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Effective drug delivery in pancreatic cancer treatment remains a major challenge. Because of the high resistance to chemo and radiation therapy, the overall survival rate for pancreatic cancer is extremely low. Recent advances in drug delivery systems hold great promise for improving cancer therapy. Using liposomes, nanoparticles, and carbon nanotubes to deliver cancer drugs and other therapeutic agents such as siRNA, suicide gene, oncolytic virus, small molecule inhibitor, and antibody has been a success in recent preclinical trials. However, how to improve the specificity and stability of the delivered drug using ligand or antibody directed delivery represent a major problem. Therefore, developing novel, specific, tumor-targeted drug delivery systems is urgently needed for this terrible disease. This review summarizes the current progress on targeted drug delivery in pancreatic cancer and provides important information on potential therapeutic targets for pancreatic cancer treatment. 相似文献
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Smith NB 《International journal of nanomedicine》2007,2(4):585-594
The use of needles for multiple injection of drugs, such as insulin for diabetes, can be painful. As a result, prescribed drug noncompliance can result in severe medical complications. Several noninvasive methods exist for transdermal drug delivery. These include chemical mediation using liposomes and chemical enhancers or physical mechanisms such as microneedles, iontophoresis, electroporation, and ultrasound. Ultrasound enhanced transdermal drug delivery offers advantages over traditional drug delivery methods which are often invasive and painful. A broad review of the transdermal ultrasound drug delivery literature has shown that this technology offers promising potential for noninvasive drug administration. From a clinical perspective, few drugs, proteins or peptides have been successfully administered transdermally because of the low skin permeability to these relatively large molecules, although much work is underway to resolve this problem. The proposed mechanism of ultrasound has been suggested to be the result of cavitation, which is discussed along with the bioeffects from therapeutic ultrasound. For low frequencies, potential transducers which can be used for drug delivery are discussed, along with cautions regarding ultrasound safety versus efficacy. 相似文献
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Beom Soo Kim In Duck Jung Jong Sik Kim Jung-heon Lee In Young Lee Kyung Bok Lee 《Biotechnology letters》2000,22(14):1127-1130
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). 相似文献
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Bal Ram Singh Nagarajan Thirunavukkarasu Koyel Ghosal Easwaran Ravichandran Roshan Kukreja Shuowei Cai Peng Zhang Radharaman Ray Prabhati Ray 《Biochimie》2010
Several neuronal disorders require drug treatment using drug delivery systems for specific delivery of the drugs for the targeted tissues, both at the peripheral and central nervous system levels. We describe a review of information currently available on the potential use of appropriate domains of clostridial neurotoxins, tetanus and botulinum, for effective drug delivery to neuronal systems. While both tetanus and botulinum neurotoxins are capable of delivering drugs the neuronal cells, tetanus neurotoxin is limited in clinical use because of general immunization of population against tetanus. Botulinum neurotoxin which is also being used as a therapeutic reagent has strong potential for drug delivery to nervous tissues. 相似文献
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The treatment for many neurodegenerative diseases of the central nervous system (CNS) involves the delivery of large molecular weight drugs to the brain. The blood brain barrier, however, prevents many therapeutic molecules from entering the CNS. Despite much effort in studying drug dispersion with animal models, accurate drug targeting in humans remains a challenge. This article proposes an engineering approach for the systematic design of targeted drug delivery into the human brain. The proposed method predicts achievable volumes of distribution for therapeutic agents based on first principles transport and chemical kinetics models as well as accurate reconstruction of the brain geometry from patient-specific diffusion tensor magnetic resonance imaging. The predictive capabilities of the methodology will be demonstrated for invasive intraparenchymal drug administration. A systematic procedure to determine the optimal infusion and catheter design parameters to maximize penetration depth and volumes of distribution in the target area will be discussed. The computational results are validated with agarose gel phantom experiments. The methodology integrates interdisciplinary expertise from medical imaging and engineering. This approach will allow physicians and scientists to design and optimize drug administration in a systematic fashion. 相似文献
