Nanoparticles for Small Molecule Drug Delivery is a group in Biological Sciences on Mendeley.
Adair, J.H. et al., 2010. Nanoparticulate alternatives for drug delivery. ACS nano, 4(9), pp.4967-70. Available at: http://dx.doi.org/10.1021/nn102324e [Accessed April 8, 2012].
Abstract: The ability to apply nanomaterials as targeted delivery agents for drugs and other therapeutics holds promise for a wide variety of diseases, including many types of cancer. A nanodelivery vehicle must demonstrate in vivo efficacy, diminished or no toxicity, stability, improved pharmacokinetics, and controlled-release kinetics. In this issue, Lee et al. construct polymer nanobins that fulfill these requirements and demonstrate effective delivery of doxorubicin in vivo to breast cancer cells. This Perspective explores the outlook for these nanobins as well as other technologies in this field and the challenges that lie ahead.
Chen, Y., Dalwadi, G. & Benson, H.A.E., 2004. Drug delivery across the blood-brain barrier. Current drug delivery, 1(4), pp.361-76. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16305398 [Accessed April 8, 2012].
Abstract: The brain is protected and isolated from the general circulation by a highly efficient blood-brain barrier. This is characterised by relatively impermeable endothelial cells with tight junctions, enzymatic activity and active efflux transport systems. Consequently the blood-brain barrier is designed to permit selective transport of molecules that are essential for brain function. This creates a considerable challenge for the treatment of central nervous system diseases requiring therapeutic levels of drug to enter the brain. Some small lipophilic drugs diffuse across the blood-brain barrier- sufficiently well to be efficacious. However, many potentially useful drugs are excluded. This review provides an insight into the current research into technologies to target small molecules, peptides and proteins to the brain. A brief review of the nature of the blood-brain barrier and its transport mechanisms is provided. Strategies to target and improve transport across the blood-brain barrier include the prodrug-lipidisation approach, sequential metabolism chemical delivery systems, drug-vectors, liposomes and nanoparticles. Included is the discussion of techniques to minimise clearance from the circulation by the reticuloendothelial system in order to extend circulation residence time and optimise the opportunity for interaction between the drug delivery system and the blood-brain barrier.
Chen, Z.G., 2010. Small-molecule delivery by nanoparticles for anticancer therapy. Trends in molecular medicine, 16(12), pp.594-602. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20846905 [Accessed March 15, 2012].
Abstract: Using nanoparticles for the delivery of small molecules in anticancer therapy is a rapidly growing area of research. The advantages of using nanoparticles for drug delivery include enhanced water solubility, tumor-specific accumulation and improved antitumor efficacy, while reducing nonspecific toxicity. Current research in this field focuses on understanding precisely how small molecules are released from nanoparticles and delivered to the targeted tumor tissues or cells, and how the unique biodistribution of the drug-carrying nanoparticles limits toxicity in major organs. Here, we discuss existing nanoparticles for the delivery of small-molecule anticancer agents and recent advances in this field.
Danhier, F. et al., 2012. PLGA-based nanoparticles: An overview of biomedical applications. Journal of controlled release : official journal of the Controlled Release Society. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22353619 [Accessed March 21, 2012].
Abstract: Poly(lactic-co-glycolic acid) (PLGA) is one of the most successfully developed biodegradable polymers. Among the different polymers developed to formulate polymeric nanoparticles, PLGA has attracted considerable attention due to its attractive properties: (i) biodegradability and biocompatibility, (ii) FDA and European Medicine Agency approval in drug delivery systems for parenteral administration, (iii) well described formulations and methods of production adapted to various types of drugs e.g. hydrophilic or hydrophobic small molecules or macromolecules, (iv) protection of drug from degradation, (v) possibility of sustained release, (vi) possibility to modify surface properties to provide stealthness and/or better interaction with biological materials and (vii) possibility to target nanoparticles to specific organs or cells. This review presents why PLGA has been chosen to design nanoparticles as drug delivery systems in various biomedical applications such as vaccination, cancer, inflammation and other diseases. This review focuses on the understanding of specific characteristics exploited by PLGA-based nanoparticles to target a specific organ or tissue or specific cells.
