Chitosan magnetic nanoparticles for drug delivery systems

The potential of magnetic nanoparticles (MNPs) in drug delivery systems (DDSs) is mainly related to its magnetic core and surface coating. These coatings can eliminate or minimize their aggregation under physiological conditions. Also, they can provide functional groups for bioconjugation to anticancer drugs and/or targeted ligands. Chitosan, as a derivative of chitin, is an attractive natural biopolymer from renewable resources with the presence of reactive amino and hydroxyl functional groups in its structure. Chitosan nanoparticles (NPs), due to their huge surface to volume ratio as compared to the chitosan in its bulk form, have outstanding physico-chemical, antimicrobial and biological properties. These unique properties make chitosan NPs a promising biopolymer for the application of DDSs. In this review, the current state and challenges for the application magnetic chitosan NPs in drug delivery systems were investigated. The present review also revisits the limitations and commercial impediments to provide insight for future works.     

Chitosan and lactic acid-grafted chitosan nanoparticles as carriers for prolonged drug delivery

Nanoparticles of approximately 10nm in diameter made with chitosan or lactic acid-grafted chitosan were developed for high drug loading and prolonged drug release. A drug encapsulation efficiency of 92% and a release rate of 28% from chitosan nanoparticles over a 4-week period were demonstrated with bovine serum protein. To further increase drug encapsulation, prolong drug release, and increase chitosan solubility in solution of neutral pH, chitosan was modified with lactic acid by grafting D,L-lactic acid onto amino groups in chitosan without using a catalyst. The lactic acid-grafted chitosan nanoparticles demonstrated a drug encapsulation efficiency of 96% and a protein release rate of 15% over 4 weeks. With increased protein concentration, the drug encapsulation efficiency decreased and drug release rate increased. Unlike chitosan, which is generally soluble only in acid solution, the chitosan modified with lactic acid can be prepared from solutions of neutral pH, offering an additional advantage of allowing proteins or drugs to be uniformly incorporated in the matrix structure with minimal or no denaturization.     

Peptide-based hydrogel nanoparticles as effective drug delivery agents

Peptide-based hydrogel nanoparticles represent a promising alternative to current drug delivery approaches. We have previously demonstrated that the Fmoc-FF aromatic dipeptide building block can self-assemble in aqueous solutions to form nano-scaled ordered hydrogels of remarkable mechanical rigidity. Here, we present a scalable process for the assembly of this peptide into hydrogel nanoparticles (HNPs) aimed to be utilized as potential drug delivery carriers. Fmoc-FF based HNPs were formulated via modified inverse-emulsion method using vitamin E-TPGS as an emulsion stabilizer and high speed homogenization. The formed HNPs exhibited two distinguishable populations with an average size of 21.5 ± 1.3 and 225.9 ± 0.8 nm. Gold nanoparticles were encapsulated within the hydrogel nanoparticles as contrast agents to monitor the formation of the assemblies and their ultrastructural properties. Next, we demonstrated a robust experimental procedure developed and optimized for the formulation, purification, storage and handling procedures of HNPs. Encapsulation of doxorubicin (Dox) and 5-flourouracil (5-Fu) within the HNPs matrix showed release kinetics of the drugs depending on their chemical structure, molecular weight and hydrophobicity. The results clearly indicate that Fmoc-FF based hydrogel nanoparticles have the potential to be used as encapsulation and delivery system of various drugs and bioactive molecules.     

Magnetic nanoparticles for gene and drug delivery

Investigations of magnetic micro- and nanoparticles for targeted drug delivery began over 30 years ago. Since that time, major progress has been made in particle design and synthesis techniques, however, very few clinical trials have taken place. Here we review advances in magnetic nanoparticle design, in vitro and animal experiments with magnetic nanoparticle-based drug and gene delivery, and clinical trials of drug targeting.     

Chitosan nanoparticles for oral drug and gene delivery

Chitosan is a widely available, mucoadhesive polymer that is able to increase cellular permeability and improve the bioavailability of orally administered protein drugs. It can also be readily formed into nanoparticles able to entrap drugs or condense plasmid DNA. Studies on the formulation and oral delivery of such chitosan nanoparticles have demonstrated their efficacy in enhancing drug uptake and promoting gene expression. This review summarizes some of these findings and highlights the potential of chitosan as a component of oral delivery systems.     

