Special Issue "Drug Delivery Using Nanotechnology"

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A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (31 October 2012)

Special Issue Editor

Guest Editor
Prof. Dr. Dong Moon Shin

1 Winnship Cancer Institute, Emory University 1365-C Clifton Road, Room 3094, Atlanta, GA 30322, USA
2 Department of Hematology and Medical Oncology, Emory University School of Medicine, Emory University 1365-C Clifton Road, Room 3094, Atlanta, GA 30322, USA
Phone: 404-778-5990
Fax: (404) 778-5520
Interests: nanotherapeutics; drug delivery; nanoimaging; cancer

Keywords

  • nanoparticles
  • nanotechnology
  • nanotherapeutics
  • drug delivery
  • polymers
  • ligands
  • EPR effects
  • cancer

Published Papers (9 papers)

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Research

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Open AccessArticle Development of a Novel Lipophilic, Magnetic Nanoparticle for in Vivo Drug Delivery
Pharmaceutics 2013, 5(2), 246-260; doi:10.3390/pharmaceutics5020246
Received: 25 February 2013 / Revised: 2 April 2013 / Accepted: 12 April 2013 / Published: 23 April 2013
Cited by 3 | PDF Full-text (4609 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the present study was to evaluate the transfection potential of chitosan-coated, green-fluorescent magnetic nanoparticles (MNPs) (chi-MNPs) after encapsulation inside polyethylglycol (PEG)ylated liposomes that produced lipid-encapsulated chitosan-coated MNPs (lip-MNPs), and also to evaluate how these particles would distribute in vivo [...] Read more.
The aim of the present study was to evaluate the transfection potential of chitosan-coated, green-fluorescent magnetic nanoparticles (MNPs) (chi-MNPs) after encapsulation inside polyethylglycol (PEG)ylated liposomes that produced lipid-encapsulated chitosan-coated MNPs (lip-MNPs), and also to evaluate how these particles would distribute in vivo after systemic injection. The transfection potential of both chi-MNPs and lip-MNPs was evaluated in vitro in rat brain endothelial 4 (RBE4) cells with and without applying a magnetic field. Subsequently, the MNPs were evaluated in vivo in young rats. The in vitro investigations revealed that the application of a magnetic field resulted in an increased cellular uptake of the particles. The lip-MNPs were able to transfect the RBE4 cells with an incidence of approximately 20% of a commercial transfection agent. The in vivo distribution studies revealed that lip-MNPs had superior pharmacokinetic properties due to evasion of the RES, including hepatic Kuppfer cells and macrophages in the spleen. In conclusion, we were able to design a novel lipid-encapsulated MNP with the ability to carry genetic material, with favorable pharmacokinetic properties, and under the influence of a magnetic field with the capability to mediate transfection in vitro. Full article
(This article belongs to the Special Issue Drug Delivery Using Nanotechnology)
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Open AccessArticle Analytical Electron Microscopy for Characterization of Fluid or Semi-Solid Multiphase Systems Containing Nanoparticulate Material
Pharmaceutics 2013, 5(1), 115-126; doi:10.3390/pharmaceutics5010115
Received: 13 September 2012 / Revised: 28 January 2013 / Accepted: 30 January 2013 / Published: 5 February 2013
Cited by 3 | PDF Full-text (2452 KB) | HTML Full-text | XML Full-text
Abstract
The analysis of nanomaterials in pharmaceutical or cosmetic preparations is an important aspect both in formulation development and quality control of marketed products. Despite the increased popularity of nanoparticulate compounds especially in dermal preparations such as emulsions, methods and protocols of analysis [...] Read more.
The analysis of nanomaterials in pharmaceutical or cosmetic preparations is an important aspect both in formulation development and quality control of marketed products. Despite the increased popularity of nanoparticulate compounds especially in dermal preparations such as emulsions, methods and protocols of analysis for the characterization of such systems are scarce. This work combines an original sample preparation procedure along with different methods of analytical electron microscopy for the comprehensive analysis of fluid or semi-solid dermal preparations containing nanoparticulate material. Energy-filtered transmission electron microscopy, energy-dispersive X-ray spectroscopy, electron energy loss spectroscopy and high resolution imaging were performed on model emulsions and a marketed product to reveal different structural aspects of both the emulsion bulk phase and incorporated nanosized material. An innovative analytical approach for the determination of the physical stability of the emulsion under investigation is presented. Advantages and limitations of the employed analytical imaging techniques are highlighted. Full article
(This article belongs to the Special Issue Drug Delivery Using Nanotechnology)
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Open AccessArticle Correlating Physicochemical Properties of Boronic Acid-Chitosan Conjugates to Glucose Adsorption Sensitivity
Pharmaceutics 2013, 5(1), 69-80; doi:10.3390/pharmaceutics5010069
Received: 28 August 2012 / Revised: 10 December 2012 / Accepted: 18 December 2012 / Published: 27 December 2012
Cited by 2 | PDF Full-text (1110 KB) | HTML Full-text | XML Full-text
Abstract
Phenyl boronic acid (PBA), which is known to interact with glucose, was covalently bonded to chitosan by direct reductive N-alkylation of chitosan with 4-formylphenylboronic acid (4-FPBA). Evidence of PBA bonding on chitosan was assessed by FTIR, ToF-SIMS, SEM, DSC and glucose [...] Read more.