Faraji, A.H. & Wipf, P., 2009. Nanoparticles in cellular drug delivery. Bioorganic & medicinal chemistry, 17(8), pp.2950-62. Available at: http://dx.doi.org/10.1016/j.bmc.2009.02.043 [Accessed March 14, 2012].
Abstract: This review highlights the properties of nanoparticles used in targeted drug delivery, including delivery to cells as well as organelle targets, some of the known pharmacokinetic properties of nanoparticles, and their typical modifications to allow for therapeutic delivery. Nanoparticles exploit biological pathways to achieve payload delivery to cellular and intracellular targets, including transport past the blood-brain barrier. As illustrative examples of their utility, the evaluation of targeted nanoparticles in the treatment of cancers and diseases of the central nervous system, such as glioblastoma multiforme, neurovascular disorders, and neurodegenerative diseases, is discussed.
Farokhzad, O.C. & Langer, R., 2009. Impact of nanotechnology on drug delivery. ACS nano, 3(1), pp.16-20. Available at: http://dx.doi.org/10.1021/nn900002m [Accessed March 19, 2012].
Abstract: Nanotechnology is the engineering and manufacturing of materials at the atomic and molecular scale. In its strictest definition from the National Nanotechnology Initiative, nanotechnology refers to structures roughly in the 1-100 nm size regime in at least one dimension. Despite this size restriction, nanotechnology commonly refers to structures that are up to several hundred nanometers in size and that are developed by top-down or bottom-up engineering of individual components. Herein, we focus on the application of nanotechnology to drug delivery and highlight several areas of opportunity where current and emerging nanotechnologies could enable entirely novel classes of therapeutics.
Gaumet, M. et al., 2008. Nanoparticles for drug delivery: the need for precision in reporting particle size parameters. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V, 69(1), pp.1-9. Available at: http://dx.doi.org/10.1016/j.ejpb.2007.08.001 [Accessed March 12, 2012].
Abstract: Polymeric drug-loaded nanoparticles have been extensively studied in the field of drug delivery. Biodistribution depends on the physicochemical properties of particles, especially size. The global message from the literature is that small particles have an enhanced ability to reach their target. The present review highlights the difficulties in validating the data from biodistribution studies without accurate particle size determination.
Hu, Y. et al., 2007. Cytosolic delivery of membrane-impermeable molecules in dendritic cells using pH-responsive core-shell nanoparticles. Nano letters, 7(10), pp.3056-64. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17887715 [Accessed April 8, 2012].
Abstract: Polycations that absorb protons in response to the acidification of endosomes can theoretically disrupt these vesicles via the “proton sponge” effect. To exploit this mechanism, we created nanoparticles with a segregated core-shell structure for efficient, noncytotoxic intracellular drug delivery. Cross-linked polymer nanoparticles were synthesized with a pH-responsive core and hydrophilic charged shell designed to disrupt endosomes and mediate drug/cell binding, respectively. By sequestering the relatively hydrophobic pH-responsive core component within a more hydrophilic pH-insensitive shell, nontoxic delivery of small molecules and proteins to the cytosol was achieved in dendritic cells, a key cell type of interest in the context of vaccines and immunotherapy.
Irvine, D.J., 2011. Drug delivery: One nanoparticle, one kill. Nature materials, 10(5), pp.342-3. Available at: http://dx.doi.org/10.1038/nmat3014 [Accessed March 2, 2012].
Jain, K.K., 2006. Nanoparticles as targeting ligands. Trends in biotechnology, 24(4), pp.143-5. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16488033 [Accessed April 8, 2012].
Abstract: A recently published technique enables the attachment of small molecules to nanoparticles for improved targeting of nanomaterials. This new methodology has been compared with some of the other nanoparticle-based techniques for target discovery and found to be more versatile and specific. This approach has potential for high-throughput drug discovery, improved drug delivery and linking of diagnostics to therapeutics for the development of personalized medicines.