AS1411 aptamer tagged PLGA-lecithin-PEG nanoparticles for tumor cell targeting and drug delivery

Liposomes and polymers are widely used drug carriers for controlled release since they offer many advantages like increased treatment effectiveness, reduced toxicity and are of biodegradable nature. In this work, anticancer drug‐loaded PLGA‐lecithin‐PEG nanoparticles (NPs) were synthesized and were functionalized with AS1411 anti‐nucleolin aptamers for site‐specific targeting against tumor cells which over expresses nucleolin receptors. The particles were characterized by transmission electron microscope (TEM) and X‐ray photoelectron spectroscopy (XPS). The drug‐loading efficiency, encapsulation efficiency and in vitro drug release studies were conducted using UV spectroscopy. Cytotoxicity studies were carried out in two different cancer cell lines, MCF‐7 and GI‐1 cells and two different normal cells, L929 cells and HMEC cells. Confocal microscopy and flowcytometry confirmed the cellular uptake of particles and targeted drug delivery. The morphology analysis of the NPs proved that the particles were smooth and spherical in shape with a size ranging from 60 to 110 nm. Drug‐loading studies indicated that under the same drug loading, the aptamer‐targeted NPs show enhanced cancer killing effect compared to the corresponding non‐targeted NPs. In addition, the PLGA‐lecithin‐PEG NPs exhibited high encapsulation efficiency and superior sustained drug release than the drug loaded in plain PLGA NPs. The results confirmed that AS1411 aptamer‐PLGA‐lecithin‐PEG NPs are potential carrier candidates for differential targeted drug delivery. Biotechnol. Bioeng. 2012; 109: 2920–2931. © 2012 Wiley Periodicals, Inc.     

Nanocarriers as pulmonary drug delivery systems to treat and to diagnose respiratory and non respiratory diseases

The purpose of this review is to discuss the impact of nanocarriers administered by pulmonary route to treat and to diagnose respiratory and non respiratory diseases. Indeed, during the past 10 years, the removal of chlorofluorocarbon propellants from industrial and household products intended for the pulmonary route has lead to the developments of new alternative products. Amongst these ones, on one hand, a lot of attention has been focused to improve the bioavailability of marketed drugs intended for respiratory diseases and to develop new concepts for pulmonary administration of drugs and, on the other hand, to use the pulmonary route to administer drugs for systemic diseases. This has led to some marketed products through the last decade. Although the introduction of nanotechnology permitted to step over numerous problems and to improve the bioavailability of drugs, there are, however, unresolved delivery problems to be still addressed. These scientific and industrial innovations and challenges are discussed along this review together with an analysis of the current situation concerning the industrial developments.     

Chemotherapy drug delivery from calcium phosphate nanoparticles

Calcium phosphate nanoparticles (nanoCaP) conjugated with cis-diamminedichloroplatinum (CDDP, cisplatin) were prepared through the electrostatic binding of an aquated species of cisplatin to the nanoCaP in a chloride-free solution. The agglomeration of the nanoCaP that typically occurs during synthesis of CaP was controlled through the addition of DARVAN 811 immediately after precipitation and before drug conjugation. In vitro drug release studies were completed and showed a sustained release of CDDP from the nanoconjugates over time. The cytotoxicity of the nanoCaP/CDDP was compared to that of the free drug in an in vitro cell proliferation assay using the CDDP resistant A2780cis human ovarian cancer cell line. The CDDP released from the nanoconjugates was equally effective as the free drug against the A2780cis cell line. Direct addition cytotoxicity studies revealed that the sterically-stabilized, negatively-charged drug nanoconjugates are unable to overcome drug resistance and had an increased IC50 value as compared to the free drug.     

Drug delivery and nanoparticles:applications and hazards

The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed.     

