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1

Preparation and characterization of biocompatible and thermoresponsive micelles based on poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) grafted on polysuccinimide for drug delivery.  

PubMed

Biocompatible and temperature-sensitive amphiphilic polymeric micelles comprised of poly(succinimide)-g-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PSI-g-poly(NIPAAm-co-DMAAm)) were synthesized to use as new drug carriers. The PSI-co-poly(PNIPAAm-co-DMAAm) polymers were prepared by nucleophilic opening of poly(succinimide) using amino-terminated poly(NIPAAm-co-DMAAm). The lower critical solution temperature of the copolymer was 40.6? higher than normal human body temperature. The blank polymeric micelles were observed to have a regular spherical shape, and the particle sizes were approximately 85?nm. This copolymer exhibited no significant cytotoxicity and hemolysis indicated that the micelles had good biocompatibility. In addition, these polymeric micelles encapsulated the anti-inflammatory drug, hesperetin, in the inner core with a drug loading content of approximately 20%. The release profiles of hesperetin showed a significant temperature-sensitive switching behavior. The hesperetin release response was dramatically lower at a temperature below the lower critical solution temperature as compared with a temperature above the lower critical solution temperature. The lipopolysaccharide-induced nitric oxide production inhibition experiments demonstrated that hesperetin-encapsulated micelles showed a significant reduction. In this study, the biocompatible temperature-sensitive micelles based on PSI-g-poly(NIPAAm-co-DMAAm) have great potential to act as a suitable carrier for drug delivery. PMID:24825758

Yeh, Jih-Chao; Hsu, Ya-Ting; Su, Chao-Ming; Wang, Ming-Chen; Lee, Tsong-Hai; Lou, Shyh-Liang

2014-09-01

2

Micelles based on methoxy poly(ethylene glycol)-cholesterol conjugate for controlled and targeted drug delivery of a poorly water soluble drug.  

PubMed

In this study, quercetin (QC) with cancer chemoprevention effect and anticancer potential was loaded into polymeric micelles of methoxy poly(ethylene glycol)-cholesterol conjugate (mPEG-Chol) in order to increase its water solubility. MPEG-Chol with lower critical micelle concentration (CMC) value (4.0 x 10(-7) M - 13 x 10(-7) M) was firstly synthesized involving two steps of chemical modification on cholesterol by esterification, and then QC was incorporated into mPEG-Chol micelles by self-assembly method. After the process parameters were optimized, QC-loaded micelles had higher drug loading (3.66%) and entrapment efficiency (93.51%) and nano-sized diameter (116 nm). DSC analysis demonstrated that QC had been incorporated non-covalently into the micelles and existed as an amorphous state or a solid solution in the polymeric matrix. The freeze-dried formulation with addition of 1% (w/v) mannitol as cryoprotectant was successfully developed for the long-term storage of QC-loaded micelles. Compared to free QC, QC-loaded micelles could release QC more slowly. Moreover, the release of QC from micelles was slightly faster in PBS at pH 5 than that in PBS at pH 7.4, which implied that QC-loaded micelles might be pH-sensitive and thereby selectively deliver QC to tumor tissue with unwanted side effects. Therefore, mPEG-Chol was a promising micellar vector for the controlled and targeted drug delivery of QC to tumor and QC-loaded micelles were also worth being further investigated as a potential formulation for cancer chemoprevention and treatment. PMID:22888752

Li, Junming; He, Zhiyao; Yu, Shui; Li, Shuangzhi; Ma, Qing; Yu, Yiyi; Zhang, Jialin; Li, Rui; Zheng, Yu; He, Gu; Song, Xiangrong

2012-10-01

3

Self-assembled micelles based on pH-sensitive PAE-g-MPEG-cholesterol block copolymer for anticancer drug delivery  

PubMed Central

A novel amphiphilic triblock pH-sensitive poly(?-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol (PAE-g-MPEG-Chol) was designed and synthesized via the Michael-type step polymerization and esterification condensation method. The synthesized copolymer was determined with proton nuclear magnetic resonance and gel permeation chromatography. The grafting percentages of MPEG and cholesterol were determined as 10.93% and 62.02%, calculated from the area of the characteristic peaks, respectively. The amphiphilic copolymer was confirmed to self-assemble into core/shell micelles in aqueous solution at low concentrations. The critical micelle concentrations were 6.92 and 15.14 mg/L at pH of 7.4 and 6.0, respectively, obviously influenced by the changes of pH values. The solubility of pH-responsive PAE segment could be transformed depending on the different values of pH because of protonation–deprotonation of the amino groups, resulting in pH sensitivity of the copolymer. The average particle size of micelles increased from 125 nm to 165 nm with the pH decreasing, and the zeta potential was also significantly changed. Doxorubicin (DOX) was entrapped into the polymeric micelles with a high drug loading level. The in vitro DOX release from the micelles was distinctly enhanced with the pH decreasing from 7.4 to 6.0. Toxicity testing proved that the DOX-loaded micelles exhibited high cytotoxicity in HepG2 cells, whereas the copolymer showed low toxicity. The results demonstrated how pH-sensitive PAE-g-MPEG-Chol micelles were proved to be a potential vector in hydrophobic drug delivery for tumor therapy. PMID:25364250

Zhang, Can Yang; Xiong, Di; Sun, Yao; Zhao, Bin; Lin, Wen Jing; Zhang, Li Juan

2014-01-01

4

Reduction-responsive core-shell-corona micelles based on triblock copolymers: novel synthetic strategy, characterization, and application as a tumor microenvironment-responsive drug delivery system.  

PubMed

A facile and effective approach was established for fabricating core-shell-corona micelles by self-assembly of poly(ethylene glycol)-b-poly(acrylic acid-co-tert-butyl acrylate)-poly(?-caprolactone) (PEG43-b-P(AA30-co-tBA18)-b-PCL53) triblock copolymer, synthesized via a combination of ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP), click chemistry, and hydrolyzation. The prenanovehicles with three different hydrolysis degrees from PEG43-b-PtBA48-b-PCL53 were developed to evaluate the drug loading capacity (DLC) and drug encapsulation efficiency (DEE). After cross-linking with a disulfide bond to regulate the drug release kinetics, the spherical core-shell-corona micelles with average diameter of 52 ± 4 nm were obtained in aqueous solution. The reduction-responsive cross-linked micelles showed a slow sustained release in normal physiological conditions and a rapid release upon exposure to simulated tumor intracellular conditions. In addition, the cytotoxic analysis and HepG2 cell growth inhibition assays demonstrated their remarkable biocompatibility and similar excellent anticancer activity as the free doxorubicin (DOX), which has also been revealed by the confocal laser scanning microscope (CLSM) analysis. So the reduction-sensitive core-shell-corona micelles are expected to be promising tumor microenvironment-responsive nanovehicles for hydrophobic drugs by glutathione (GSH) triggering. PMID:25394962

Zhao, Xubo; Liu, Peng

2015-01-14

5

Communications Drug Delivery  

E-print Network

Communications Drug Delivery Z. Zhao, H. Meng, N. Wang, M. J. Donovan, T. Fu, M. You, Z. Chen, X Targeting and Translocation for Drug Delivery This pHLIP is no flop: Functionalizing mesoporous silica nanoparticles (MSNs) with pHLIPss peptide provides a con- trolled-release nanoparticle drug delivery system

Tan, Weihong

6

Transdermal drug delivery  

PubMed Central

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

Prausnitz, Mark R.; Langer, Robert

2009-01-01

7

Doxorubicin loaded singlet-oxygen producible polymeric micelle based on chlorine e6 conjugated pluronic F127 for overcoming drug resistance in cancer.  

PubMed

Drug resistance remains one of the primary obstacles to the success of cancer chemotherapy. In this work, we demonstrate a singlet-oxygen producible polymeric (SOPP) micelle based on photosensitizer (PS, chlorin e6 (Ce6)) conjugated amphiphilic copolymer (pluronic F127(®), PF127) for overcoming drug resistance in cancer by applying photochemical internalization (PCI). The doxorubicin (DOX)-loaded SOPP micelles were self-assembled from Ce6-PF127 conjugates, which have a spherical shape with a uniform size of ?30 nm. Compared with free Ce6, enhanced singlet-oxygen generation efficiency in the DOX-loaded SOPP micelles have been demonstrated in aqueous environments due to their increased water-dispersibility. Under low dose of laser power and anti-cancer drug (DOX) conditions, in vitro and in vivo studies on drug-resistant cancer cells demonstrated that singlet-oxygen-mediated cellular membrane damage (caused by lipid peroxidation) significantly increased the cellular uptake of drug (DOX), which led to overcoming the drug resistance in cancer cells without undesirable side effects. We believe this approach could represent a promising platform for drug-resistant cancer treatment. PMID:24934645

Park, Hyung; Park, Wooram; Na, Kun

2014-09-01

8

Drug delivery Combinatorial Drug Conjugation Enables Nanoparticle  

E-print Network

Drug delivery Combinatorial Drug Conjugation Enables Nanoparticle Dual-Drug Delivery Santosh Aryal, Che-Ming Jack Hu, and Liangfang Zhang* A new approach to loading multiple drugs onto the same drug through hydrolyzable linkers to form drug conjugates, is reported. In contrast to loading individual types

Zhang, Liangfang

9

Drug Formulation / Drug Delivery Raj Suryanarayanan (Sury)  

E-print Network

Drug Formulation / Drug Delivery Raj Suryanarayanan (Sury) Department of Pharmaceutics College)Physical Pharmaceutics (Materials Science) Suryanarayanan, Sun Drug Delivery K di ll P bh P Si l Wi dKandimalla, Prabha, Panyam, Siegel, Wiedmann 2 #12;#12;Center for Translational Drug Delivery Developing

Blanchette, Robert A.

10

Cyclodextrins in nasal drug delivery  

Microsoft Academic Search

Nasal drug delivery is an attractive approach for the systemic delivery of high potency drugs with a low oral bioavailability due to extensive gastrointestinal breakdown and high hepatic first-pass effect. For lipophilic drugs nasal delivery is possible if they can be dissolved in the dosage form. Peptide and protein drugs often have a low nasal bioavailability because of their large

F. W. H. M Merkus; J. C Verhoef; E Marttin; S. G Romeijn; P. H. M van der Kuy; W. A. J. J Hermens; N. G. M Schipper

1999-01-01

11

Microprocessor controlled transdermal drug delivery.  

PubMed

Transdermal drug delivery via iontophoresis is reviewed with special focus on the delivery of lidocaine for local anesthesia and fentanyl for patient controlled acute therapy such as postoperative pain. The role of the microprocessor controller in achieving dosimetry, alternating/reverse polarity, pre-programmed, and sensor-based delivery is highlighted. Unique features such as the use of tactile signaling, telemetry control, and pulsatile waveforms in iontophoretic drug delivery are described briefly. PMID:16713690

Subramony, J Anand; Sharma, Ashutosh; Phipps, J B

2006-07-01

12

New Methods of Drug Delivery  

Microsoft Academic Search

Conventional forms of drug administration generally rely on pills, eye drops, ointments, and intravenous solutions. Recently, a number of novel drug delivery approaches have been developed. These approaches include drug modification by chemical means, drug entrapment in small vesicles that are injected into the bloodstream, and drug entrapment within pumps or polymeric materials that are placed in desired bodily compartments

Robert Langer

1990-01-01

13

Cell-Mediated Drugs Delivery  

PubMed Central

INTRODUCTION Drug targeting to sites of tissue injury, tumor or infection with limited toxicity is the goal for successful pharmaceutics. Immunocytes (including mononuclear phagocytes (dendritic cells, monocytes and macrophages), neutrophils, and lymphocytes) are highly mobile; they can migrate across impermeable barriers and release their drug cargo at sites of infection or tissue injury. Thus immune cells can be exploited as trojan horses for drug delivery. AREAS COVERED IN THIS REVIEW This paper reviews how immunocytes laden with drugs can cross the blood brain or blood tumor barriers, to facilitate treatments for infectious diseases, injury, cancer, or inflammatory diseases. The promises and perils of cell-mediated drug delivery are reviewed, with examples of how immunocytes can be harnessed to improve therapeutic end points. EXPERT OPINION Using cells as delivery vehicles enables targeted drug transport, and prolonged circulation times, along with reductions in cell and tissue toxicities. Such systems for drug carriage and targeted release represent a novel disease combating strategy being applied to a spectrum of human disorders. The design of nanocarriers for cell-mediated drug delivery may differ from those used for conventional drug delivery systems; nevertheless, engaging different defense mechanisms into drug delivery may open new perspectives for the active delivery of drugs. PMID:21348773

Batrakova, Elena V.; Gendelman, Howard E.; Kabanov, Alexander V.

2011-01-01

14

PECTIN BASED DRUG DELIVERY SYSTEMS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Two drug delivery systems have been developed from pectin recently in our laboratory. (I) Pectin gel formulations for controlled fragrance release and (II) pectin/zein hydrogels for oral drug delivery. By altering the molecular characteristics or modifying the pectin hydrogel networks, the release ...