Phenyl boronic acid (PBA), which is known to interact with glucose, was covalently bonded to chitosan by direct reductive N-alkylation of chitosan with 4-formylphenylboronic acid (4-FPBA). Evidence of PBA bonding on chitosan was assessed by FTIR, ToF-SIMS, SEM, DSC and glucose adsorption sensitivity measurements. FTIR spectra showed strong signals at 1560 and 630 cm−1 indicating the formation of p-substituted benzene. Similarly, ToF-SIMS analyses on the conjugates registered fragments of boron ion (B) at 11.0 m/z whose intensity increased in proportion to 4-FPBA loading. The degree to which PBA was bonded to chitosan was related to the 4-FPBA load used in the reaction (termed F1 through to F6 with increasing 4-FPBA load). Glucose adsorption sensitivity to PBA-bonded chitosan was directly related to the amount of PBA functionality within the conjugates and the physical nature of the matrices (porous or crystalline). Topographic analysis by SEM revealed that PBA-chitosan conjugates F1, F2 and F3 have porous matrices and their sensitivity to glucose adsorption was directly proportional to the degree of PBA substitution onto chitosan. Conversely, conjugates F4, F5 and F6 appeared crystalline under SEM and glucose adsorption sensitivity decreased in proportion to amount of PBA bonded to chitosan. The crystalline nature of the conjugates was confirmed by DSC, where the exothermic event related to the melting of the bonded PBA moiety, occurred at 338 °C. Thus, decreased sensitivity to glucose adsorption by the conjugates can be ascribed to the crystallinity imparted by increased content of the bonded PBA moiety, providing an optimal loading of PBA in terms of maximizing response to glucose. Full article
(This article belongs to the Special Issue Drug Delivery Using Nanotechnology)
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Open AccessArticle Composition Influence on Pulmonary Delivery of Rifampicin Liposomes
Pharmaceutics 2012, 4(4), 590-606; doi:10.3390/pharmaceutics4040590
Received: 18 September 2012 / Revised: 1 November 2012 / Accepted: 16 November 2012 / Published: 27 November 2012
Cited by 8 | PDF Full-text (2277 KB) | HTML Full-text | XML Full-text
Abstract
The effects of lipid concentration and composition on the physicochemical properties, aerosol performance and in vitro toxicity activity of several rifampicin-loaded liposomes were investigated. To this purpose, six liposome formulations containing different amounts of soy phosphatidylcholine and hydrogenated soy phosphatidylcholine, with and [...] Read more.
The effects of lipid concentration and composition on the physicochemical properties, aerosol performance and in vitro toxicity activity of several rifampicin-loaded liposomes were investigated. To this purpose, six liposome formulations containing different amounts of soy phosphatidylcholine and hydrogenated soy phosphatidylcholine, with and without cholesterol and oleic acid, were prepared and fully characterized. Uni- or oligo-lamellar, small (~100 nm), negatively charged (~60 mV) vesicles were obtained. Lipid composition affected aerosol delivery features of liposomal rifampicin; in particular, the highest phospholipid concentration led to a better packing of the vesicular bilayers with a consequent higher nebulization stability. The retention of drug in nebulized vesicles (NER%) was higher for oleic acid containing vesicles (55% ± 1.4%) than for the other samples (~47%). A549 cells were used to evaluate intracellular drug uptake and in vitro toxicity activity of rifampicin-loaded liposomes in comparison with the free drug. Cell toxicity was more evident when oleic acid containing liposomes were used. Full article
(This article belongs to the Special Issue Drug Delivery Using Nanotechnology)
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Open AccessArticle Impact of Molecular Weight on Lymphatic Drainage of a Biopolymer-Based Imaging Agent
Pharmaceutics 2012, 4(2), 276-295; doi:10.3390/pharmaceutics4020276
Received: 7 March 2012 / Revised: 23 April 2012 / Accepted: 8 May 2012 / Published: 23 May 2012
Cited by 12 | PDF Full-text (722 KB) | HTML Full-text | XML Full-text
Abstract
New lymphatic imaging technologies are needed to better assess immune function and cancer progression and treatment. Lymphatic uptake depends mainly on particle size (10–100 nm) and charge. The size of carriers for imaging and drug delivery can be optimized to maximize lymphatic [...] Read more.
New lymphatic imaging technologies are needed to better assess immune function and cancer progression and treatment. Lymphatic uptake depends mainly on particle size (10–100 nm) and charge. The size of carriers for imaging and drug delivery can be optimized to maximize lymphatic uptake, localize chemotherapy to lymphatic metastases, and enable visualization of treatment deposition. Toward this end, female BALB/c mice were injected subcutaneously in the hind footpad or forearm with a series of six different molecular weight hyaluronan (HA) near-infrared dye (HA-IR820) conjugates (ca. 5–200 nm). Mice were imaged using whole body fluorescent imaging over two weeks. HA-IR820 fluorescence was clearly visualized in the draining lymphatic capillaries, and in the popliteal and iliac or axillary lymph nodes. The 74-kDa HA-IR820 had the largest lymph node area-under-the-curve. In contrast to prior reports, mice bearing limb tumors exhibited three-fold longer retention of 74-kDa HA-IR820 in the popliteal node compared to mice without tumors. HA conjugate kinetics and disposition can be specifically tailored by altering their molecular weight. The specific lymphatic uptake and increased nodal retention of HA conjugates indicate significant potential for development as a natural biopolymer for intralymphatic drug delivery and imaging. Full article
(This article belongs to the Special Issue Drug Delivery Using Nanotechnology)