Tumor extracellular acidity-activated nanoparticles as drug delivery systems for enhanced cancer therapy

pH-responsive nanoparticles (NPs) are currently under intense development as drug delivery systems for cancer therapy. Among various pH-responsiveness, NPs that are designed to target slightly acidic extracellular pH environment (pH_e) of solid tumors provide a new paradigm of tumor targeted drug delivery. Compared to conventional specific surface targeting approaches, the pH_e-targeting strategy is considered to be more general due to the common occurrence of acidic microenvironment in solid tumors. This review mainly focuses on the design and applications of pH_e-activated NPs, with special emphasis on pH_e-activated surface charge reversal NPs, for drug and siRNA delivery to tumors. The novel development of NPs described here offers great potential for achieving better therapeutic effects in cancer treatment.     

Design and evaluation of succinylated soy protein tablets as delayed drug delivery systems

The impact of succinylation on soy proteins as excipients for delayed delivery of drugs in the gastrointestinal tract was studied. Succinylation decreased protein solubility and protein charge density at pH 1.2 and increased solubility and zeta potential at pH above 4.5. Tablet erosion and swelling were decreased at pH 1.2 and increased at pH 7.5. FTIR analysis indicated polypeptide chain unfolding as a result of succinylation. Tablets of protein succinylated 50% or 100% released less than 10% of loaded riboflavin or rifampicin in 2 h at gastric pH in the presence of pepsin but released these compounds rapidly at intestinal pH. Succinylated soy protein tablets were thus gastroresistant, suggesting their use as excipients for controlled release of medicinal or nutraceutical agents.     

Magnetic nanoparticles for multi-imaging and drug delivery

Various bio-medical applications of magnetic nanoparticles have been explored during the past few decades. As tools that hold great potential for advancing biological sciences, magnetic nanoparticles have been used as platform materials for enhanced magnetic resonance imaging (MRI) agents, biological separation and magnetic drug delivery systems, and magnetic hyperthermia treatment. Furthermore, approaches that integrate various imaging and bioactive moieties have been used in the design of multi-modality systems, which possess synergistically enhanced properties such as better imaging resolution and sensitivity, molecular recognition capabilities, stimulus responsive drug delivery with on-demand control, and spatio-temporally controlled cell signal activation. Below, recent studies that focus on the design and synthesis of multi-mode magnetic nanoparticles will be briefly reviewed and their potential applications in the imaging and therapy areas will be also discussed.     

Microparticles and nanoparticles for drug delivery

Particulate drug delivery systems have become important in experimental pharmaceutics and clinical medicine. The distinction is often made between micro- and nanoparticles, being particles with dimensions best described in micrometers and nanometers respectively. That size difference entails real differences at many levels, from formulation to in vivo usage. Here I will discuss those differences and provide examples of applications, for local and systemic drug delivery. I will outline a number of challenges of interest in particulate drug delivery.     

Light-sensitive lipid-based nanoparticles for drug delivery: design principles and future considerations for biological applications

Abstract

Radiation-based therapies aided by nanoparticles have been developed for decades, and can be primarily categorized into two main platforms. First, delivery of payload of photo-reactive drugs (photosensitizers) using the conventional nanoparticles, and second, design and development of photo-triggerable nanoparticles (primarily liposomes) to attain light-assisted on-demand drug delivery. The main focus of this review is to provide an update of the history, current status and future applications of photo-triggerable lipid-based nanoparticles (light-sensitive liposomes). We will begin with a brief overview on the applications of liposomes for delivery of photosensitizers, including the choice of photosensitizers for photodynamic therapy, as well as the currently available light sources (lasers) used for these applications. The main segment of this review will encompass the details of strategies used to develop photo-triggerable liposomes for their drug delivery function. The principles underlying the assembly of photoreactive lipids into nanoparticles (liposomes) and photo-triggering mechanisms will be presented. We will also discuss factors that limit the applications of these liposomes for in vivo triggered drug delivery and emerging concepts that may lead to the biologically viable photo-activation strategies. We will conclude with our view point on the future perspectives of light-sensitive liposomes in the clinic.     