15

Microneedles for transdermal drug delivery  

Microsoft Academic Search

The success of transdermal drug delivery has been severely limited by the inability of most drugs to enter the skin at therapeutically useful rates. Recently, the use of micron-scale needles in increasing skin permeability has been proposed and shown to dramatically increase transdermal delivery, especially for macromolecules. Using the tools of the microelectronics industry, microneedles have been fabricated with a

Mark R Prausnitz

2004-01-01

16

Advances in ophthalmic drug delivery.  

PubMed

Various strategies for ocular drug delivery are considered; from basic formulation techniques for improving availability of drugs; viscosity enhancers and mucoadhesives aid drug retention and penetration enhancers promote drug transport into the eye. The use of drug-loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for more direct delivery. Developments in ocular implants gives a means to overcome the physical barriers that traditionally prevented effective treatment. Implant technologies are under development allowing long-term drug delivery from a single procedure, these devices allow posterior chamber diseases to be effectively treated. Future developments could bring artificial corneas to eliminate the need for donor tissue and one-off implantable drug depots lasting the patient's lifetime. PMID:25531930

Morrison, Peter Wj; Khutoryanskiy, Vitaliy V

2014-12-01

17

Drug delivery to the ear.  

PubMed

Drug delivery to the ear is used to treat conditions of the middle and inner ear such as acute and chronic otitis media, Ménière's disease, sensorineural hearing loss and tinnitus. Drugs used include antibiotics, antifungals, steroids, local anesthetics and neuroprotective agents. A literature review was conducted searching Medline (1966-2012), Embase (1988-2012), the Cochrane Library and Ovid (1966-2012), using search terms 'drug delivery', 'middle ear', 'inner ear' and 'transtympanic'. There are numerous methods of drug delivery to the middle ear, which can be categorized as topical, systemic (intravenous), transtympanic and via the Eustachian tube. Localized treatments to the ear have the advantages of targeted drug delivery allowing higher therapeutic doses and minimizing systemic side effects. The ideal scenario would be a carrier system that could cross the intact tympanic membrane loaded with drugs or biochemical agents for the treatment of middle and inner ear conditions. PMID:23323784

Hoskison, E; Daniel, M; Al-Zahid, S; Shakesheff, K M; Bayston, R; Birchall, J P

2013-01-01

18

Bioresponsive matrices in drug delivery  

PubMed Central

For years, the field of drug delivery has focused on (1) controlling the release of a therapeutic and (2) targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli. PMID:21114841

2010-01-01

19

Synthesis and optimization of a novel polymeric micelle based on hyaluronic acid and phospholipids for delivery of paclitaxel, in vitro and in-vivo evaluation.  

PubMed

Novel polymeric micelles were synthesized based on hyaluronic acid (HA) and phospholipids (PEs) including 1,2-dimiristoyl phosphatidylethanolamine (DMPE) and 1,2-distearoyl phosphatidylethanolamine (DSPE). The newly developed micelles evaluated for the physicochemical properties including structural analysis by means of FTIR. Micelles were optimized for delivery of paclitaxel (PTX). The D-optimal design was applied in order to reach micelles with high entrapment efficiency (EE %) and minimum size, simultaneously. In this design the independent variables were the co-polymer type, the drug to polymer ratio and the formulation temperature, whereas the dependent variables were EE% and micelle size. The EE% of the optimized micelles was 46.8% and 59.9% for HA-DMPE and HA-DSPE micelles, respectively. The size of the optimized micelles was in the range of around 250nm. In vitro release study of the optimized micelles showed that PTX was released from HA-DMPE and HA-DSPE micelles as long as 23h and 34h, respectively. Differential scanning calorimetry (DSC) studies showed a conversion of the crystalline PTX molecules into the amorphous form in the micelles. In vivo real time image analysis showed that micellar system was mostly accumulated in the liver, spleen and heart. Accelerated stability studies represented that PTX loaded micelle formulations were stable both physically and chemically at least in 6 months' time. PMID:25148729

Saadat, Ebrahim; Amini, Mohsen; Khoshayand, Mohammad Reza; Dinarvand, Rassoul; Dorkoosh, Farid A

2014-11-20

20

Effective drug delivery by PEGylated drug conjugates  

Microsoft Academic Search

The current review presents an update of drug delivery using poly(ethylene glycol) (PEG), that focuses on recent developments in both protein and organic drugs. Certainly the past 10 years has resulted in a renaissance of the field of PEG drug conjugates, initiated by the use of higher molecular weight PEGs (Mw>20,000), especially 40,000 which is estimated to have a plasma

Richard B. Greenwald; Yun H. Choe; Jeffrey McGuire; Charles D. Conover

2003-01-01

21

Macromolecules in drug delivery Macromolecular targeting agents, carriers, and drugs  

E-print Network

Macromolecules in drug delivery Macromolecular targeting agents, carriers, and drugs 1gauthier@emt.inrs.ca #12;Why macromolecules in drug delivery? 2gauthier@emt.inrs.ca Classic chemotherapy Drug delivery? Targeting A carrier for small drugs A release mechanism (if necessary) Protection of drug cargo #12;How? 3

Barthelat, Francois

22

Recent developments in drug delivery.  

PubMed

Some recent innovative approaches to drug delivery have demonstrated that the administration of drugs can be more rigidly controlled with respect to the rate and amount of drug delivered to sites of action than from the conventional dosage forms. One category of controlled release referred to as programmed drug delivery primarily involves the application of polymers of defined specifications to release agents from either non-bioerodible membrane-controlled systems or bioerodible and non-bioerodible matrices. Also included here are the pro-drugs, inactive derivatives of drugs which are transformed into the active form in vivo but possess improved solubility, stability and disposition properties, yielding more efficient action and fewer side effects. Thus, exploitation of several routes of administration have resulted in products which are inserted ophtalmically, rectally or vaginally, implanted subcutaneously, taken orally or applied topically to achieve transdermal delivery of drugs to the systemic circulation. In several cases, release is designed to follow zero-order kinetics to achieve control of therapeutic plasma concentrations for prolonged time periods. Targeting of drugs by carrier is another form of controlled release technology. Normally administered intravenously, carriers such as liposomes, nanoparticles, microspheres, human cells and linear macromolecules are finding application in treating disease states with drugs which previously were unavailable to treatment. PMID:10262189

Rogers, J A

1982-01-01

23

Transmucosal macromolecular drug delivery  

Microsoft Academic Search

Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and\\/or are degraded before reaching the blood stream. Among the approaches explored so far in order to optimize the transport of these macromolecules across mucosal barriers, the use of nanoparticulate

C. Prego; M. García; D. Torres; M. J. Alonso

2005-01-01

24

Iontophoretic drug delivery  

Microsoft Academic Search

The composition and architecture of the stratum corneum render it a formidable barrier to the topical and transdermal administration of therapeutic agents. The physicochemical constraints severely limit the number of molecules that can be considered as realistic candidates for transdermal delivery. Iontophoresis provides a mechanism to enhance the penetration of hydrophilic and charged molecules across the skin. The principal distinguishing

Yogeshvar N. Kalia; Aarti Naik; James Garrison; Richard H. Guy

2004-01-01

25

Aptamers as drug delivery vehicles.  

PubMed

The benefits of directed and selective therapy for systemic treatment are reasons for increased interest in exploiting aptamers for cell-specific drug delivery. Nucleic acid based pharmaceuticals represent an interesting and novel tool to counter human diseases. Combining inhibitory potential and cargo transfer upon internalization, nanocarriers as well as various therapeutics including siRNAs, chemotherapeutics, photosensitizers, or proteins can be imported via these synthetic nucleic acids. However, widespread clinical application is still hampered by obstacles that must be overcome. In this review, we give an overview of applications and recent advances in aptamer-mediated drug delivery. We also introduce prominent selection methods as well as useful approaches in choice of drug and conjugation method. We discuss the challenges that need to be considered and present strategies that have been applied to achieve intracellular delivery of effectors transported by readily internalized aptamers. PMID:25130604

Kruspe, Sven; Mittelberger, Florian; Szameit, Kristina; Hahn, Ulrich

2014-09-01

26

Micelles based on HPMA copolymers.  

PubMed

Polymeric micelles have been under extensive investigation during the past years as drug delivery systems, particularly for anticancer drugs. They are formed by the self-assembly of amphiphilic block copolymers in aqueous solutions and have a spherical shape and a size in the nano-range (<200nm). Tumor accumulation of polymeric micelles upon intravenous administration can occur as a result of the leaky vasculature of tumor tissue (called the enhanced permeation and retention (EPR) effect).To benefit from the EPR effect, polymeric micelles need to have prolonged circulation times as well as high and stable drug loadings. Poly[N-(2-hydroxypropyl) methacrylamide] (pHPMA) is a hydrophilic polymer currently under investigation for its use in polymer-drug conjugates. Its biocompatibility, non-immunogenicity and the possibility for functionalization are properties that resulted in broad pharmaceutical and biomedical applications, also in the micelle technology research. Being hydrophilic, it can serve as a micellar stealth corona, while it can also be modified with hydrophobic moieties to serve as a micellar core in which hydrophobic drugs can be solubilized and retained. HPMA-based polymeric micelles have been showing very promising in vitro and in vivo results. This review summarizes the applications of pHPMA in the field of polymeric micelles, either serving as a micellar stealth corona, or, if hydrophobically rendered by derivatization, as a micellar core. PMID:20004693

Talelli, M; Rijcken, C J F; van Nostrum, C F; Storm, G; Hennink, W E

2010-02-17

27

Nanocarriers and Drug Delivery  

Microsoft Academic Search

Nanoparticles may serve, among other techniques, as a useful tool for achieving the main objective of regional cancer therapy:\\u000a they can deliver a higher concentration of the agent to the tumor and expose the tumor to active drug for longer periods than\\u000a safely possible with conventional formulations. These carriers combine many advantages, such as a potential for selective\\u000a targeting and

Svetlana Gelperina

28

CCMR: Drug Delivery Using Nanoparticles  

NSDL National Science Digital Library

Safe and nontoxic drug delivery is an ongoing area of research. Some current methods of drug delivery include the use of nanoparticles, hydrogels, dendrimers, and micelles. Nanoparticles can be used as vehicles in which to transport certain drugs to cancerous cells. A certain class of nanoparticles called clays is especially useful in synthesizing these drug delivery vehicles. Layered Double Hydroxides (LDHs) are a type of hydrotalcite clay with a structure similar to smectite clays. They have a general structure that consists of layers of metal hydroxides connected to a layer of another metal hydroxide by hydrogen bonding. LDHs are made up of layers of a trivalent and a divalently charged cation coordinated by six oxygen atoms. The resulting structure consists of two-dimensional sheets with positively charged faces and negatively charged edges that are stacked together via hydrogen bonding between hydroxyl groups on adjacent sheets. These sheets generally have a very high aspect ratio, resulting in a large surface area. The positively charged layers are balanced by the presence of anions between them. A wide variety of LDHs can be synthesized depending on the various cations and interlayer anions used. Characterization of the LDHs themselves as well as LDHs intercalated with the drugs was performed using X-ray diffraction and TEM and SEM microscopy.

Lin, Joyce

2005-08-17

29

Packaging for a drug delivery microelectromechanical system  

E-print Network

Local drug delivery is a fast expanding field, and has been a center of attention for researchers in medicine in the last decade. Its advantages over systemic drug delivery are clear in cancer therapy, with localized tumors. ...

Ho Duc, Hong Linh, 1978-

2005-01-01

30

Microfabricated injectable drug delivery system  

DOEpatents

A microfabricated, fully integrated drug delivery system capable of secreting controlled dosages of multiple drugs over long periods of time (up to a year). The device includes a long and narrow shaped implant with a sharp leading edge for implantation under the skin of a human in a manner analogous to a sliver. The implant includes: 1) one or more micromachined, integrated, zero power, high and constant pressure generating osmotic engine; 2) low power addressable one-shot shape memory polymer (SMP) valves for switching on the osmotic engine, and for opening drug outlet ports; 3) microfabricated polymer pistons for isolating the pressure source from drug-filled microchannels; 4) multiple drug/multiple dosage capacity, and 5) anisotropically-etched, atomically-sharp silicon leading edge for penetrating the skin during implantation. The device includes an externally mounted controller for controlling on-board electronics which activates the SMP microvalves, etc. of the implant.

Krulevitch, Peter A. (Pleasanton, CA); Wang, Amy W. (Oakland, CA)

2002-01-01

31

Drug delivery Preparation of Monodisperse Biodegradable Polymer  

E-print Network

Drug delivery Preparation of Monodisperse Biodegradable Polymer Microparticles Using a Microfluidic Flow-Focusing Device for Controlled Drug Delivery Qiaobing Xu, Michinao Hashimoto, Tram T. Dang, Todd microparticles have broad utility as vehicles for drug delivery and form the basis of several therapies approved

Prentiss, Mara

32

A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery  

E-print Network

A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery Hong Chen1 the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within

Konofagou, Elisa E.

