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.

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Drug delivery and nanoparticles:applications and hazards

Utilization of polymers as biomaterials has greatly impacted the advancement of modern medicine. Specifically, polymeric biomaterials that are biodegradable provide the significant advantage of being able to be broken down and removed after they have served their function. Applications are wide ranging with degradable polymers being used clinically as surgical sutures and implants. In order to fit functional demand, materials with desired physical, chemical, biological, biomechanical and degradation properties must be selected. Fortunately, a wide range of natural and synthetic degradable polymers has been investigated for biomedical applications with novel materials constantly being developed to meet new challenges. This review summarizes the most recent advances in the field over the past 4 years, specifically highlighting new and interesting discoveries in tissue engineering and drug delivery applications.

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Biomedical Applications of Biodegradable Polymers

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Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles.

In this Review, we aim to provide an updated summary of the research related to hollow micro- and nanostructures, covering both their synthesis and their applications. After a brief introduction to the definition and classification of the hollow micro-/nanostructures, we discuss various synthetic strategies that can be grouped into three major categories, including hard templating, soft templating, and self-templating synthesis. For both hard and soft templating strategies, we focus on how different types of templates are generated and then used for creating hollow structures. At the end of each section, the structural and morphological control over the product is discussed. For the self-templating strategy, we survey a number of unconventional synthetic methods, such as surface-protected etching, Ostwald ripening, the Kirkendall effect, and galvanic replacement. We then discuss the unique properties and niche applications of the hollow structures in diverse fields, including micro-/nanocontainers and rea...

Synthesis, Properties, and Applications of Hollow Micro-/Nanostructures

Design and functionalization strategies for multifunctional nanocarriers (e.g., nanoparticles, micelles, polymersomes) based on biodegradable/biocompatible polymers intended to be employed for active targeting and drug delivery are reviewed. This review will focus on the nature of the polymers involved in the preparation of targeted nanocarriers, the synthesis methods to achieve the desired macromolecular architecture, the selected coupling strategy, the choice of the homing molecules (vitamins, hormones, peptides, proteins, etc.), as well as the various strategies to display them at the surface of nanocarriers. The resulting morphologies and the main colloidal features will be given as well as an overview of the biological activities, with a special focus on the main in vivo achievements.

Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery

Cationic albumin-conjugated pegylated nanoparticles as novel drug carrier for brain delivery.

Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration.

Monodisperse Temperature‐Sensitive Microcontainers

The aim of this study was to encapsulate nimodipine (NM) within methoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) nanoparticles and to investigate its brain targeting efficiency following intranasal administration. NM-loaded nanoparticles, prepared through an emulsion/solvent evaporation technique, were characterized in terms of size, zeta potential, NM loading and in vitro release. The nanoparticles were administered intranasally to rats, and the concentrations of NM in blood, cerebrospinal fluid (CSF) and brain tissues were monitored. The contribution of the olfactory pathway to the uptake of NM in the brain was determined by calculating the brain/plasma concentration ratios and “brain drug direct transport percentage (DTP)” following intranasal administration of the nanoparticles and the solution formulation. The results showed that MPEG-PLA nanoparticles had a mean particle size of 76.5 ± 7.4 nm, a negative surface charge and a 5.2% NM loading. In vitro release was moderate under sink conditi...

The brain targeting efficiency following nasally applied MPEG-PLA nanoparticles in rats.

The amphiphilic copolymer of poly(methoxy-polyethyleneglycol polycaprolactone) (MePEG-PCL) was synthesized. Micelles loading hydroxycamptothecin (HCPT) as a model drug were prepared by solid-dispersion and dialysis–hydration method. The MePEG-PCL micelles were further characterized in terms of critical association concentrations (CAC), PEG surface density, fixed aqueous layer thickness, in vitro drug release and in vivo pharmacokinetics and biodistribution. The results showed that longer polycaprolactone (PCL) chain length would lead to the reduction of CAC value, stabilized HCPT, increasing drug-loading coefficient, sparser PEG surface density and slower drug release patterns. On the other hand, longer PEG chain length would give rise to less negative zeta potential and larger fixed aqueous layer thickness, as well as sparser PEG surface density and quicker drug release. MePEG-PCL micelles with PEG molecular weight of 2,000, 5,000, 10,000 could extend the AUC of HCPT in blood compartment by 9.13, 13.82, 21.25 times and increase the AUC of 125I-HCPT in the tumor of S180 mice by 7.94, 11.32, 26.08-fold, respectively. It was suggested that the PEG and PCL chain length may play a very important role in the micelle’s in vitro properties and in vivo behavior.

Stealth MePEG-PCL micelles: effects of polymer composition on micelle physicochemical characteristics, in vitro drug release, in vivo pharmacokinetics in rats and biodistribution in S 180 tumor bearing mice

Yan Zhang

Papers

Cationic albumin-conjugated pegylated nanoparticles as novel drug carrier for brain delivery.

Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration.

Monodisperse Temperature‐Sensitive Microcontainers

The brain targeting efficiency following nasally applied MPEG-PLA nanoparticles in rats.

Stealth MePEG-PCL micelles: effects of polymer composition on micelle physicochemical characteristics, in vitro drug release, in vivo pharmacokinetics in rats and biodistribution in S 180 tumor bearing mice