Interaction of nanoparticles and cell-penetrating peptides with skin for transdermal drug delivery

Abstract

Topical or transdermal drug delivery is challenging because the skin acts as a natural and protective barrier. Therefore, several methods have been examined to increase the permeation of therapeutic molecules into and through the skin. One approach is to use the nanoparticulate delivery system. Starting with liposomes and other vesicular systems, several other types of nanosized drug carriers have been developed such as solid lipid nanoparticles, nanostructured lipid carriers, polymer-based nanoparticles and magnetic nanoparticles for dermatological applications. This review article discusses how different particulate systems can interact and penetrate into the skin barrier. In this review, the effectiveness of nanoparticles, as well as possible mode of actions of nanoparticles, is presented. In addition to nanoparticles, cell-penetrating peptide (CPP)-mediated drug delivery into the skin and the possible mechanism of CPP-derived delivery into the skin is discussed. Lastly, the effectiveness and possible mechanism of CPP-modified nanocarriers into the skin are addressed.     

Photocrosslinkable biodegradable responsive hydrogels as drug delivery systems

Recently, controlled release from biocompatible materials has received much attention for biomedical applications. Due to their biocompatibility and biodegradability, glucopyranosides such as dextran appear as promising polymeric materials if one is able to regulate their rheological properties and the encapsulation/release efficiency. In this work graft polymer hydrogels from dextran and N-isopropylacrylamide (NIPAAm) were prepared and characterized.Dextran molecules were modified with 2-isocyanatoethylmethacrylate (IEMA) in order to obtain a polymer with carbon double bonds. Urethane linkages resulted from the reaction between hydroxyl groups (OH) of the dextran and isocyanate groups (NCO) of the IEMA. The obtained polymer was then crosslinked by UV irradiation in the presence of the photoinitiating agent Irgacure 2959 by CIBA^®. The drug Ondansetron^® was entrapped in the final system and its release profile was determined at 25 and 37 °C.The characterization of the materials was accomplished by: ATR-FTIR (Attenuated Total Reflectance-Fourier Transform Infrared) spectroscopy, elemental analysis, lower critical solution temperature (LCST) determination, swelling behaviour evaluation, determination of surface energy by contact angle measurement and drug delivery profile studies.     

Curdlan gels as protein drug delivery vehicles

The use of curdlan, a natural -1,3-glucan, in protein drug delivery vehicles was studied by carrying out in vitro release studies with curdlan gels containing bovine serum albumin (BSA) as a model protein. Addition of urea (8 M) decreased the gel formation temperature to 37°C. Curdlan was hydroxyethylated in order to form gels under mild conditions such as physiological temperature and pH. In gels formed in 8 M urea solution, urea was almost released after 2 h while BSA was completely released after 45–100 h. The total time for complete release of BSA increased with curdlan concentration within gels. The strength of hydroxyethylated curdlan gels (385.7 dyne cm^–2) was weaker than that of curdlan gels formed in 8 M urea solution (6277 dyne cm^–2).     

Drug and gene delivery using gold nanoparticles

Monolayer-functionalized gold nanoparticles provide attractive vehicles for pharmaceutical delivery applications as a result of their size and the unique properties and release mechanisms imparted by their monolayer. This review provides examples of recent advances in the field of drug and gene delivery using gold nanoparticles.     

Reactive oxygen species responsive nanoplatforms as smart drug delivery systems for gastrointestinal tract targeting

The pharmacological therapy for gastrointestinal (GI) diseases, such as inflammatory bowel diseases, continues to present challenges in targeting efficacy. The need for maximal local drug exposure at the inflamed regions of the GI tract has led research to focus on a disease-targeted drug delivery approach. Smart nanomaterials responsive to the reactive oxygen species (ROS) concentrated in the inflamed areas, can be formulated into nanoplatforms to selectively release the active compounds, avoiding unspecific drug delivery to healthy tissues and limiting systemic absorption. Recent developments of ROS-responsive nanoplatforms include combination with other materials to obtain multi-responsive systems and modifications/derivatization to increase the interactions with biological tissues, cell uptake and targeting. This review describes the applications of ROS-responsive nanosystems for on-demand drug delivery to the GI tract.