33

Protease-mediated drug delivery  

NASA Astrophysics Data System (ADS)

Drugs used in disease treatment can cause damage to both malignant and normal tissue. This toxicity limits the maximum therapeutic dose. Drug targeting is of high interest to increase the therapeutic efficacy of the drug without increasing systemic toxicity. Certain tissue abnormalities, disease processes, cancers, and infections are characterized by high levels of activity of specific extracellular and/or intracellular proteases. Abnormally high activity levels of specific proteases are present at sites of physical or chemical trauma, blood clots, malignant tumors, rheumatoid arthritis, inflammatory bowel disease, gingival disease, glomerulonerphritis, and acute pancreatitis. Abnormal protease activity is suspected in development of liver thrombosis, pulmonary emphysema, atherosclerosis, and muscular dystrophy. Inactiviating disease-associated proteases by the administration of appropriate protease inhibitors has had limited success. Instead, one could use such proteases to target drugs to treat the condition. Protease mediated drug delivery offers such a possibility. Solubilizing groups are attached to insoluble drugs via a polypeptide chain which is specifically cleavable by certian proteases. When the solubilized drug enounters the protease, the solubilizing moieties are cleaved, and the drug precipitates at the disease location. Thus, a smaller systemic dosage could result in a therapeutic drug concentration at the treatment site with less systemic toxicity.

Dickson, Eva F.; Goyan, Rebecca L.; Kennedy, James C.; Mackay, M.; Mendes, M. A. K.; Pottier, Roy H.

2003-12-01

34

Nanothermodynamics mediates drug delivery.  

PubMed

The efficiency of penetration of nanodrugs through cell membranes imposes further complexity due to nanothermodynamic and entropic potentials at interfaces. Action of nanodrugs is effective after cell membrane penetration. Contrary to diffusion of water diluted common molecular drugs, nanosize imposes an increasing transport complexity at boundaries and interfaces (e.g., cell membrane). Indeed, tiny dimensional systems brought the concept of "nanothermodynamic potential," which is proportional to the number of nanoentities in a macroscopic system, from either the presence of surface and edge effects at the boundaries of nanoentities or the restriction of the translational and rotational degrees of freedom of molecules within them. The core element of nanothermodynamic theory is based on the assumption that the contribution of a nanosize ensemble to the free energy of a macroscopic system has its origin at the excess interaction energy between the nanostructured entities. As the size of a system is increasing, the contribution of the nanothermodynamic potential to the free energy of the system becomes negligible. Furthermore, concentration gradients at boundaries, morphological distribution of nanoentities, and restriction of the translational motion from trapping sites are the source of strong entropic potentials at the interfaces. It is evident therefore that nanothermodynamic and entropic potentials either prevent or allow enhanced concentration very close to interfaces and thus strongly modulate nanoparticle penetration within the intracellular region. In this work, it is shown that nano-sized polynuclear iron (III)-hydroxide in sucrose nanoparticles have a nonuniform concentration around the cell membrane of macrophages in vivo, compared to uniform concentration at hydrophobic prototype surfaces. The difference is attributed to the presence of entropic and nanothermodynamic potentials at interfaces. PMID:25416996

Stefi, Aikaterina L; Sarantopoulou, Evangelia; Kollia, Zoe; Spyropoulos-Antonakakis, Nikolaos; Bourkoula, Athanasia; Petrou, Panagiota S; Kakabakos, Sotirios; Soras, Georgios; Trohopoulos, Panagiotis N; Nizamutdinov, Alexey S; Semashko, Vadim V; Cefalas, Alkiviadis Constantinos

2015-01-01

35

Opportunities in respiratory drug delivery.  

PubMed

A wide range of asthma and chronic obstructive pulmonary disease products are soon to be released onto the inhaled therapies market and differentiation between these devices will help them to gain market share over their competitors. Current legislation is directing healthcare towards being more efficient and cost-effective in order to continually provide quality care despite the challenges of aging populations and fewer resources. Devices and drugs that can be differentiated by producing improved patient outcomes would, therefore, be likely to win market share. In this perspective article, the current and potential opportunities for the successful delivery and differentiation of new inhaled drug products are discussed. PMID:25531928

Pritchard, John N; Giles, Rachael D

2014-12-01

36

Food, physiology and drug delivery.  

PubMed

Gastrointestinal physiology is dynamic and complex at the best of times, and a multitude of known variables can affect the overall bioavailability of drugs delivered via the oral route. Yet while the influences of food and beverage intake as just two of these variables on oral drug delivery have been extensively documented in the wider literature, specific information on their effects remains sporadic, and is not so much contextually reviewed. Food co-ingestion with oral dosage forms can mediate several changes to drug bioavailability, yet the precise mechanisms underlying this have yet to be fully elucidated. Likewise, the often detrimental effects of alcohol (ethanol) on dosage form performance have been widely observed experimentally, but knowledge of which has only moderately impacted on clinical practice. Here, we attempt to piece together the available subject matter relating to the influences of both solid and liquid foodstuffs on the gastrointestinal milieu and the implications for oral drug delivery, with particular emphasis on the behaviour of modified-release dosage forms, formulation robustness and drug absorption. Providing better insight into these influences, and exemplifying cases where formulations have been developed or modified to circumvent their associated problems, can help to appropriately direct the design of future in vitro digestive modelling systems as well as oral dosage forms resilient to these effects. Moreover, this will help to better our understanding of the impact of food and alcohol intake on normal gut behaviour and function. PMID:23612358

Varum, F J O; Hatton, G B; Basit, A W

2013-12-01

37

SMART DRUG DELIVERY AND BIONANOTECHNOLOGY Nicholas A Peppas  

E-print Network

SMART DRUG DELIVERY AND BIONANOTECHNOLOGY Nicholas A Peppas Center forBiomaterials, Drug Delivery for nanoscale structures in drug delivery. Uses such as carriers for controlled and targeted drug delivery materials [1]. We report on major new developments of recognitive drug delivery systems. Novel drug delivery

Peppas, Nicholas A.

38

Superhydrophobic materials for drug delivery  

NASA Astrophysics Data System (ADS)

Superhydrophobicity is a property of material surfaces reflecting the ability to maintain air at the solid-liquid interface when in contact with water. These surfaces have characteristically high apparent contact angles, by definition exceeding 150°, as a result of the composite material-air surface formed under an applied water droplet. Superhydrophobic surfaces were first discovered on naturally occurring substrates, and have subsequently been fabricated in the last several decades to harness these favorable surface properties for a number of emerging applications, including their use in biomedical settings. This work describes fabrication and characterization of superhydrophobic 3D materials, as well as their use as drug delivery devices. Superhydrophobic 3D materials are distinct from 2D superhydrophobic surfaces in that air is maintained not just at the surface of the material, but also within the bulk. When the superhydrophobic 3D materials are submerged in water, water infiltrates slowly and continuously as a new water-air-material interface is formed with controlled displacement of air. Electrospinning and electrospraying are used to fabricate superhydrophobic 3D materials utilizing blends of the biocompatible polymers poly(epsilon-caprolactone) and poly(caprolactone-co-glycerol monostearate) (PGC-C18). PGC-C18 is significantly more hydrophobic than PCL (contact angle of 116° versus 83° for flat materials), and further additions of PGC-C18 into electrospun meshes and electrosprayed coatings affords increased stability of the entrapped air layer. For example, PCL meshes alone (500 mum thick) take 10 days to fully wet, and with 10% or 30% PGC-C18 addition wetting rates are dramatically slowed to 60% wetted by 77 days and 4% by 75 days, respectively. Stability of the superhydrophobic materials can be further probed with a variety of physio-chemical techniques, including pressure, surfactant containing solutions, and solvents of varying surface tension. Superhydrophobicity is shown to be enhanced with further increases in PGC-C18 content and surface roughness (a decrease in fiber size). We demonstrate the utility of superhydrophobicity as a method for drug delivery. When the camptothecin derivatives SN-38 and CPT-11 are encapsulated within electrospun meshes, changes in air layer stability (due to changes in PGC-C18 content) dictate the rate of drug release by controlling the rate in which water can permeate into the porous 3D electrospun structure. Drug release can be tuned from 2 weeks to >10 weeks from 300 mum meshes, and meshes effectively kill a variety of cancer cell lines (lung, colon, breast) when utilized in a cytotoxicity assay. After determining that air could be used to control the rate of drug release, superhydrophobic 3D materials are explored for three applications. First, meshes are considered as a potential combination reinforcement-drug delivery device for use in resectable colorectal cancer. Second, removal of the air layer in superhydrophobic meshes is used as a method to trigger drug release. The pressure generated from high-intensity focused ultrasound (0.75-4.25 MPa) can remove the air layer spatially and temporally, allowing drug release to be controlled with application of a sufficient treatment. Third, "connective" electrosprayed coatings are deposited on chemically distinct material surfaces, which are both three-dimensional and mechanically robust. In summary, superhydrophobic 3D materials are fabricated and characterized, and are utilized as drug delivery devices. Controlled air removal from these materials offers an entirely new strategy for drug delivery, and is promising for the applications considered in this work as well as many others.

Yohe, Stefan Thomas

39

Ocular drug delivery systems: An overview  

PubMed Central

The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also, recent developments with other ocular drug delivery strategies employing in situ gels, implants, contact lens and microneedles have been discussed. PMID:25590022

Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

2014-01-01

40

Thermosensitive polymers for drug delivery  

SciTech Connect

Thermosensitive polymers (TSP) demonstrating temperature-dependent temperature-dependent swelling in water have been extensively studied in recent years. Their molecular and physical properties have been tailored for a variety of biomedical and engineering uses. This presentation will discuss TSP based on poly(N-isopropylacrylamide) and its crosslinked networks modified with hydrophobic or hydrophilic components by copolymerization blending and formation of interpenetrating polymer networks (IPNs). TSP designed for three different areas of drug delivery will be presented. First, heparin releasing temperature-sensitive polymers for the prevention of surface induced thrombosis will be presented as an example of a local macromolecular delivery from a surface of a medical device. Second, a new oral delivery device based on a novel mechanical squeezing concept, utilizing specific swelling-deswelling characteristics of temperature- and temperature/pH-sensitive hydrogels will be described. These hydrogels were synthesized to exhibit a controlled swelling-deswelling kinetics, hence a variety of release profiles may be generated: a delayed, a zero-order or an {open_quotes}on-off{close_quotes} release profile. Finally, thermally reversible polymeric gels as an extracellular matrix for the entrapment of pancreatic islet cells in biohybrid artificial pancreas for insulin delivery will be discussed.

Gutowska, A.; Kim, Sung Wan [Univ. of Utah, Salt Lake City, UT (United States)

1996-12-31

41

Nanoparticle mediated non-covalent drug delivery?  

PubMed Central

The use of nanoparticles (NPs) for enhanced drug delivery has been heavily explored during the last decade. Within the field, it is has become increasingly apparent that the physical properties of the particles themselves dictate their efficacy, and the relevant non-covalent chemistry at the NP interface also influences how drugs are immobilized and delivered. In this review, we reflect on the physical chemistry of NP mediated drug delivery (and more specifically, non-covalent drug delivery) at the three main experimental stages of drug loading, NP–drug conjugate transport, and the resulting cellular drug delivery. Through a critical evaluation of advances in drug delivery within the last decade, an outlook for biomedical applications of nanoscale transport vectors will be presented. PMID:22664231

Doane, Tennyson; Burda, Clemens

2013-01-01

42

Moving smaller in drug discovery and delivery  

Microsoft Academic Search

Advances in new micro- and nanotechnologies are accelerating the identification and evaluation of drug candidates, and the development of new delivery technologies that are required to transform biological potential into medical reality. This article will highlight the emerging micro- and nanotechnology tools, techniques and devices that are being applied to advance the fields of drug discovery and drug delivery. Many

David A. LaVan; David M. Lynn; Robert Langer

2002-01-01

43

Capillary Physiology and Drug Delivery in Central  

E-print Network

Capillary Physiology and Drug Delivery in Central Nervous System Lymphomas Peter C. Warnke, MD,1 drug delivery, we quantita- tively assessed pharmacokinetic factors in seven patients. The capillary the chemosensitivity of primary cen- tral nervous system lymphomas to water-soluble drugs could result from improved

Timmer, Jens

44

Cyclodextrins in drug delivery: An updated review  

Microsoft Academic Search

The purpose of this review is to discuss and summarize some of the interesting findings and applications of cyclodextrins\\u000a (CDs) and their derivatives in different areas of drug delivery, particularly in protein and peptide drug delivery and gene\\u000a delivery. The article highlights important CD applications in the design of various novel delivery systems like liposomes,\\u000a microspheres, microcapsules, and nanoparticles. In

Rajeswari Challa; Alka Ahuja; Javed Ali; R. K. Khar

2005-01-01

45

Novel central nervous system drug delivery systems.  