Janib, S.M., Moses, A.S. & MacKay, J.A., 2010. Imaging and drug delivery using theranostic nanoparticles. Advanced drug delivery reviews, 62(11), pp.1052-63. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20709124 [Accessed March 10, 2012].
Abstract: Nanoparticle technologies are significantly impacting the development of both therapeutic and diagnostic agents. At the intersection between treatment and diagnosis, interest has grown in combining both paradigms into clinically effective formulations. This concept, recently coined as theranostics, is highly relevant to agents that target molecular biomarkers of disease and is expected to contribute to personalized medicine. Here we review state-of-the-art nanoparticles from a therapeutic and a diagnostic perspective and discuss challenges in bringing these fields together. Major classes of nanoparticles include, drug conjugates and complexes, dendrimers, vesicles, micelles, core-shell particles, microbubbles, and carbon nanotubes. Most of these formulations have been described as carriers of either drugs or contrast agents. To observe these formulations and their interactions with disease, a variety of contrast agents have been used, including optically active small molecules, metals and metal oxides, ultrasonic contrast agents, and radionuclides. The opportunity to rapidly assess and adjust treatment to the needs of the individual offers potential advantages that will spur the development of theranostic agents.
Nie, S. et al., 2007. Nanotechnology applications in cancer. Annual review of biomedical engineering, 9, pp.257-88. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17439359 [Accessed March 3, 2012].
Abstract: Cancer nanotechnology is an interdisciplinary area of research in science, engineering, and medicine with broad applications for molecular imaging, molecular diagnosis, and targeted therapy. The basic rationale is that nanometer-sized particles, such as semiconductor quantum dots and iron oxide nanocrystals, have optical, magnetic, or structural properties that are not available from molecules or bulk solids. When linked with tumor targeting ligands such as monoclonal antibodies, peptides, or small molecules, these nanoparticles can be used to target tumor antigens (biomarkers) as well as tumor vasculatures with high affinity and specificity. In the mesoscopic size range of 5-100 nm diameter, nanoparticles also have large surface areas and functional groups for conjugating to multiple diagnostic (e.g., optical, radioisotopic, or magnetic) and therapeutic (e.g., anticancer) agents. Recent advances have led to bioaffinity nanoparticle probes for molecular and cellular imaging, targeted nanoparticle drugs for cancer therapy, and integrated nanodevices for early cancer detection and screening. These developments raise exciting opportunities for personalized oncology in which genetic and protein biomarkers are used to diagnose and treat cancer based on the molecular profiles of individual patients.
Paulo, C.S.O., Pires das Neves, R. & Ferreira, L.S., 2011. Nanoparticles for intracellular-targeted drug delivery. Nanotechnology, 22(49), p.494002. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22101232 [Accessed March 11, 2012].
Abstract: Nanoparticles (NPs) are very promising for the intracellular delivery of anticancer and immunomodulatory drugs, stem cell differentiation biomolecules and cell activity modulators. Although initial studies in the area of intracellular drug delivery have been performed in the delivery of DNA, there is an increasing interest in the use of other molecules to modulate cell activity. Herein, we review the latest advances in the intracellular-targeted delivery of short interference RNA, proteins and small molecules using NPs. In most cases, the drugs act at different cellular organelles and therefore the drug-containing NPs should be directed to precise locations within the cell. This will lead to the desired magnitude and duration of the drug effects. The spatial control in the intracellular delivery might open new avenues to modulate cell activity while avoiding side-effects.
Quan, Q. et al., 2011. HSA coated iron oxide nanoparticles as drug delivery vehicles for cancer therapy. Molecular pharmaceutics, 8(5), pp.1669-76. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3185217&tool=pmcentrez&rendertype=abstract [Accessed April 1, 2012].