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Allan S. Hoffman Patrick S. Stayton Oliver Press Niren Murthy Chantal A. Lackey Charles Cheung Fiona Black Jean Campbell Nelson Fausto Themis R. Kyriakides Paul Bornstein 《Biotechnology and Bioprocess Engineering》2001,6(4):205-212
One of the important characteristics of biological systems is their ability to change important properties in response to
small environmental signals. The molecular mechanisms that biological molecules utilize to sense and respond provide interesting
models for the development of “smart” polymeric biomaterials with biomimetic properties. An important example of this is the
protein coat of viruses, which contains peptide units that facilitate the trafficking of the virus into the cell via endocytosis,
then out of the endosome into the cytoplasm, and from there into the nucleus. We have designed a family of synthetic polymers
whose compositions have been designed to mimic specific peptides on viral coats that facilitate endosomal escape. Our biomimetic
polymers are responsive to the lowered pH within endosomes, leading to disruption of the endosomal membrane and release of
important biomolecular drugs such as DNA, RNA, peptides and proteins to the cytoplasm before they are trafficked to lysosomes
and degraded by lysosomal enzymes. In this article, we review our work on the design, synthesis and action of such smart,
pH-sensitive polymers. 相似文献
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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. 相似文献
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Priscileila C. Ferrari Giselle F. Oliveira Flvia Cristina S. Chibebe Raul C. Evangelista 《Carbohydrate polymers》2009,78(3):557-563
A relative simple drug delivery system in the form of coevaporates were prepared and analyzed. They were based on chitosan (CS), a polysaccharide that undergoes specific degradation by colonic enzymes. Enteric polymers, namely cellulose acetate phtalate (CAP) and hydroxypropylmethylcellulose phtalate (HPMCP), were incorporated, due to their insolubility in environments presenting low pH values. The systems were physically characterized, demonstrating that CS affects the swelling properties of the samples. The ability of these systems to reach the colonic region was assessed in vitro in simulated gastric, enteric and colonic fluids. Korsmeyer–Peppas and Weibull models were applied to analyze the drug release kinetics and the results suggested that the drug release from the coevaporates follows a complex release mechanism, in which several processes, including diffusion, swelling, and erosion, are involved and may occur simultaneously. The results demonstrated that it is possible to prepare relative simple drug carrier systems able to reach the colonic environment, since their swelling capacity can be controlled by varying the composition. 相似文献
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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. 相似文献
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R. Caillard A. Petit M. Subirade 《International journal of biological macromolecules》2009,45(4):414-420
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. 相似文献
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The purpose of writing this review on floating drug delivery systems (FDDS) was to compile the recent literature with special
focus on the principal mechanism of floatation to achieve gastric retention. The recent developments of FDDS including the
physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating
systems, and their classification and formulation aspects are covered in detail. This review also summarizes the in vitro
techniques, in vivo studies to evaluate the performance and application of floating systems, and applications of these systems.
These systems are useful to several problems encountered during the development of a pharmaceutical dosage form.
Published: October 19, 2005 相似文献
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Farnaz Assa Hossein Ajamein Hamideh Vaghari Omid Ahmadi 《Critical reviews in biotechnology》2017,37(4):492-509
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. 相似文献
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The purpose of this research was to prepare a gastroretentive drug delivery system of ranitidine hydrochloride. Guar gum,
xanthan gum, and hydroxypropyl methylcellulose were evaluated for gel-forming properties. Sodium bicarbonate was incorporated
as a gas-generating agent. The effects of citric acid and stearic acid on drug release profile and floating properties were
investigated. The addition of stearic acid reduces the drug dissolution due to its hydrophobic nature. A 32 full factorial design was applied to systemically optimize the drug release profile. The amounts of citric acid anhydrous
(X1) and stearic acid (X2) were selected as independent variables. The times required for 50% (t50) and 80% drug dissolution (t80), and the similarity factor f2 were selected as dependent variables. The results of the full factorial design indicated that a low amount of citric acid
and a high amount of stearic acid favors sustained release of ranitidine hydrochloride from a gastroretentive formulation.