PubMed

For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases. PMID:24325540

Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

2014-05-01

46

Polymeric conjugates for drug delivery  

PubMed Central

The field of polymer therapeutics has evolved over the past decade and has resulted in the development of polymer-drug conjugates with a wide variety of architectures and chemical properties. Whereas traditional non-degradable polymeric carriers such as poly(ethylene glycol) (PEG) and N-(2-hydroxypropyl methacrylamide) (HPMA) copolymers have been translated to use in the clinic, functionalized polymer-drug conjugates are increasingly being utilized to obtain biodegradable, stimuli-sensitive, and targeted systems in an attempt to further enhance localized drug delivery and ease of elimination. In addition, the study of conjugates bearing both therapeutic and diagnostic agents has resulted in multifunctional carriers with the potential to both “see and treat” patients. In this paper, the rational design of polymer-drug conjugates will be discussed followed by a review of different classes of conjugates currently under investigation. The design and chemistry used for the synthesis of various conjugates will be presented with additional comments on their potential applications and current developmental status. PMID:22707853

Larson, Nate; Ghandehari, Hamidreza

2012-01-01

47

Drug delivery systems: An updated review  

PubMed Central

Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, cyclodextrins, among others. Nanoparticles composed of biodegradable polymers show assurance in fulfilling the stringent requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time. PMID:23071954

Tiwari, Gaurav; Tiwari, Ruchi; Sriwastawa, Birendra; Bhati, L; Pandey, S; Pandey, P; Bannerjee, Saurabh K

2012-01-01

48

Targeted Drug Delivery in Pancreatic Cancer  

PubMed Central

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 pre-clinical 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. PMID:19853645

Yu, Xianjun; Zhang, Yuqing; Chen, Changyi; Yao, Qizhi; Li, Min

2009-01-01

49

pH-responsive micelles based on (PCL)2(PDEA-b-PPEGMA)2 miktoarm polymer: controlled synthesis, characterization, and application as anticancer drug carrier  

PubMed Central

Amphiphilic A2(BC)2 miktoarm star polymers [poly(?-caprolactone)]2-[poly(2-(diethylamino)ethyl methacrylate)-b- poly(poly(ethylene glycol) methyl ether methacrylate)]2 [(PCL)2(PDEA-b-PPEGMA)2] were developed by a combination of ring opening polymerization (ROP) and continuous activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). The critical micelle concentration (CMC) values were extremely low (0.0024 to 0.0043 mg/mL), depending on the architecture of the polymers. The self-assembled empty and doxorubicin (DOX)-loaded micelles were spherical in morphologies, and the average sizes were about 63 and 110 nm. The release of DOX at pH 5.0 was much faster than that at pH 6.5 and pH 7.4. Moreover, DOX-loaded micelles could effectively inhibit the growth of cancer cells HepG2 with IC50 of 2.0 ?g/mL. Intracellular uptake demonstrated that DOX was delivered into the cells effectively after the cells were incubated with DOX-loaded micelles. Therefore, the pH-sensitive (PCL)2(PDEA-b-PPEGMA)2 micelles could be a prospective candidate as anticancer drug carrier for hydrophobic drugs with sustained release behavior. PMID:24936159

2014-01-01

50

Nanodisks: hydrophobic drug delivery vehicles.  

PubMed

Members of the class of exchangeable apolipoproteins possess the unique capacity to transform phospholipid vesicle substrates into nanoscale disk-shaped bilayers. This reaction can proceed in the presence of exogenous hydrophobic biomolecules, resulting in the formation of novel transport vehicles termed nanodisks (NDs). The objective of this study is to describe the structural organization of NDs and evaluate the utility of these complexes as hydrophobic biomolecule transport vehicles. The topics presented focus on two distinct water insoluble drugs, amphotericin B (AMB) and all trans retinoic acid (ATRA). In vitro and in vivo studies reveal that AMB-ND display potent anti-fungal and anti-protozoal activity, while ATRA-ND show promise in the treatment of cancer. The versatility conferred by the presence of a polypeptide component provides opportunities for targeted delivery of ND to cells. PMID:18318655

Ryan, Robert O

2008-03-01

51

Ocular Drug Delivery Using Ultrasound  

NASA Astrophysics Data System (ADS)

Our goal was to evaluate ultrasound (US) enhancement of drug delivery through the cornea, and the histological appearance of the cornea, up to 24 h after treatment. The aqueous humor concentration of topically applied sodium fluorescein was determined quantitatively in US-treated and sham rabbit eyes in vivo. Gross and light microscopic examinations were used to observe structural changes in the cornea 0-24 h after US exposure. The increase in the dye concentration in aqueous humor, after the simultaneous application of 880 kHz US and the dye solution (for 5 min), was 2.4 times at 0.19 W/cm2, 3.8 times at 0.34 W/cm2, and 10.6 times at 0.56 W/m2 (p<0.05). The dye delivery was found to increase with increasing US intensity, which corresponded with an increase in cavitation activity. After the separate application of US and the dye solution, the increase in the dye concentration was 3.8 times at 0.56 W/cm2 (p<0.01), while no increase was achieved at 0.19-0.34 W/cm2. The majority of damaged cells were present in the surface layer of the corneal epithelium. Corneal pits, observed in the US-treated epithelium, completely disappeared within 90 min. The application of 880 kHz ultrasound provided enhancement in the delivery of a hydrophilic compound through the cornea while producing minor changes in the corneal epithelium.

Zderic, Vesna; Clark, John I.; Vaezy, Shahram

2005-03-01

52

Nanoparticulate systems for brain delivery of drugs  

Microsoft Academic Search

The blood–brain barrier (BBB) represents an insurmountable obstacle for a large number of drugs, including antibiotics, antineoplastic agents, and a variety of central nervous system (CNS)-active drugs, especially neuropeptides. One of the possibilities to overcome this barrier is a drug delivery to the brain using nanoparticles. Drugs that have successfully been transported into the brain using this carrier include the

Jörg Kreuter

2001-01-01

53

MEMS based system for drug delivery  

Microsoft Academic Search

This paper presents the new design of transdermal drug delivery system. The system consists of integrated control electronics and microelectromechanical (MEMS) devices such as micropump, microneedles, blood pressure sensor and fluid flow sensor. Micropump and microneedles are essential components of proposed drug delivery system. Design, analysis, fabrication and characterization of piezoelectric valveless micropump and hollow out-of-plane silicon microneedles are presented

Muhammad Waseem Ashraf; Shahzadi Tayyaba; Asim Nisar; Nitin Afzulpurkar

2010-01-01

54

Dendrimers and dendritic polymers in drug delivery  

Microsoft Academic Search

The unique properties of dendrimers, such as their high degree of branching, multivalency, globular architecture and well-defined molecular weight, make them promising new scaffolds for drug delivery. In the past decade, research has increased on the design and synthesis of biocompatible dendrimers and their application to many areas of bioscience including drug delivery, immunology and the development of vaccines, antimicrobials

Elizabeth R. Gillies; Jean M. J. Fréchet

2005-01-01

55

Nanoparticles for intracellular-targeted drug delivery  

NASA Astrophysics Data System (ADS)

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.

Paulo, Cristiana S. O.; Pires das Neves, Ricardo; Ferreira, Lino S.

2011-12-01

56

Recent advances in ocular drug delivery.  

PubMed

Amongst the various routes of drug delivery, the field of ocular drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. Recent research has focused on the characteristic advantages and limitations of the various drug delivery systems, and further research will be required before the ideal system can be developed. Administration of drugs to the ocular region with conventional delivery systems leads to short contact time of the formulations on the epithelium and fast elimination of drugs. This transient residence time involves poor bioavailability of drugs which can be explained by the tear production, non-productive absorption and impermeability of corneal epithelium. Anatomy of the eye is shortly presented and is connected with ophthalmic delivery and bioavailability of drugs. In the present update on ocular dosage forms, chemical delivery systems such as prodrugs, the use of cyclodextrins to increase solubility of various drugs, the concept of penetration enhancers and other ocular drug delivery systems such as polymeric gels, bioadhesive hydrogels, in-situ forming gels with temperature-, pH-, or osmotically induced gelation, combination of polymers and colloidal systems such as liposomes, niosomes, cubosomes, microemulsions, nanoemulsions and nanoparticles are discussed. Novel ophthalmic delivery systems propose the use of many excipients to increase the viscosity or the bioadhesion of the product. New formulations like gels or colloidal systems have been tested with numerous active substances by in vitro and in vivo studies. Sustained drug release and increase in drug bioavailability have been obtained, offering the promise of innovation in drug delivery systems for ocular administration. Combining different properties of pharmaceutical formulations appears to offer a genuine synergy in bioavailability and sustained release. Promising results are obtained with colloidal systems which present very comfortable conditions of use and prolonged action. PMID:23153114

Achouri, Djamila; Alhanout, Kamel; Piccerelle, Philippe; Andrieu, Véronique

2013-11-01

57

Intravenous drug delivery in neonates: lessons learnt.  

PubMed

Intravenous drug administration presents a series of challenges that relate to the pathophysiology of the neonate and intravenous infusion systems in neonates. These challenges arise from slow intravenous flow rates, small drug volume, dead space volume and limitations on the flush volume in neonates. While there is a reasonable understanding of newborn pharmacokinetics, an appreciation of the substantial delay and variability in the rate of drug delivery from the intravenous line is often lacking. This can lead to difficulties in accurately determining the pharmacokinetic and pharmacodynamic relationship of drugs in the smallest patients. The physical variables that affect the passage of drugs through neonatal lines need to be further explored in order to improve our understanding of their impact on the delivery of drugs by this route in neonates. Through careful investigation, the underlying causes of delayed drug delivery may be identified and administration protocols can then be modified to ensure predictable, appropriate drug input kinetics. PMID:24482352

Sherwin, Catherine M T; Medlicott, Natalie J; Reith, David M; Broadbent, Roland S

2014-06-01

58

Magnetic nanoparticles for gene and drug delivery  

PubMed Central

Investigations of magnetic micro- and nanoparticles for targeted drug delivery began over 30 years ago. Since that time, major progress has been made in particle design and synthesis techniques, however, very few clinical trials have taken place. Here we review advances in magnetic nanoparticle design, in vitro and animal experiments with magnetic nanoparticle-based drug and gene delivery, and clinical trials of drug targeting. PMID:18686777

McBain, Stuart C; Yiu, Humphrey HP; Dobson, Jon

2008-01-01

59

Biologically responsive polymeric nanoparticles for drug delivery.  

PubMed

Responsive nanoparticles that release their drug cargo in accordance with a change in pH or oxidative stress are of significant clinical interest as this approach offers the opportunity to link drug delivery to a specific location or disease state. This research news article reviews the current state of this field by examining a series of published articles that highlight the novelty and benefits of using responsive polymeric particles to achieve functionally-targeted drug delivery. PMID:22988558

Colson, Yolonda L; Grinstaff, Mark W

2012-07-24

60

Nanotechnology-based drug delivery systems.  

PubMed

Nanoparticles hold tremendous potential as an effective drug delivery system. In this review we discussed recent developments in nanotechnology for drug delivery. To overcome the problems of gene and drug delivery, nanotechnology has gained interest in recent years. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. To achieve efficient drug delivery it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signalling involved in pathobiology of the disease under consideration. Several anti-cancer drugs including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been successfully formulated using nanomaterials. Quantom dots, chitosan, Polylactic/glycolic acid (PLGA) and PLGA-based nanoparticles have also been used for in vitro RNAi delivery. Brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents past the blood-brain barrier and into the brain. Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterials have been shown to cross the intact blood-brain barrier and released at therapeutic concentrations in the brain. The use of nanomaterials including peptide-based nanotubes to target the vascular endothelial growth factor (VEGF) receptor and cell adhesion molecules like integrins, cadherins and selectins, is a new approach to control disease progression. PMID:18053152

Suri, Sarabjeet Singh; Fenniri, Hicham; Singh, Baljit

2007-01-01

61

Pharmaceutical approaches to colon targeted drug delivery systems  

Microsoft Academic Search

Purpose. Although oral delivery has become a widely accepted route of administration of therapeutic drugs, the gastrointestinal tract presents several formidable barriers to drug delivery. Colonic drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon but also for its potential for the delivery of proteins

M. K. Chourasia; S. K. Jain

62

Magnetizable implants for targeted drug delivery  

NASA Astrophysics Data System (ADS)

The capability to deliver high effective dosages to specific sites in the human body has become the holy grail of drug delivery research. Drugs with proven effectiveness under in vitro investigation often reach a major roadblock under in vivo testing due to a lack of an effective delivery strategy. In addition, many clinical scenarios require delivery of agents that are therapeutic at the desired delivery point, but otherwise systemically toxic. This project proposes a method for targeted drug delivery by applying high magnetic field gradients within the body to an injected superparamagnetic colloidal fluid carrying a drug, with the aid of modest uniform magnetic field. The design involves patterning of endovascular implants, such as coronary stents, with soft magnetic coatings capable of applying high local magnetic field gradients within the body. Examination of the feasibility of the design has been focused around the treatment of coronary restenosis following angioplasty. Drug-eluting stents, which have debuted in hospitals over the past two years, have thus far reduced restenosis rates to below 10%. Our local drug delivery system is a viable alternative or enhancement to drug-eluting stents, offering increased clinician control of dose size, the ability to treat a site repeatedly, and a wide array of applications for treatment of other pathologies. The theoretical models, parallel plate and pipe flow analysis, and cell culture models presented give insight into the use of micron and sub-micron scale magnetic particles for site-specific delivery of pharmaceuticals and magnetically labeled cells.