Review

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Open AccessReview The Potential Role of Nanotechnology in Therapeutic Approaches for Triple Negative Breast Cancer
Pharmaceutics 2013, 5(2), 353-370; doi:10.3390/pharmaceutics5020353
Received: 22 February 2013 / Revised: 16 May 2013 / Accepted: 24 May 2013 / Published: 18 June 2013
Cited by 4 | PDF Full-text (381 KB) | HTML Full-text | XML Full-text
Abstract
Triple Negative Breast Cancer, TNBC, a highly aggressive and metastatic type of breast cancer, is characterized by loss of expression of the estrogen receptor (ER), progesterone receptor (PR), and a lack of overexpression of the human epidermal growth [...] Read more.
Triple Negative Breast Cancer, TNBC, a highly aggressive and metastatic type of breast cancer, is characterized by loss of expression of the estrogen receptor (ER), progesterone receptor (PR), and a lack of overexpression of the human epidermal growth factor receptor 2 (HER2). It is a heterogeneous group of tumors with diverse histology, molecular uniqueness and response to treatment. Unfortunately, TNBC patients do not benefit from current anti-HER2 or hormone positive targeted breast cancer treatments; consequently, these patients rely primarily on chemotherapy. However, the 5-year survival rate for woman with metastatic TNBC is less than 30%. As a result of ineffective treatments, TNBC tumors often progress to metastatic lesions in the brain and lung. Brain metastases of invasive breast cancer are associated with 1 and 2 year survival rate of 20% and <2% respectively. Because the only current systemic treatment for TNBC is chemotherapy, alternative targeted therapies are urgently needed to improve the prognosis for TNBC patients. This review is focused on opportunities for developing new approaches for filling the current void in an effective treatment for TNBC patients. Full article
(This article belongs to the Special Issue Drug Delivery Using Nanotechnology)
Open AccessReview Delivery of Cancer Therapeutics Using Nanotechnology
Pharmaceutics 2013, 5(2), 294-317; doi:10.3390/pharmaceutics5020294
Received: 24 December 2012 / Revised: 15 April 2013 / Accepted: 3 May 2013 / Published: 15 May 2013
Cited by 15 | PDF Full-text (1014 KB) | HTML Full-text | XML Full-text
Abstract
Nanoparticles have been investigated as drug carriers, because they provide a great opportunity due to their advantageous features: (i) various formulations using organic/inorganic materials, (ii) easy modification of targeting molecules, drugs or other molecules on them, (iii) effective delivery to target sites, [...] Read more.
Nanoparticles have been investigated as drug carriers, because they provide a great opportunity due to their advantageous features: (i) various formulations using organic/inorganic materials, (ii) easy modification of targeting molecules, drugs or other molecules on them, (iii) effective delivery to target sites, resulting in high therapeutic efficacy and (iv) controlling drug release by external/internal stimuli. Because of these features, therapeutic efficacy can be improved and unwanted side effects can be reduced. Theranostic nanoparticles have been developed by incorporating imaging agents in drug carriers as all-in-one system, which makes it possible to diagnose and treat cancer by monitoring drug delivery behavior simultaneously. Recently, stimuli-responsive, activatable nanomaterials are being applied that are capable of producing chemical or physical changes by external stimuli. By using these nanoparticles, multiple tasks can be carried out simultaneously, e.g., early and accurate diagnosis, efficient cataloguing of patient groups of personalized therapy and real-time monitoring of disease progress. In this paper, we describe various types of nanoparticles for drug delivery systems, as well as theranostic systems. Full article
(This article belongs to the Special Issue Drug Delivery Using Nanotechnology)
Open AccessReview From Molecular to Nanotechnology Strategies for Delivery of Neurotrophins: Emphasis on Brain-Derived Neurotrophic Factor (BDNF)
Pharmaceutics 2013, 5(1), 127-167; doi:10.3390/pharmaceutics5010127