A theoretical dissolution profile was generated using pharmacokinetic parameters of ranitidine hydrochloride. The similarity
factor f2 was applied between the factorial design batches and the theoretical dissolution profile. No significant difference was observed
between the desired release profile and batches F2, F3, F6, and F9. Batch F9 showed the highest f2 (f2=75) among all the batches,
and this similarity is also reflected in t50 (∼214 minutes) and t80 (∼537 minutes) values. These studies indicate that the proper balance between a release rate enhancer and a release rate
retardant can produce a drug dissolution profile similar to a theoretical dissolution profile. 相似文献
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Cancer chemotherapy is mainly based on the use of cytotoxic compounds that often affect other tissues, generating serious side effects which deteriorate the quality of life of patients. Recent advancements in targeted drug delivery systems offer opportunities to improve the efficiency of chemotherapy, by the use of smaller drug doses with reduced side effects. In the gene therapy approach, this consists in improving the transformation potential of the gene delivery system. Interestingly, these systems further provide good platforms for the delivery of hydrophobic and low-bioavailability compounds, while facilitating the penetration of the blood-brain barrier. The present report provides an overview of biologically relevant cancer hallmarks that can be exploited to design effective delivery vehicles that release cytotoxic compounds specifically in cancer tissues, in a targeted manner. The relevance of each cancer marker is presented, with particular emphasis on the generation of these hallmarks and their importance in cancer cell biology. 相似文献
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《Journal of liposome research》2013,23(2):128-138
One of the greatest challenges in in situ forming implant (ISFI) systems by polymer precipitation is the large burst release during the first 1–24 hours after implant injection. The aim of this study was to decrease the burst-release effect of a water-soluble model drug, donepezil HCl, with a molecular weight of 415.96?Da, from in situ forming implants using a novel in situ implant containing lipospheres (ISILs). In situ implant suspensions were prepared by dispersing cetyl alcohol and glyceryl stearate lipospheres in a solution of poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG). Also, in situ implant solutions were prepared using different concentrations of PDL or PDLG solutions in N-methyl-2-pyrrolidone (NMP). Triacetin and Pluronic L121 were used to modify the release pattern of donepezil from the in situ implant solutions. In vitro release, rheological measurement, and injectability measurement were used to evaluate the prepared in situ implant formulae. It was found that ISIL decreased the burst effect as well as the rate and extent of drug release, compared to lipospheres, PDL, and PDLG in situ implant. The amount of drug released in the first day was 37.75, 34.99, 48.57, 76.3, and 84.82% for ISIL in 20% PDL (IL-1), ISIL in 20% PDLG (IL-2), lipospheres (L), 20% PDL ISFI (I5), and 20% PDLG ISFI (I8), respectively. The prepared systems showed Newtonian flow behavior. ISIL (IL-1 and IL-2) had a flow rate of 1.94 and 1.40?mL/min, respectively. This study shows the potential of using in situ implants containing lipospheres in controlling the burst effect of ISFI. 相似文献
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Kejík Z Bříza T Králová J Poučková P Král A Martásek P Král V 《Bioorganic & medicinal chemistry letters》2011,21(18):5514-5520
We present here a general system for the coordination attachment of therapeutic proteins to a drug delivery system and its application in combined therapy. Proof of concept is demonstrated by the synthesis and testing of the targeted drug delivery system for cytostatics, which is based on a combination of the drug carrier Zn-porphyrin-cyclodextrin conjugates and their supramolecular coordination complexes with immunoglobulins. This system can be as readily used for a variety of therapeutic and targeting proteins including PAs, MAs, lectins, and HSA. Moreover, it allows combined photodynamic therapy, cell targeted chemotherapy and immunotherapy. When tested in a mouse model with human C32 carcinoma, the therapeutic superiority of the coordination assembly nanosystem was shown in comparison with the efficacy of building blocks used for the construction of the system. 相似文献