Forbes, Zachary Graham

63

Tumor-Targeted Drug Delivery with Aptamers  

PubMed Central

Cancer is one of the leading causes of death around the world. Tumor-targeted drug delivery is one of the major areas in cancer research. Aptamers exhibit many desirable properties for tumor-targeted drug delivery, such as ease of selection and synthesis, high binding affinity and specificity, low immunogenicity, and versatile synthetic accessibility. Over the last several years, aptamers have quickly become a new class of targeting ligands for drug delivery applications. In this review, we will discuss in detail about aptamer-based delivery of chemotherapy drugs (e.g. doxorubicin, docetaxel, daunorubicin, and cisplatin), toxins (e.g. gelonin and various photodynamic therapy agents), and a variety of small interfering RNAs. Although the results are promising which warrants enthusiasm for aptamer-based drug delivery, tumor homing of aptamer-based conjugates after systemic injection has only been achieved in one report. Much remains to be done before aptamer-based drug delivery can reach clinical trials and eventually the day-to-day management of cancer patients. Therefore, future directions and challenges in aptamer-based drug delivery are also discussed. PMID:21838687

Zhang, Yin; Hong, Hao; Cai, Weibo

2011-01-01

64

Biodegradable polymeric nanoparticles as drug delivery devices  

Microsoft Academic Search

This review presents the most outstanding contributions in the field of biodegradable polymeric nanoparticles used as drug delivery systems. Methods of preparation, drug loading and drug release are covered. The most important findings on surface modification methods as well as surface characterization are covered from 1990 through mid-2000.

Kumaresh S Soppimath; Tejraj M Aminabhavi; Anandrao R Kulkarni; Walter E Rudzinski

2001-01-01

65

Transpapillary Drug Delivery to the Breast  

PubMed Central

The study was aimed at investigating localized topical drug delivery to the breast via mammary papilla (nipple). 5-fluorouracil (5-FU) and estradiol (EST) were used as model hydrophilic and hydrophobic compounds respectively. Porcine and human nipple were used for in-vitro penetration studies. The removal of keratin plug enhanced the drug transport through the nipple. The drug penetration was significantly higher through the nipple compared to breast skin. The drug’s lipophilicity had a significant influence on drug penetration through nipple. The ducts in the nipple served as a major transport pathway to the underlying breast tissue. Results showed that porcine nipple could be a potential model for human nipple. The topical application of 5-FU on the rat nipple resulted in high drug concentration in the breast and minimal drug levels in plasma and other organs. Overall, the findings from this study demonstrate the feasibility of localized drug delivery to the breast through nipple. PMID:25545150

Dave, Kaushalkumar; Averineni, Ranjith; Sahdev, Preety; Perumal, Omathanu

2014-01-01

66

Modeling oxaliplatin drug delivery to circadian rhythms in drug metabolism and host tolerance  

E-print Network

Modeling oxaliplatin drug delivery to circadian rhythms in drug metabolism and host tolerance Jean period) time-scheduled regimens for cytotoxic drug delivery by intravenous infusion, a pharmacokinetic; Pharmacokinetics-pharmacodynamics; Treatment outcome; Chronotherapy; Drug-delivery optimization Contents 1

Clairambault, Jean

67

Recent advances in ophthalmic drug delivery  

PubMed Central

Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert™ (~6 months), Retisert™ (~3 years) and Iluvien™ (~3 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems. PMID:21399724

Kompella, Uday B; Kadam, Rajendra S; Lee, Vincent HL

2011-01-01

68

Cubic phase gels as drug delivery systems.  

PubMed

Lipids have been used extensively for drug delivery in various forms such as liposomes, and solid-matrices. The focus of this review is evaluation of liquid crystalline cubic phases, spontaneously formed when amphiphilic lipids are placed in aqueous environment, for drug delivery. Cubic phases have an interesting thermodynamically stable structure consisting of curved bicontinuous lipid bilayer in three dimensions, separating two congruent networks of water channels. The unique structure of cubic phase has been extensively studied using various spectroscopic techniques and their resemblance to biomembranes has prompted many scientists to study behavior of proteins in cubic phases. The ability of cubic phase to incorporate and control release of drugs of varying size and polar characteristics, and biodegradability of lipids make it an interesting drug delivery system for various routes of administration. Cubic phases have been shown to deliver small molecule drugs and large proteins by oral and parenteral routes in addition to local delivery in vaginal and periodontal cavity. A number of different proteins in cubic phase appear to retain their native conformation and bioactivity, and are protected from chemical and physical inactivation perhaps due to the reduced activity of water and biomembrane-like structure of cubic phase. Release of drugs from cubic phase typically show diffusion controlled release from a matrix as indicated by Higuchi's square root of time release kinetics. Incorporation of drug in cubic phase can cause phase transformation to lamellar or reversed hexagonal phase depending on the polarity and concentration of the drug, which may affect the release profile. Biodegradability, phase behavior, ability to deliver drugs of varying sizes and polarity and the ability to enhance the chemical and/or physical stability of incorporated drugs and proteins make the cubic phase gel an excellent candidate for use as a drug delivery matrix. However, shorter release duration and the extremely high viscosity may limit its use to specific applications such as periodontal, mucosal, vaginal and short acting oral and parenteral drug delivery. PMID:11311994

Shah, J C; Sadhale, Y; Chilukuri, D M

2001-04-25

69

Chitosan Microspheres in Novel Drug Delivery Systems  

PubMed Central

The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems. PMID:22707817

Mitra, Analava; Dey, Baishakhi

2011-01-01

70

Fabrication of drug delivery MEMS devices  

E-print Network

There is considerable amount of interest in the immediate treatment of personnel involved in high risk situations on the battlefield. A novel approach to drug delivery on the battlefield based on MEMS technology is discussed. ...

Lei, Wang S

2007-01-01

71

Colloidal drug delivery system: amplify the ocular delivery.  

PubMed

Abstract Context: The ocular perceivers are the most voluntarily accessible organs in terms of location in the body, yet drug distribution to these tissues is one of the most intriguing and challenging endeavors and problematic to the pharmaceutical scientist. The most of ocular diseases are treated with topical application of conventional formulation, i.e. solutions, suspensions and ointment. Typically on installation of these conventional formulations, only <5% of the applied dose penetrates the cornea and reaches intraocular tissues, while a major fraction of the instilled dose is wastage due to the presence of many ocular barriers like external barriers, rapid loss of the instilled solution from the precorneal area and nasolacrimal drainage system. Systemic absorption caused systemic side effects varying from mild to life-threatening events. Objective: The main objective of this review is to explore the role of colloidal delivery of drug to minimize the drawbacks associated with them. Methods: This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of colloidal delivery systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and contact lenses containing nanoparticles have the capacity to distribute ocular drugs to categorical target sites and hold promise to revolutionize the therapy of many ocular perceiver diseases and minimized the circumscription of conventional delivery. Conclusion: Form the basis of literature review, it has been found that the novel delivery system have greater impact to maximize ocular drug absorption, and minimize systemic absorption and side effects. PMID:24892625

Ali, Javed; Fazil, Mohd; Qumbar, Mohd; Khan, Nazia; Ali, Asgar

2014-06-01

72

Drug Delivery Systems: Entering the Mainstream  

NASA Astrophysics Data System (ADS)

Drug delivery systems (DDS) such as lipid- or polymer-based nanoparticles can be designed to improve the pharmacological and therapeutic properties of drugs administered parenterally. Many of the early problems that hindered the clinical applications of particulate DDS have been overcome, with several DDS formulations of anticancer and antifungal drugs now approved for clinical use. Furthermore, there is considerable interest in exploiting the advantages of DDS for in vivo delivery of new drugs derived from proteomics or genomics research and for their use in ligand-targeted therapeutics.

Allen, Theresa M.; Cullis, Pieter R.

2004-03-01

73

Colloidal systems for CNS drug delivery  

Microsoft Academic Search

The pharmaceutical treatment of central nervous system (CNS) disorders is the second largest area of therapy, following cardiovascular diseases. Nowadays, noninvasive drug delivery systems for CNS are actively studied. The development of these new delivery systems started with the discovery that properly surface-engineered colloidal vectors, and in particular liposomes and polymeric nanoparticles, with a diameter ?200nm, were shown to be

Luca Costantino; Giovanni Tosi; Barbara Ruozi; Lucia Bondioli; Maria Angela Vandelli; Flavio Forni

2009-01-01

74

Molecular imprinted polymers as drug delivery vehicles.  

PubMed

Abstract This review is aimed to discuss the molecular imprinted polymer (MIP)-based drug delivery systems (DDS). Molecular imprinted polymers have proved to possess the potential and also as a suitable material in several areas over a long period of time. However, only recently it has been employed for pharmaceuticals and biomedical applications, particularly as drug delivery vehicles due to properties including selective recognition generated from imprinting the desired analyte, favorable in harsh experimental conditions, and feedback-controlled recognitive drug release. Hence, this review will discuss their synthesis, the reason they are selected as drug delivery vehicles and for their applications in several drug administration routes (i.e. transdermal, ocular and gastrointestinal or stimuli-reactive routes). PMID:25317753

Zaidi, Shabi Abbas

2014-10-15

75

Progress in antiretroviral drug delivery using nanotechnology  

PubMed Central

There are currently a number of antiretroviral drugs that have been approved by the Food and Drug Administration for use in the treatment of human immunodeficiency virus (HIV). More recently, antiretrovirals are being evaluated in the clinic for prevention of HIV infection. Due to the challenging nature of treatment and prevention of this disease, the use of nanocarriers to achieve more efficient delivery of antiretroviral drugs has been studied. Various forms of nanocarriers, such as nanoparticles (polymeric, inorganic, and solid lipid), liposomes, polymeric micelles, dendrimers, cyclodextrins, and cell-based nanoformulations have been studied for delivery of drugs intended for HIV prevention or therapy. The aim of this review is to provide a summary of the application of nanocarrier systems to the delivery of anti-HIV drugs, specifically antiretrovirals. For anti-HIV drugs to be effective, adequate distribution to specific sites in the body must be achieved, and effective drug concentrations must be maintained at those sites for the required period of time. Nanocarriers provide a means to overcome cellular and anatomical barriers to drug delivery. Their application in the area of HIV prevention and therapy may lead to the development of more effective drug products for combating this pandemic disease. PMID:20957115

Mallipeddi, Rama; Rohan, Lisa Cencia

2010-01-01

76

Nanotechnology in Biomaterials: Nanoparticulates as Drug Delivery Systems  

E-print Network

227 11 Nanotechnology in Biomaterials: Nanoparticulates as Drug Delivery Systems Birsen Demirbag Delivery Systems A drug delivery system (DDS) can be de ned as the system that achieves the administra the concentration, rate, time, and place of release of drugs in the body.1 The primary purpose of drug delivery

Hasýrcý, Vasýf

77

Calcium phosphate ceramics in drug delivery  

NASA Astrophysics Data System (ADS)

Calcium phosphate (CaP) particulates, cements and scaffolds have attracted significant interest as drug delivery vehicles. CaP systems, including both hydroxyapaptite and tricalcium phosphates, possess variable stoichiometry, functionality and dissolution properties which make them suitable for cellular delivery. Their chemical similarity to bone and thus biocompatibility, as well as variable surface charge density contribute to their controlled release properties. Among specific research areas, nanoparticle size, morphology, surface area due to porosity, and chemistry controlled release kinetics are the most active. This article discusses CaP systems in their particulate, cements, and scaffold forms for drug, protein, and growth factor delivery toward orthopedic and dental applications.