Abstract: An ongoing effort in the field of nanomedicine is to develop nanoplatforms with both imaging and therapeutic functions, the “nanotheranostics”. We have previously developed a human serum albumin (HSA) coated iron oxide nanoparticle (HINP) formula and used multiple imaging modalities to validate its tumor targeting attributes. In the current study, we sought to impart doxorubicin (Dox) onto the HINPs and to assess the potential of the conjugates as theranostic agents. In a typical preparation, we found that about 0.5 mg of Dox and 1 mg of iron oxide nanoparticles (IONPs, Fe content) could be loaded into 10 mg of HSA matrices. The resulting D-HINPs (Dox loaded HINPs) have a hydrodynamic size of 50 nm and are able to release Dox in a sustained fashion. More impressively, the HINPs can assist the translocation of Dox across the cell membrane and even its accumulation in the nucleus. In vivo, D-HINPs retained a tumor targeting capability of HINPs, as manifested by both in vivo MRI and ex vivo immunostaining results. In a follow-up therapeutic study on a 4T1 murine breast cancer xenograft model, D-HINPs showed a striking tumor suppression effect that was comparable to that of Doxil and greatly outperformed free Dox. Such a strategy can be readily extended to load other types of small molecules, making HINP a promising theranostic nanoplatform.
Silva, G.A., 2008. Nanotechnology approaches to crossing the blood-brain barrier and drug delivery to the CNS. BMC neuroscience, 9 Suppl 3, p.S4. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2604882&tool=pmcentrez&rendertype=abstract [Accessed April 6, 2012].
Abstract: Nanotechnologies are materials and devices that have a functional organization in at least one dimension on the nanometer (one billionth of a meter) scale, ranging from a few to about 100 nanometers. Nanoengineered materials and devices aimed at biologic applications and medicine in general, and neuroscience in particular, are designed fundamentally to interface and interact with cells and their tissues at the molecular level. One particularly important area of nanotechnology application to the central nervous system (CNS) is the development of technologies and approaches for delivering drugs and other small molecules such as genes, oligonucleotides, and contrast agents across the blood brain barrier (BBB). The BBB protects and isolates CNS structures (i.e. the brain and spinal cord) from the rest of the body, and creates a unique biochemical and immunological environment. Clinically, there are a number of scenarios where drugs or other small molecules need to gain access to the CNS following systemic administration, which necessitates being able to cross the BBB. Nanotechnologies can potentially be designed to carry out multiple specific functions at once or in a predefined sequence, an important requirement for the clinically successful delivery and use of drugs and other molecules to the CNS, and as such have a unique advantage over other complimentary technologies and methods. This brief review introduces emerging work in this area and summarizes a number of example applications to CNS cancers, gene therapy, and analgesia.
Singh, R. & Lillard, J.W., 2009. Nanoparticle-based targeted drug delivery. Experimental and molecular pathology, 86(3), pp.215-23. Available at: http://dx.doi.org/10.1016/j.yexmp.2008.12.004 [Accessed March 15, 2012].
Abstract: Nanotechnology could be defined as the technology that has allowed for the control, manipulation, study, and manufacture of structures and devices in the “nanometer” size range. These nano-sized objects, e.g., “nanoparticles”, take on novel properties and functions that differ markedly from those seen from items made of identical materials. The small size, customized surface, improved solubility, and multi-functionality of nanoparticles will continue to open many doors and create new biomedical applications. Indeed, the novel properties of nanoparticles offer the ability to interact with complex cellular functions in new ways. This rapidly growing field requires cross-disciplinary research and provides opportunities to design and develop multifunctional devices that can target, diagnose, and treat devastating diseases such as cancer. This article presents an overview of nanotechnology for the biologist and discusses the attributes of our novel XPclad((c)) nanoparticle formulation that has shown efficacy in treating solid tumors, single dose vaccination, and oral delivery of therapeutic proteins.
Sun, D. et al., 2010. A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Molecular therapy : the journal of the American Society of Gene Therapy, 18(9), pp.1606-14. Available at: http://dx.doi.org/10.1038/mt.2010.105 [Accessed March 29, 2012].
