Nanoparticles (NP) are solid colloidal particles ranging in size from 1 to 1000 nm that are utilized as drug delivery agents. The use of NPs to deliver drugs to the brain across the blood-brain barrier (BBB) may provide a significant advantage to current strategies. The primary advantage of NP carrier technology is that NPs mask the blood-brain barrier limiting characteristics of the therapeutic drug molecule. Furthermore, this system may slow drug release in the brain, decreasing peripheral toxicity. This review evaluates previous strategies of brain drug delivery, discusses NP transport across the BBB, and describes primary methods of NP preparation and characterization. Further, influencing manufacturing factors (type of polymers and surfactants, NP size, and the drug molecule) are detailed in relation to movement of the drug delivery agent across the BBB. Currently, reports evaluating NPs for brain delivery have studied anesthetic and chemotherapeutic agents. These studies are reviewed for efficacy and mechanisms of transport. Physiological factors such as phagocytic activity of the reticuloendothelial system and protein opsonization may limit the amount of brain delivered drug and methods to avoid these issues are also discussed. NP technology appears to have significant promise in delivering therapeutic molecules across the BBB.

Nanoparticle Technology for Drug Delivery Across the Blood-Brain Barrier

Successful cancer management depends on accurate diagnostics along with specific treatment protocols. Current diagnostic techniques need to be improved to provide earlier detection capabilities, and traditional chemotherapy approaches to cancer treatment are limited by lack of specificity and systemic toxicity. This review highlights advances in nanotechnology that have allowed the development of multifunctional platforms for cancer detection, therapy, and monitoring. Nanomaterials can be used as MRI, optical imaging, and photoacoustic imaging contrast agents. When used as drug carriers, nanoformulations can increase tumor exposure to therapeutic agents and result in improved treatment effects by prolonging circulation times, protecting entrapped drugs from degradation, and enhancing tumor uptake through the enhanced permeability and retention effect as well as receptor-mediated endocytosis. Multiple therapeutic agents such as chemotherapy, antiangiogenic, or gene therapy agents can be simultaneously delivered by nanocarriers to tumor sites to enhance the effectiveness of therapy. Additionally, imaging and therapy agents can be co-delivered to provide seamless integration of diagnostics, therapy, and follow-up, and different therapeutic modalities such as chemotherapy and hyperthermia can be co-administered to take advantage of synergistic effects. Liposomes, metallic nanoparticles, polymeric nanoparticles, dendrimers, carbon nanotubes, and quantum dots are examples of nanoformulations that can be used as multifunctional platforms for cancer theranostics. Nanomedicine approaches in cancer have great potential for clinically translatable advances that can positively impact the overall diagnostic and therapeutic process and result in enhanced quality of life for cancer patients. However, a concerted scientific effort is still necessary to fully explore long-term risks, effects, and precautions for safe human use.

Theranostic applications of nanomaterials in cancer: drug delivery, image-guided therapy, and multifunctional platforms.

This article reviews the developmental stages and strategies used to assess the biomedical utility of biopolymer albumin from the 1970s to early 2002. The basic method and mechanism(s) of preparation of albumin microspheres and subsequent modifications made to overcome the drawbacks of earlier approaches and the need for further developments are discussed, as are the processing parameters and the level of various ingredients affecting the physicochemical properties of the albumin microspheres. Different equations proposed by various investigators to modulate in vitro release kinetics are reviewed. The microscopic structural and surface properties, the chemical modification of the biopolymer (e.g., cationization, tagging with amino acids and sugar moieties) for tissue specificity or to influence the release profile and biodegradation are discussed. An array of potential diagnostic applications and the use of albumin microspheres as a drug delivery system are reviewed. Drug Dev. Res. 58:219–247, 2003.© 2003 Wiley-Liss, Inc.

Biopolymer albumin for diagnosis and in drug delivery

Human serum albumin (HSA) nanospheres of about 100 nm diameter were prepared using a pH-coacervation method whereby acetone was added to an HSA solution (pH 9.0). The particles obtained were cross-linked by glutaraldehyde. Increasing the pH of the HSA solution resulted in a gradual rise in the particle size of the resultant nanospheres. A higher cross-linking efficiency was obtained with increased glutaraldehyde concentration and cross-linking time. No significant differences in surface properties, as determined by zeta potential measurements, were recorded between particles prepared from HSA solutions with different pH. The nanospheres were quite stable over 4 days in both phosphate buffer saline (PBS) solution (pH 7.4) and rat serum, but degraded rapidly over 6 hours when incubated in PBS solution containing trypsin.

Preparation of sub-100 nm human serum albumin nanospheres using a pH-coacervation method.

Albumin microspheres and microcapsules: Methodology of manufacturing techniques

Albumin microspheres for intra-arterial tumour targeting. I: Pharmaceutical aspects

Although in vitro studies may show a compound to have antitumour activity, often its nonideal pharmaceutical and pharmacokinetic properties combine to reduce its clinical effectiveness. Attempts to use carriers for the vectoring of such agents to tumour areas have caused (inter alia) liposomes,nanoparticles and microspheres to be studied. Kanke et a1 (1980) have shown that organ distribution of nonbiodegradable microspheres (3-12pm) after IV injection is dependent upon their size. This communication reports our initial findings on the preparation,characterisation and release properties of human serum albumin microspheres that have been prepared for intraarterial delivery of cytotoxic agents following tumour capillary blockade.

Preparation and characterisation of albumin microspheres for intraarterial tumour targetting of cytotoxic compounds

Non-ideal pharmaceutical, pharmacokinetic and therapeutic properties often combine to reduce the effectiveness of cytotoxic compounds. For the vectoring of such compounds to target areas, liposomes, nanoparticles and microspheres have been suggested. Since organ distribution of the latter is dependent upon their size and shape, it is reasonable to attempt second order (1) targeting of microspheres on this basis. This contribution gives our results on the preparation of biodegradable albumin microspheres, and the release of organic molecules from microspheres of differing character.

J. G. McVie

Papers

Albumin microspheres for intra-arterial tumour targeting. I: Pharmaceutical aspects

Preparation and characterisation of albumin microspheres for intraarterial tumour targetting of cytotoxic compounds

Albumin Microspheres for Intraarterial Drug Targeting