Bose, Susmita; Tarafder, Solaiman; Edgington, Joe; Bandyopadhyay, Amit

2011-04-01

78

Novel drug delivery systems for glaucoma  

PubMed Central

Reduction of intraocular pressure (IOP) by pharmaceutical or surgical means has long been the standard treatment for glaucoma. A number of excellent drugs are available that are effective in reducing IOP. These drugs are typically applied as eye drops. However, patient adherence can be poor, thus reducing the clinical efficacy of the drugs. Several novel delivery systems designed to address the issue of adherence and to ensure consistent reduction of IOP are currently under development. These delivery systems include contact lenses-releasing glaucoma medications, injectables such as biodegradable micro- and nanoparticles, and surgically implanted systems. These new technologies are aimed at increasing clinical efficacy by offering multiple delivery options and are capable of managing IOP for several months. There is also a desire to have complementary neuroprotective approaches for those who continue to show progression, despite IOP reduction. Many potential neuroprotective agents are not suitable for traditional oral or drop formulations. Their potential is dependent on developing suitable delivery systems that can provide the drugs in a sustained, local manner to the retina and optic nerve. Drug delivery systems have the potential to improve patient adherence, reduce side effects, increase efficacy, and ultimately, preserve sight for glaucoma patients. In this review, we discuss benefits and limitations of the current systems of delivery and application, as well as those on the horizon. PMID:21475311

Lavik, E; Kuehn, M H; Kwon, Y H

2011-01-01

79

Molecularly imprinted polymers for drug delivery  

Microsoft Academic Search

Molecular imprinting technology has an enormous potential for creating satisfactory drug dosage forms. Although its application in this field is just at an incipient stage, the use of MIPs in the design of new drug delivery systems (DDS) and devices useful in closely related fields, such as diagnostic sensors, is receiving increasing attention. Examples of MIP-based DDS can be found

Carmen Alvarez-Lorenzo; Angel Concheiro

2004-01-01

80

Section 21: Drug Discovery/Delivery Pharmacokinetic Considerations of Local Drug Delivery to the Inner Ear by  

E-print Network

1 Section 21: Drug Discovery/Delivery Pharmacokinetic Considerations of Local Drug Delivery.Plontke@uni-tuebingen.de Although there is increasing interest in the local delivery of drugs to the inner ear by applying them, consequences of changes in delivery method, applied drug concentration or even small alterations in treatment

Salt, Alec N.

81

Cyclodextrins in ophthalmic drug delivery  

Microsoft Academic Search

Most ocular diseases are treated by topical drug application in the form of aqueous eye drop solutions. Recent studies have shown that cyclodextrins are useful additives in ophthalmic formulations for increasing the aqueous solubility, aqueous stability and bioavailability of ophthalmic drugs, and to decrease drug irritation. However, these studies have also shown that there are some basic differences between ophthalmic

Thorsteinn Loftssona; Tomi Järvinen

1999-01-01

82

Polymethacrylate Microparticles Gel for Topical Drug Delivery  

Microsoft Academic Search

Purpose  Evaluating the potentials of particulate delivery systems in topical drug delivery.\\u000a \\u000a \\u000a \\u000a Methods  Polymethacrylate microparticles (MPs) incorporating verapamil hydrochloride (VRP) as a model hydrophilic drug with potential\\u000a topical clinical uses, using Eudragit RS100 and Eudragit L100 were prepared for the formulation of a composite topical gel.\\u000a The effect of initial drug loading, polymer composition, particularly the proportion of Eudragit L100 as an

Hagar Ibrahim Labouta; Labiba K. El-Khordagui

2010-01-01

83

Liposome-like Nanostructures for Drug Delivery  

PubMed Central

Liposomes are a class of well-established drug carriers that have found numerous therapeutic applications. The success of liposomes, together with recent advancements in nanotechnology, has motivated the development of various novel liposome-like nanostructures with improved drug delivery performance. These nanostructures can be categorized into five major varieties, namely: (1) polymer-stabilized liposomes, (2) nanoparticle-stabilized liposomes, (3) core-shell lipid-polymer hybrid nanoparticles, (4) natural membrane-derived vesicles, and (5) natural membrane coated nanoparticles. They have received significant attention and have become popular drug delivery platforms. Herein, we discuss the unique strengths of these liposome-like platforms in drug delivery, with a particular emphasis on how liposome-inspired novel designs have led to improved therapeutic efficacy, and review recent progress made by each platform in advancing healthcare. PMID:24392221

Gao, Weiwei; Hu, Che-Ming J.; Fang, Ronnie H.; Zhang, Liangfang

2013-01-01

84

Microfluidic device for drug delivery  

NASA Technical Reports Server (NTRS)

A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

2010-01-01

85

An implantable device for localized drug delivery and sensing  

E-print Network

There are many potential clinical applications for localized drug delivery and sensing systems, such as cancer, vaccinations, pain management, and hormone therapy. Localized drug delivery systems reduce the amount of drug ...

Daniel, Karen D

2009-01-01

86

Functional Cyclodextrin Polyrotaxanes for Drug Delivery  

NASA Astrophysics Data System (ADS)

The mobility of cyclodextrins (CDs) threaded onto a linear polymeric chain and the dethreading of the CDs from the chain are the most fascinating features seen in polyrotaxanes. These structural characteristics are very promising for their possible applications in drug delivery. Enhanced multivalent interaction between ligand-receptor systems by using ligand-conjugated polyrotaxanes would be just one of the excellent properties related to the CD mobility. Gene delivery using cytocleavable polyrotaxanes is a more practical but highly crucial issue in drug delivery. Complexation of the polyrotaxanes with DNA and its intracellular DNA release ingeniously utilizes both CD mobility and polyrotaxane dissociation to achieve effective gene delivery. Such a supramolecular approach using CD-containing polyrotaxanes is expected to exploit a new paradigm of biomaterials.

Yui, Nobuhiko; Katoono, Ryo; Yamashita, Atsushi

87

Genetically engineered nanocarriers for drug delivery  

PubMed Central

Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins. PMID:24741309

Shi, Pu; Gustafson, Joshua A; MacKay, J Andrew

2014-01-01

88

Particle Engineering Technologies for Pulmonary Drug Delivery  

Microsoft Academic Search

\\u000a Particle engineering has seen many applications in the field of ­pulmonary drug delivery due to the intimate relationship\\u000a between particle physicochemistry and aerosol product performance. In this chapter, the science behind established and emerging\\u000a particle engineering technologies is reviewed. Fundamental principles of particle engineering will be introduced. Following\\u000a a discussion of how aerosol delivery technologies integrate with particle engineering, a

Nashwa El-Gendy; Mark M. Bailey; Cory Berkland

89

Barriers to drug delivery in solid tumors  

PubMed Central

Over the last decade, significant progress has been made in the field of drug delivery. The advent of engineered nanoparticles has allowed us to circumvent the initial limitations to drug delivery such as pharmacokinetics and solubility. However, in spite of significant advances to tumor targeting, an effective treatment strategy for malignant tumors still remains elusive. Tumors possess distinct physiological features which allow them to resist traditional treatment approaches. This combined with the complexity of the biological system presents significant hurdles to the site-specific delivery of therapeutic drugs. One of the key features of engineered nanoparticles is that these can be tailored to execute specific functions. With this review, we hope to provide the reader with a clear understanding and knowledge of biological barriers and the methods to exploit these characteristics to design multifunctional nanocarriers, effect useful dosing regimens and subsequently improve therapeutic outcomes in the clinic. PMID:25068098

Sriraman, Shravan Kumar; Aryasomayajula, Bhawani; Torchilin, Vladimir P

2014-01-01

90

Drug delivery and nanoparticles: Applications and hazards  

PubMed Central

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. PMID:18686775

De Jong, Wim H; Borm, Paul JA

2008-01-01

91

Trojan Microparticles for Drug Delivery  

PubMed Central

During the last decade, the US Food and Drug Administration (FDA) have regulated a wide range of products, (foods, cosmetics, drugs, devices, veterinary, and tobacco) which may utilize micro and nanotechnology or contain nanomaterials. Nanotechnology allows scientists to create, explore, and manipulate materials in nano-regime. Such materials have chemical, physical, and biological properties that are quite different from their bulk counterparts. For pharmaceutical applications and in order to improve their administration (oral, pulmonary and dermal), the nanocarriers can be spread into microparticles. These supramolecular associations can also modulate the kinetic releases of drugs entrapped in the nanoparticles. Different strategies to produce these hybrid particles and to optimize the release kinetics of encapsulated drugs are discussed in this review. PMID:24300177

Anton, Nicolas; Jakhmola, Anshuman; Vandamme, Thierry F.

2012-01-01

92

Recent technologies in pulsatile drug delivery systems  

PubMed Central

Pulsatile drug delivery systems (PDDS) have attracted attraction because of their multiple benefits over conventional dosage forms. They deliver the drug at the right time, at the right site of action and in the right amount, which provides more benefit than conventional dosages and increased patient compliance. These systems are designed according to the circadian rhythm of the body, and the drug is released rapidly and completely as a pulse after a lag time. These products follow the sigmoid release profile characterized by a time period. These systems are beneficial for drugs with chronopharmacological behavior, where nocturnal dosing is required, and for drugs that show the first-pass effect. This review covers methods and marketed technologies that have been developed to achieve pulsatile delivery. Marketed technologies, such as PulsincapTM, Diffucaps®, CODAS®, OROS® and PULSYSTM, follow the above mechanism to render a sigmoidal drug release profile. Diseases wherein PDDS are promising include asthma, peptic ulcers, cardiovascular ailments, arthritis and attention deficit syndrome in children and hypercholesterolemia. Pulsatile drug delivery systems have the potential to bring new developments in the therapy of many diseases. PMID:23507727

Jain, Deepika; Raturi, Richa; Jain, Vikas; Bansal, Praveen; Singh, Ranjit

2011-01-01

93

Drug Delivery DOI: 10.1002/anie.201008053  

E-print Network

Drug Delivery DOI: 10.1002/anie.201008053 Self-Assembly of a Bifunctional DNA Carrier for Drug delivery carrier. This novel G-quadruplex­aptamer­ drug platform takes advantage of the target with doxorubicin[27] and photosensitizer Ce6[28] were designed to achieve selective drug delivery. Herein, we

Tan, Weihong

94

Silicon dioxide microneedles for transdermal drug delivery  

Microsoft Academic Search

In this work, the fabrication of a silicon chip for transdermal drug delivery is reported. The chip consists of: 1) an array of high-aspect ratio (up to 50), high density (1 times 106 needles\\/cm2), silicon-dioxide hollow microneedles to be inserted into the outermost part of the skin for a depth of about 100 micron (front-side); 2) some independent drug reservoirs

G. Barillaro; A. Diligenti; L. M. Strambini

2008-01-01

95

Aptamers for Targeted Drug Delivery  

PubMed Central

Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX). SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.

Ray, Partha; White, Rebekah R.

2010-01-01

96

DRUG DELIVERY INTO THE HUMAN BRAIN  

Microsoft Academic Search

Large proteins for the treatment of diseases such as Parkinson's, Alzheimer's and other disorders affecting the central nervous system (CNS) cannot easily penetrate the brain blood barrier (BBB). As an alternative to delivery through the blood stream, drugs may be inserted into the brain tissue directly using invasive release techniques. Direct injection is expected to gain importance in advanced medical

A. A. Linninger; M. B. R Somayaji; M. Xenos; S. Kondapalli

97

Targeted drug delivery via the folate receptor  

Microsoft Academic Search

The folate receptor is a highly selective tumor marker overexpressed in greater than 90% of ovarian carcinomas. Two general strategies have been developed for the targeted delivery of drugs to folate receptor-positive tumor cells: by coupling to a monoclonal antibody against the receptor and by coupling to a high affinity ligand, folic acid. First, antibodies against the folate receptor, including

Jennifer Sudimack; Robert J Lee

2000-01-01

98

Hydrolyticmicroneedles as Transdermal Drug Delivery System  

Microsoft Academic Search

We developed hydrolytic microneedles as a transdermal drug delivery system to overcome the shortcomings of existing microneedle-systems: long-term stay of broken needles in the skin and high cost for safe disposal of used needles. The present microneedles spontaneously dissolve by hydrolysis in human skin as well as in the (boiled) water. We verified their basic utility through experiments.

T. Miyano; T. Miyachi; T. Okanishi; H. Todo; K. Sugibayashi; T. Uemura; N. Takano; S. Konishi

2007-01-01

99

Strategies for antimicrobial drug delivery to biofilm.  