Abstract: Monocyte-derived myeloid cells play vital roles in inflammation-related autoimmune/inflammatory diseases and cancers. Here, we report that exosomes can deliver anti-inflammatory agents, such as curcumin, to activated myeloid cells in vivo. This technology provides a means for anti-inflammatory drugs, such as curcumin, to target the inflammatory cells as well as to overcome unwanted off-target effects that limit their utility. Using exosomes as a delivery vehicle, we provide evidence that curcumin delivered by exosomes is more stable and more highly concentrated in the blood. We show that the target specificity is determined by exosomes, and the improvement of curcumin activity is achieved by directing curcumin to inflammatory cells associated with therapeutic, but not toxic, effects. Furthermore, we validate the therapeutic relevance of this technique in a lipopolysaccharide (LPS)-induced septic shock mouse model. We further show that exosomes, but not lipid alone, are required for the enhanced anti-inflammatory activity of curcumin. The specificity of using exosomes as a drug carrier creates opportunities for treatments of many inflammation-related diseases without significant side effects due to innocent bystander or off-target effects.
Wang, M.D. et al., 2007. Nanotechnology for targeted cancer therapy. Expert review of anticancer therapy, 7(6), pp.833-7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17555393 [Accessed April 8, 2012].
Abstract: Cancer nanotechnology is currently under intense development for applications in cancer imaging, molecular diagnosis and targeted therapy. The basic rationale is that nanometer-sized particles, such as biodegradable micelles, semiconductor quantum dots and iron oxide nanocrystals, have functional or structural properties that are not available from either molecular or macroscopic agents. When linked with biotargeting ligands, such as monoclonal antibodies, peptides or small molecules, these nanoparticles are used to target malignant tumors with high affinity and specificity. In the “mesoscopic” size range of 5-100 nm in diameter, nanoparticles also have large surface areas and functional groups for conjugating to multiple diagnostic (e.g., optical, radioisotopic or magnetic) and therapeutic (e.g., anticancer) agents. Recent advances have led to multifunctional nanoparticle probes for molecular and cellular imaging, nanoparticle drugs for targeted therapy, and integrated nanodevices for early cancer detection and screening. These developments have opened exciting opportunities for personalized oncology in which cancer detection, diagnosis and therapy are tailored to each individual’s molecular profile, and also for predictive oncology, in which genetic/molecular information is used to predict tumor development, progression and clinical outcome.
Yoo, J. et al., 2012. Synthesis of the first poly(diaminosulfide)s and an investigation of their applications as drug delivery vehicles. Macromolecules, 45(2), pp.688-697. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3280910&tool=pmcentrez&rendertype=abstract [Accessed April 8, 2012].
Abstract: This paper reports the first examples of poly(diaminosulfide)s that were synthesized by the reaction of a sulfur transfer reagent and several secondary diamines. The diaminosulfide group has the general structure of R(2)N-S-NR(2) and, although it has been used in the synthesis of small molecules, it has never been utilized in the synthesis of macromolecules until this report. A series of poly(diaminosulfide)s were synthesized at elevated temperatures, and the molecular weights of the polymers were as high as 12,400 g mol(-1) with conversions for the polymerization reaction up to 99%. The rate constants for the transamination reactions that lead to the polymers were measured in several solvents to provide an understanding the reaction conditions necessary to polymerize the monomers. The degradation of diaminosulfides were studied in D(2)O, C(6)D(6), CD(3)OD, CDCl(3), and DMSO-d(6)/D(2)O to demonstrate that they were very stable in organic solvents but degraded within hours under aqueous conditions. These results clearly demonstrated that diaminosulfides are very stable in organic solvents under ambient conditions. Poly(diaminosulfide)s have sufficient stabilities to be useful for many applications. The ability of these polymers to function as drug delivery vehicles were studied by the fabrication of nanoparticles of a water-insoluble poly(diaminosulfide) with a dye. The microparticles were readily absorbed into human embryonic 293 cells and possessed no measureable toxicity towards these same cells.
