.

Azole antifungals are potent inhibitors of fungal lanosterol 14α demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design, synthesis, and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations.

Design and In Vitro Evaluation of Bispecific Complexes and Drug Conjugates of Anticancer Peptide, LyP-1 in Human Breast Cancer.

Purpose: LyP-1, a nine-amino-acid tumor homing peptide, selectively binds to its cognate receptor, p32. Overexpression of p32 in certain tumors should allow use of LyP-1 as a targeting agent for the delivery of therapeutic or diagnostic agents. Peptide conjugates are developed for enhanced pre-targeting of MDA-MB-231 breast cancer cells with peptide-antibody bispecific complexes and targeting with multiple-drug/-fluorophore-conjugated nano-polymers.

Dexamethasone - PAMAM dendrimer conjugates for retinal delivery: preparation, characterization and in vivo evaluation.

Objective: Ocular diseases affecting retina, such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and glaucoma are the major causes of blindness, and their treatment is still a challenge due to the special structure of the eye. The purpose of this study was to prepare a sustained release DEX conjugate formulation with enhanced ocular permeation using poly(amidoamine) (PAMAM) dendrimers and to evaluate the effects of conjugation on DEX release and ocular residence time.

Methods: PAMAM G3.

Lysozyme-loaded lipid-polymer hybrid nanoparticles: preparation, characterization and colloidal stability evaluation.

Context: Lipid-polymer hybrid nanoparticles (LPNPs) are polymeric nanoparticles enveloped by lipid layers, which have emerged as a potent therapeutic nanocarrier alternative to liposomes and polymeric nanoparticles.

Objective: The aim of this work was to develop, characterize and evaluate LPNPs to deliver a model protein, lysozyme.

Materials And Methods: Lysozyme-loaded LPNPs were prepared by using the modified w/o/w double-emulsion-solvent-evaporation method.

In Vitro/In Vivo Evaluation of Dexamethasone--PAMAM Dendrimer Complexes for Retinal Drug Delivery.

Current treatment options for diabetic retinopathy (DR) have side effects because of invasive application and topical application does not generally result in therapeutic levels in the target tissue. Therefore, improving the drug delivery to retina, following topical administration, might be a solution to DR treatment problems. The purpose of this study was to investigate the complexation effects of poly(amidoamine) (PAMAM) dendrimers on ocular absorption of dexamethasone (DEX).

Preparation and in vitro/in vivo evaluation of cyclosporin A-loaded nanodecorated ocular implants for subconjunctival application.

In terms of ocular drug delivery, biodegradable implant systems have several advantages including the ability to provide constant drug concentration at the target site, no necessity for surgical removal, and minimum systemic side effects. Cyclosporin A (CsA) is a neutral, hydrophobic, cyclic peptide of amino acids that frequently used for dry eye disease treatment. The aim of this study was to develop a nanoparticle-loaded implant system for sustained-release CsA delivery following subconjunctival implantation.

Development and evaluation of paclitaxel nanoparticles using a quality-by-design approach.

The aims of this study were to develop and characterize paclitaxel nanoparticles, to identify and control critical sources of variability in the process, and to understand the impact of formulation and process parameters on the critical quality attributes (CQAs) using a quality-by-design (QbD) approach. For this, a risk assessment study was performed with various formulation and process parameters to determine their impact on CQAs of nanoparticles, which were determined to be average particle size, zeta potential, and encapsulation efficiency. Potential risk factors were identified using an Ishikawa diagram and screened by Plackett-Burman design and finally nanoparticles were optimized using Box-Behnken design.

5-Fluorouracil-loaded PLA/PLGA PEG-PPG-PEG polymeric nanoparticles: formulation, in vitro characterization and cell culture studies.

In this study, 5-FU, a potent anticancer drug, is planned to be delivered via a new and promising drug delivery system, nanoparticles formed with hydrophobic core polymer and triblock copolymers; Poly(DL-lactic acid), Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymer (PLA/PEG-PPG-PEG) and Poly(D,L-lactide-co-glycolide)/Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymer (PLGA/PEG-PPG-PEG) nanoparticles. Particle size range of nanoparticles was found to be between 145 and 198 nm, which would promote the passive targeting of the nanoparticles to tumor cells based on the enhanced permeability and retention (EPR) effect. SEM images revealed all nanoparticles formulations to be spherical and without pores.

In vitro studies on 5-florouracil-loaded DTPA-PE containing nanosized pegylated liposomes for diagnosis and treatment of tumor.

Theranostic liposomes carry both the therapeutic active ingredients and the contrast agent into one delivery system. Codelivery of imaging contrast agent and chemotherapeutic drugs can provide real-time validation of the targeting strategy, resulting in an another step forward for individual-based therapy. The aim of this study was the incorporation of different drugs used in the diagnosis and treatment of tumors into one delivery system to develop nanosized, polyethylene glycol (PEG)-coated, different charged theranostic liposomes.

Long-circulating PEG-PE micelles co-loaded with paclitaxel and elacridar (GG918) overcome multidrug resistance.

Overexpression of drug efflux pump P-gp is one of the major reasons to cause multidrug resistance (MDR). To overcome P-gp mediated MDR, modulators, so called P-gp inhibitors, can be used to block efflux pump activity. Elacridar is one of the most potent P-gp inhibitors, which can cause irreversible and total P-gp blockage.