PubMed

Biofilms are formed by the attachment of single or mixed microbial communities to a variety of biological and/or synthetic surfaces. Biofilm micro-organisms benefit from many advantages of the polymicrobial environment including increased resistance against antimicrobials and protection against the host organism's defence mechanisms. These benefits stem from a number of structural and physiological differences between planktonic and biofilm-resident microbes, but two main factors are the presence of extracellular polymeric substances (EPS) and quorum sensing communication. Once formed, biofilms begin to synthesise EPS, a complex viscous matrix composed of a variety of macromolecules including proteins, lipids and polysaccharides. In terms of drug delivery strategies, it is the EPS that presents the greatest barrier to diffusion for drug delivery systems and free antimicrobial agents alike. In addition to EPS synthesis, biofilm-based micro-organisms can also produce small, diffusible signalling molecules involved in cell density-dependent intercellular communication, or quorum sensing. Not only does quorum sensing allow microbes to detect critical cell density numbers, but it also permits co-ordinated behaviour within the biofilm, such as iron chelation and defensive antibiotic activities. Against this backdrop of microbial defence and cell density-specific communication, a variety of drug delivery systems have been developed to deliver antimicrobial agents and antibiotics to extracellular and/or intracellular targets, or more recently, to interfere with the specific mechanisms of quorum sensing. Successful delivery strategies have employed lipidic and polymeric-based formulations such as liposomes and cyclodextrins respectively, in addition to inorganic carriers e.g. metal nanoparticles. This review will examine a range of drug delivery systems and their application to biofilm delivery, as well as pharmaceutical formulations with innate antimicrobial properties such as silver nanoparticles and microemulsions. PMID:25189862

Martin, Claire; Low, Wan Li; Gupta, Abhishek; Amin, Mohd Cairul Iqbal Mohd; Radecka, Iza; Britland, Stephen T; Raj, Prem; Kenward, Ken M A

2015-01-01

100

Drug delivery to brain tumors  

Microsoft Academic Search

A prerequisite for the efficacy of any cancer drug is that it reaches the tumor in therapeutic concentrations. This is difficult\\u000a to accomplish in most systemic solid tumors because of factors such as variable hypoxia, intratumoral pressure gradients,\\u000a and abnormal vasculature within the tumors. In brain cancer, the situation is complicated by the blood-brain barrier (BBB)\\u000a and blood-cerebrospinal fluid barrier,

Jaishri Blakeley

2008-01-01

101

Mucoadhesive drug delivery system: An overview  

PubMed Central

Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules and increase the residence time of the dosage form at the site of absorption. The drugs which have local action or those which have maximum absorption in gastrointestinal tract (GIT) require increased duration of stay in GIT. Thus, mucoadhesive dosage forms are advantageous in increasing the drug plasma concentrations and also therapeutic activity. In this regard, this review covers the areas of mechanisms and theories of mucoadhesion, factors influencing the mucoadhesive devices and also various mucoadhesive dosage forms. PMID:22247877

Boddupalli, Bindu M.; Mohammed, Zulkar N. K.; Nath, Ravinder A.; Banji, David

2010-01-01

102

Structural DNA nanotechnology for intelligent drug delivery.  

PubMed

Drug delivery carriers have been popularly employed to improve solubility, stability, and efficacy of chemical and biomolecular drugs. Despite the rapid progress in this field, it remains a great challenge to develop an ideal carrier with minimal cytotoxicity, high biocompatibility and intelligence for targeted controlled release. The emergence of DNA nanotechnology offers unprecedented opportunities in this regard. Due to the unparalleled self-recognition properties of DNA molecules, it is possible to create numerous artificial DNA nanostructures with well-defined structures and DNA nanodevices with precisely controlled motions. More importantly, recent studies have proven that DNA nanostructures possess greater permeability to the membrane barrier of cells, which pave the way to developing new drug delivery carriers with nucleic acids, are summarized. In this Concept, recent advances on the design and fabrication of both static and dynamic DNA nanostructures, and the use of these nanostructures for the delivery of various types of drugs, are highlighted. It is also demonstrated that dynamic DNA nanostructures provide the required intelligence to realize logically controlled drug release. PMID:24955859

Chao, Jie; Liu, Huajie; Su, Shao; Wang, Lianhui; Huang, Wei; Fan, Chunhai

2014-11-01

103

Microneedle delivery for improved efficacy of antiretroviral and antibiotic drugs  

E-print Network

Two classes of drugs, antiretrovirals and antibiotics, could benefit greatly from delivery through microneedles. Microneedles (MN) offer an increase in efficacy for these drugs by providing delivery to the lymphatic system ...

Stauber, Zachary Jason

2012-01-01

104

A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery  

PubMed Central

Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (IN) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+IN) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (IV) drug injection is employed, FUS was also applied after IV injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within the targeted region compared with that achieved by IN only. Despite the fact that the IN route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+IN was not significantly different from that of FUS+IV. As a new drug delivery platform, the FUS+IN technique is potentially useful for treating CNS diseases. PMID:25279463

Chen, Hong; Chen, Cherry C.; Acosta, Camilo; Wu, Shih-Ying; Sun, Tao; Konofagou, Elisa E.

2014-01-01

105

Intracarotid Delivery of Drugs: The Potential and the Pitfalls  

PubMed Central

The major efforts to selectively deliver drugs to the brain in the last decade have relied on smart molecular techniques to penetrate the blood brain barrier while intraarterial drug delivery has drawn relatively little attention. In the last decade there have been rapid advances in endovascular techniques. Modern endovascular procedures can permit highly targeted drug delivery by intracarotid route. Intracarotid drug delivery can be the primary route of drug delivery or it could be used to facilitate the delivery of smart-neuropharmaceuticals. There have been few attempts to systematically understand the kinetics of intracarotid drugs. Anecdotal data suggests that intracarotid drug delivery is effective in the treatment of cerebral vasospasm, thromboembolic strokes, and neoplasms. Neuroanesthesiologists are frequently involved in the care of such high-risk patients. Therefore, it is necessary to understand the applications of intracarotid drug delivery and the unusual kinetics of intracarotid drugs. PMID:18719453

Joshi, Shailendra; Meyers, Phillip M.; Ornstein, Eugene

2014-01-01

106

BASIC INVESTIGATIONS Ultrasound-Enhanced Transcorneal Drug Delivery  

E-print Network

BASIC INVESTIGATIONS Ultrasound-Enhanced Transcorneal Drug Delivery Vesna Zderic, PhD,* John I. Here, we report on our investigation of the mecha- nisms of ultrasound-enhanced drug delivery through of drug delivery through the cornea appears to result from minor structural alterations in the epi

Clark, John

107

REVIEW Open Access Bioresponsive matrices in drug delivery  

E-print Network

REVIEW Open Access Bioresponsive matrices in drug delivery Jin-Oh You, Dariela Almeda, George JC Ye, Debra T Auguste* Abstract For years, the field of drug delivery has focused on (1) controlling, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehi

Auguste, Debra T.

108

Trojan particles: Large porous carriers of nanoparticles for drug delivery  

E-print Network

Trojan particles: Large porous carriers of nanoparticles for drug delivery N. Tsapis*, D. Bennett the drug release and delivery potential of nanoparticle (NP) systems with the ease of flow, processing drug delivery (12, 13). As a result of these limitations, NPs are not presently being explored

109

Electrically-assisted transdermal drug delivery.  

PubMed

Electrically-assisted transdermal delivery (EATDD) is the facilitated transport of compounds across the skin using an electromotive force. It has been extensively explored as a potential means for delivering peptides and other hydrophilic, acid-labile or orally unstable products of biotechnology. The predominant mechanism for delivery is iontophoresis, although electroosmosis and electroporation have also been investigated. The focus of this review is to put these different mechanisms in perspective and relate them to the drug and skin model system being investigated. PMID:9210183

Riviere, J E; Heit, M C

1997-06-01

110

ATP-triggered anticancer drug delivery  

NASA Astrophysics Data System (ADS)

Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24??M in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.

Mo, Ran; Jiang, Tianyue; Disanto, Rocco; Tai, Wanyi; Gu, Zhen

2014-03-01

111

Drug Delivery Nanoparticles in Skin Cancers  

PubMed Central

Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported. PMID:25101298

Dianzani, Chiara; Zara, Gian Paolo; Maina, Giovanni; Pettazzoni, Piergiorgio; Pizzimenti, Stefania; Rossi, Federica; Gigliotti, Casimiro Luca; Ciamporcero, Eric Stefano; Daga, Martina; Barrera, Giuseppina

2014-01-01

112

BioMEMS in drug delivery.  

PubMed

The drive to design micro-scale medical devices which can be reliably and uniformly mass produced has prompted many researchers to adapt processing technologies from the semiconductor industry. By operating at a much smaller length scale, the resulting biologically-oriented microelectromechanical systems (BioMEMS) provide many opportunities for improved drug delivery: Low-dose vaccinations and painless transdermal drug delivery are possible through precisely engineered microneedles which pierce the skin's barrier layer without reaching the nerves. Low-power, low-volume BioMEMS pumps and reservoirs can be implanted where conventional pumping systems cannot. Drug formulations with geometrically complex, extremely uniform micro- and nano-particles are formed through micromolding or with microfluidic devices. This review describes these BioMEMS technologies and discusses their current state of implementation. As these technologies continue to develop and capitalize on their simpler integration with other MEMS-based systems such as computer controls and telemetry, BioMEMS' impact on the field of drug delivery will continue to increase. PMID:23856413

Nuxoll, Eric

2013-11-01

113

Protein-Based Nanomedicine Platforms for Drug Delivery  

SciTech Connect

Drug delivery systems have been developed for many years, however some limitations still hurdle the pace of going to clinical phase, for example, poor biodistribution, drug molecule cytotoxicity, tissue damage, quick clearance from the circulation system, solubility and stability of drug molecules. To overcome the limitations of drug delivery, biomaterials have to be developed and applied to drug delivery to protect the drug molecules and to enhance the drug’s efficacy. Protein-based nanomedicine platforms for drug delivery are platforms comprised of naturally self-assembled protein subunits of the same protein or a combination of proteins making up a complete system. They are ideal for drug delivery platforms due to their biocompatibility and biodegradability coupled with low toxicity. A variety of proteins have been used and characterized for drug delivery systems including the ferritin/apoferritin protein cage, plant derived viral capsids, the small Heat shock protein (sHsp) cage, albumin, soy and whey protein, collagen, and gelatin. There are many different types and shapes that have been prepared to deliver drug molecules using protein-based platforms including the various protein cages, microspheres, nanoparticles, hydrogels, films, minirods and minipellets. There are over 30 therapeutic compounds that have been investigated with protein-based drug delivery platforms for the potential treatment of various cancers, infectious diseases, chronic diseases, autoimmune diseases. In protein-based drug delivery platforms, protein cage is the most newly developed biomaterials for drug delivery and therapeutic applications. Their uniform sizes, multifunctions, and biodegradability push them to the frontier for drug delivery. In this review, the recent strategic development of drug delivery has been discussed with a special emphasis upon the polymer based, especially protein-based nanomedicine platforms for drug delivery. The advantages and disadvantages are also discussed for each type of protein based drug delivery system.

Ma Ham, Aihui; Tang, Zhiwen; Wu, Hong; Wang, Jun; Lin, Yuehe

2009-08-03

114

Nanotechnology Approaches for Ocular Drug Delivery  

PubMed Central

Blindness is a major health concern worldwide that has a powerful impact on afflicted individuals and their families, and is associated with enormous socio-economical consequences. The Middle East is heavily impacted by blindness, and the problem there is augmented by an increasing incidence of diabetes in the population. An appropriate drug/gene delivery system that can sustain and deliver therapeutics to the target tissues and cells is a key need for ocular therapies. The application of nanotechnology in medicine is undergoing rapid progress, and the recent developments in nanomedicine-based therapeutic approaches may bring significant benefits to address the leading causes of blindness associated with cataract, glaucoma, diabetic retinopathy and retinal degeneration. In this brief review, we highlight some promising nanomedicine-based therapeutic approaches for drug and gene delivery to the anterior and posterior segments. PMID:23580849

Xu, Qingguo; Kambhampati, Siva P.; Kannan, Rangaramanujam M.

2013-01-01

115

Nanotechnology approaches for ocular drug delivery.  

PubMed

Blindness is a major health concern worldwide that has a powerful impact on afflicted individuals and their families, and is associated with enormous socio-economical consequences. The Middle East is heavily impacted by blindness, and the problem there is augmented by an increasing incidence of diabetes in the population. An appropriate drug/gene delivery system that can sustain and deliver therapeutics to the target tissues and cells is a key need for ocular therapies. The application of nanotechnology in medicine is undergoing rapid progress, and the recent developments in nanomedicine-based therapeutic approaches may bring significant benefits to address the leading causes of blindness associated with cataract, glaucoma, diabetic retinopathy and retinal degeneration. In this brief review, we highlight some promising nanomedicine-based therapeutic approaches for drug and gene delivery to the anterior and posterior segments. PMID:23580849

Xu, Qingguo; Kambhampati, Siva P; Kannan, Rangaramanujam M

2013-01-01

116

Caged protein nanoparticles for drug delivery.  