Received: 13 November 2012 / Revised: 30 January 2013 / Accepted: 5 February 2013 / Published: 8 February 2013
Cited by 18 | PDF Full-text (809 KB) | HTML Full-text | XML Full-text
Abstract
Neurodegenerative diseases represent a major public health problem, but beneficial clinical treatment with neurotrophic factors has not been established yet. The therapeutic use of neurotrophins has been restrained by their instability and rapid degradation in biological medium. A variety of strategies has [...] Read more.
Neurodegenerative diseases represent a major public health problem, but beneficial clinical treatment with neurotrophic factors has not been established yet. The therapeutic use of neurotrophins has been restrained by their instability and rapid degradation in biological medium. A variety of strategies has been proposed for the administration of these leading therapeutic candidates, which are essential for the development, survival and function of human neurons. In this review, we describe the existing approaches for delivery of brain-derived neurotrophic factor (BDNF), which is the most abundant neurotrophin in the mammalian central nervous system (CNS). Biomimetic peptides of BDNF have emerged as a promising therapy against neurodegenerative disorders. Polymer-based carriers have provided sustained neurotrophin delivery, whereas lipid-based particles have contributed also to potentiation of the BDNF action. Nanotechnology offers new possibilities for the design of vehicles for neuroprotection and neuroregeneration. Recent developments in nanoscale carriers for encapsulation and transport of BDNF are highlighted. Full article
(This article belongs to the Special Issue Drug Delivery Using Nanotechnology)
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Open AccessReview Protein Adsorption Patterns and Analysis on IV Nanoemulsions—The Key Factor Determining the Organ Distribution
Pharmaceutics 2013, 5(1), 36-68; doi:10.3390/pharmaceutics5010036
Received: 1 November 2012 / Revised: 30 November 2012 / Accepted: 4 December 2012 / Published: 21 December 2012
Cited by 9 | PDF Full-text (1293 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Intravenous nanoemulsions have been on the market for parenteral nutrition since the 1950s; meanwhile, they have also been used successfully for IV drug delivery. To be well tolerable, the emulsions should avoid uptake by the MPS cells of the body; for drug [...] Read more.
Intravenous nanoemulsions have been on the market for parenteral nutrition since the 1950s; meanwhile, they have also been used successfully for IV drug delivery. To be well tolerable, the emulsions should avoid uptake by the MPS cells of the body; for drug delivery, they should be target-specific. The organ distribution is determined by the proteins adsorbing them after injection from the blood (protein adsorption pattern), typically analyzed by two-dimensional polyacrylamide gel electrophoresis, 2-D PAGE. The article reviews the 2-D PAGE method, the analytical problems to be faced and the knowledge available on how the composition of emulsions affects the protein adsorption patterns, e.g., the composition of the oil phase, stabilizer layer and drug incorporation into the interface or oil core. Data were re-evaluated and compared, and the implications for the in vivo distribution are discussed. Major results are that the interfacial composition of the stabilizer layer is the main determining factor and that this composition can be modulated by simple processes. Drug incorporation affects the pattern depending on the localization of the drug (oil core versus interface). The data situation regarding in vivo effects is very limited; mainly, it has to be referred to in the in vivo data of polymeric nanoparticles. As a conclusion, determination of the protein adsorption patterns can accelerate IV nanoemulsion formulation development regarding optimized organ distribution and related pharmacokinetics. Full article
(This article belongs to the Special Issue Drug Delivery Using Nanotechnology)

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