PubMed

Caged protein nanoparticles possess many desirable features for drug delivery, such as ideal sizes for endocytosis, non-toxic biodegradability, and the ability to functionalize at three distinct interfaces (external, internal, and inter-subunit) using the tools of protein engineering. Researchers have harnessed these attributes by covalently and non-covalently loading therapeutic molecules through mechanisms that facilitate release within specific microenvironments. Effective delivery depends on several factors, including specific targeting, cell uptake, release kinetics, and systemic clearance. The innate ability of the immune system to recognize and respond to proteins has recently been exploited to deliver therapeutic compounds with these platforms for immunomodulation. The diversity of drugs, loading/release mechanisms, therapeutic targets, and therapeutic efficacy are discussed in this review. PMID:24832078

Molino, Nicholas M; Wang, Szu-Wen

2014-08-01

117

Polysaccharide-Based Micelles for Drug Delivery  

PubMed Central

Delivery of hydrophobic molecules and proteins has been an issue due to poor bioavailability following administration. Thus, micelle carrier systems are being investigated to improve drug solubility and stability. Due to problems with toxicity and immunogenicity, natural polysaccharides are being explored as substitutes for synthetic polymers in the development of new micelle systems. By grafting hydrophobic moieties to the polysaccharide backbone, self-assembled micelles can be readily formed in aqueous solution. Many polysaccharides also possess inherent bioactivity that can facilitate mucoadhesion, enhanced targeting of specific tissues, and a reduction in the inflammatory response. Furthermore, the hydrophilic nature of some polysaccharides can be exploited to enhance circulatory stability. This review will highlight the advantages of polysaccharide use in the development of drug delivery systems and will provide an overview of the polysaccharide-based micelles that have been developed to date. PMID:24300453

Zhang, Nan; Wardwell, Patricia R.; Bader, Rebecca A.

2013-01-01

118

Microfluidics of nano-drug delivery  

Microsoft Academic Search

After a brief review of microfluidics, a bio-MEMS application in terms of nanofluid flow in microchannels is presented. Specifically, the transient 3-D problem of controlled nano-drug delivery in a heated microchannel has been numerically solved to gain new physical insight and to determine suitable geometric and operational system parameters. Computer model accuracy was verified via numerical tests and comparisons with

Clement Kleinstreuer; Jie Li; Junemo Koo

2008-01-01

119

Environment-sensitive hydrogels for drug delivery  

Microsoft Academic Search

Environmentally sensitive hydrogels have enormous potential in various applications. Some environmental variables, such as low pH and elevated temperatures, are found in the body. For this reason, either pH-sensitive and\\/or temperature-sensitive hydrogels can be used for site-specific controlled drug delivery. Hydrogels that are responsive to specific molecules, such as glucose or antigens, can be used as biosensors as well as

Yong Qiu

2001-01-01

120

MICROFABRICATED MICRONEEDLES FOR GENE AND DRUG DELIVERY  

Microsoft Academic Search

? Abstract By incorporating techniques adapted from the microelectronics,indus- try, the field of microfabrication has allowed the creation of microneedles, which have the potential to improve,existing biological-laboratory and medical,devices and to en- able novel devices for gene and drug delivery. Dense arrays of microneedles,have been used to deliver DNA into cells. Many cells are treated at once, which is much

Devin V. McAllister; Mark G. Allen; Mark R. Prausnitz

2000-01-01

121

Approaches for drug delivery with intracortical probes.  

PubMed

Intracortical microprobes allow the precise monitoring of electrical and chemical signaling and are widely used in neuroscience. Microelectromechanical system (MEMS) technologies have greatly enhanced the integration of multifunctional probes by facilitating the combination of multiple recording electrodes and drug delivery channels in a single probe. Depending on the neuroscientific application, various assembly strategies are required in addition to the microprobe fabrication itself. This paper summarizes recent advances in the fabrication and assembly of micromachined silicon probes for drug delivery achieved within the EU-funded research project NeuroProbes. The described fabrication process combines a two-wafer silicon bonding process with deep reactive ion etching, wafer grinding, and thin film patterning and offers a maximum in design flexibility. By applying this process, three general comb-like microprobe designs featuring up to four 8-mm-long shafts, cross sections from 150×200 to 250×250 µm², and different electrode and fluidic channel configurations are realized. Furthermore, we discuss the development and application of different probe assemblies for acute, semichronic, and chronic applications, including comb and array assemblies, floating microprobe arrays, as well as the complete drug delivery system NeuroMedicator for small animal research. PMID:24101367

Spieth, Sven; Schumacher, Axel; Trenkle, Fabian; Brett, Olivia; Seidl, Karsten; Herwik, Stanislav; Kisban, Sebastian; Ruther, Patrick; Paul, Oliver; Aarts, Arno A A; Neves, Hercules P; Rich, P Dylan; Theobald, David E; Holtzman, Tahl; Dalley, Jeffrey W; Verhoef, Bram-Ernst; Janssen, Peter; Zengerle, Roland

2014-08-01

122

A model of axonal transport drug delivery  

NASA Astrophysics Data System (ADS)

In this paper a model of targeted drug delivery by means of active (motor-driven) axonal transport is developed. The model is motivated by recent experimental research by Filler et al. (A.G. Filler, G.T. Whiteside, M. Bacon, M. Frederickson, F.A. Howe, M.D. Rabinowitz, A.J. Sokoloff, T.W. Deacon, C. Abell, R. Munglani, J.R. Griffiths, B.A. Bell, A.M.L. Lever, Tri-partite complex for axonal transport drug delivery achieves pharmacological effect, Bmc Neuroscience 11 (2010) 8) that reported synthesis and pharmacological efficiency tests of a tri-partite complex designed for axonal transport drug delivery. The developed model accounts for two populations of pharmaceutical agent complexes (PACs): PACs that are transported retrogradely by dynein motors and PACs that are accumulated in the axon at the Nodes of Ranvier. The transitions between these two populations of PACs are described by first-order reactions. An analytical solution of the coupled system of transient equations describing conservations of these two populations of PACs is obtained by using Laplace transform. Numerical results for various combinations of parameter values are presented and their physical significance is discussed.

Kuznetsov, Andrey V.

2012-04-01

123

Protein and Peptide Drug Delivery: Oral Approaches  

PubMed Central

Till recent, injections remained the most common means for administering therapeutic proteins and peptides because of their poor oral bioavailability. However, oral route would be preferred to any other route because of its high levels of patient acceptance and long term compliance, which increases the therapeutic value of the drug. Designing and formulating a polypeptide drug delivery through the gastro intestinal tract has been a persistent challenge because of their unfavorable physicochemical properties, which includes enzymatic degradation, poor membrane permeability and large molecular size. The main challenge is to improve the oral bioavailability from less than 1% to at least 30-50%. Consequently, efforts have intensified over the past few decades, where every oral dosage form used for the conventional small molecule drugs has been used to explore oral protein and peptide delivery. Various strategies currently under investigation include chemical modification, formulation vehicles and use of enzyme inhibitors, absorption enhancers and mucoadhesive polymers. This review summarizes different pharmaceutical approaches which overcome various physiological barriers that help to improve oral bioavailability that ultimately achieve formulation goals for oral delivery. PMID:20046732

Shaji, Jessy; Patole, V.

2008-01-01

124

Nano and Microparticles as Controlled Drug Delivery Devices  

Microsoft Academic Search

Although, the drug delivery system (DDS) concept is not new, great progress has recently been made in the treatment of a variety of diseases. Targeting delivery of drugs to the diseased lesions is one of the most important aspects of DDS. To convey a sufficient dose of drug to the lesion, suitable carriers of drugs are needed. Nano and microparticle

Majeti N. V. Ravi

2000-01-01

125

Polymer Implants for Intratumoral Drug Delivery and Cancer Therapy  

E-print Network

Polymer Implants for Intratumoral Drug Delivery and Cancer Therapy BRENT D. WEINBERG,1 ELVIN BLANCO optimal drug release kinetics to improve drug delivery efficiency and antitumor efficacy when treating unresectable tumors. Modeling of drug transport properties in different tissue environments has provided

Gao, Jinming

126

Drug Delivery to the Ischemic Brain  

PubMed Central

Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

Thompson, Brandon J.; Ronaldson, Patrick T.

2014-01-01

127

Controlling drug delivery across the placenta: A commentary  

E-print Network

A challenge in modern drug therapy is to develop strategies for safer and more selective targeting of drug delivery in pregnancy. Specifically, approaches are needed that would restrict unnecessary drug exposure to either ...

Audus, Kenneth L.

1999-01-01

128

Stimuli-responsive nanocarriers for drug delivery  

NASA Astrophysics Data System (ADS)

Spurred by recent progress in materials chemistry and drug delivery, stimuli-responsive devices that deliver a drug in spatial-, temporal- and dosage-controlled fashions have become possible. Implementation of such devices requires the use of biocompatible materials that are susceptible to a specific physical incitement or that, in response to a specific stimulus, undergo a protonation, a hydrolytic cleavage or a (supra)molecular conformational change. In this Review, we discuss recent advances in the design of nanoscale stimuli-responsive systems that are able to control drug biodistribution in response to specific stimuli, either exogenous (variations in temperature, magnetic field, ultrasound intensity, light or electric pulses) or endogenous (changes in pH, enzyme concentration or redox gradients).

Mura, Simona; Nicolas, Julien; Couvreur, Patrick

2013-11-01

129

Recent advances in nanotechnology based drug delivery to the brain  

PubMed Central

Drug delivery into the brain was difficult due to the existence of blood brain barrier, which only permits some molecules to pass through freely. In past decades, nanotechnology has enabled many technical advances including drug delivery into the brain with high efficiency and accuracy. In the present paper, we summarize recent important advances in employing nanotechnology for drug delivery to the brain as well as controlled drug release. PMID:20700653

Lin, Li-Na; Song, Lei; Liu, Fang-Fang; Sha, Jin-Xiu

2010-01-01

130

Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery  

PubMed Central

Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments. PMID:22312236

Moodley, Kovanya; Pillay, Viness; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Kumar, Pradeep; Cooppan, Shivaan; Bawa, Priya

2012-01-01

131

Drug accumulation by means of noninvasive magnetic drug delivery system  

NASA Astrophysics Data System (ADS)

The medication is one of the most general treatment methods, but drugs diffuse in the normal tissues other than the target part by the blood circulation. Therefore, side effect in the medication, particularly for a drug with strong effect such as anti-cancer drug, are a serious issue. Drug Delivery System (DDS) which accumulates the drug locally in the human body is one of the techniques to solve the side-effects. Magnetic Drug Delivery System (MDDS) is one of the active DDSs, which uses the magnetic force. The objective of this study is to accumulate the ferromagnetic drugs noninvasively in the deep part of the body by using MDDS. It is necessary to generate high magnetic field and magnetic gradient at the target part to reduce the side-effects to the tissues with no diseases. The biomimetic model was composed, which consists of multiple model organs connected with diverged blood vessel model. The arrangement of magnetic field was examined to accumulate ferromagnetic drug particles in the target model organ by using a superconducting bulk magnet which can generate high magnetic fields. The arrangement of magnet was designed to generate high and stable magnetic field at the target model organ. The accumulation experiment of ferromagnetic particles has been conducted. In this study, rotating HTS bulk magnet around the axis of blood vessels by centering on the target part was suggested, and the model experiment for magnet rotation was conducted. As a result, the accumulation of the ferromagnetic particles to the target model organ in the deep part was confirmed.

Chuzawa, M.; Mishima, F.; Akiyama, Y.; Nishijima, S.

2011-11-01

132

Ultrasound triggered, image guided, local drug delivery.  

PubMed

Ultrasound allows the deposition of thermal and mechanical energies deep inside the human body in a non-invasive way. Ultrasound can be focused within a region with a diameter of about 1mm. The bio-effects of ultrasound can lead to local tissue heating, cavitation, and radiation force, which can be used for 1) local drug release from nanocarriers circulating in the blood, 2) increased extravasation of drugs and/or carriers, and 3) enhanced diffusivity of drugs. When using nanocarriers sensitive to mechanical forces (the oscillating ultrasound pressure waves) and/or sensitive to temperature, the content of the nanocarriers can be released locally. Thermo-sensitive liposomes have been suggested for local drug release in combination with local hyperthermia more than 25 years ago. Microbubbles may be designed specifically to enhance cavitation effects. Real-time imaging methods, such as magnetic resonance, optical and ultrasound imaging have led to novel insights and methods for ultrasound triggered drug delivery. Image guidance of ultrasound can be used for: 1) target identification and characterization; 2) spatio-temporal guidance of actions to release or activate the drugs and/or permeabilize membranes; 3) evaluation of bio-distribution, pharmacokinetics and pharmacodynamics; and 4) physiological read-outs to evaluate the therapeutic efficacy. PMID:20709123

Deckers, Roel; Moonen, Chrit T W

2010-11-20

133

Topical Drug Delivery for Chronic Rhinosinusitis  

PubMed Central

Chronic rhinosinusitis is a multifactorial disorder that may be heterogeneous in presentation and clinical course. While the introduction of endoscopic sinus surgery revolutionized surgical management and has led to significantly improved patient outcomes, medical therapy remains the foundation of long-term care of chronic rhinosinusitis, particularly in surgically recalcitrant cases. A variety of devices and pharmaceutical agents have been developed to apply topical medical therapy to the sinuses, taking advantage of the access provided by endoscopic surgery. The goal of topical therapy is to address the inflammation, infection, and mucociliary dysfunction that underlies the disease. Major factors that impact success include the patient’s sinus anatomy and the dynamics of the delivery device. Despite a growing number of topical treatment options, the evidence-based literature to support their use is limited. In this article, we comprehensively review current delivery methods and the available topical agents. We also discuss biotechnological advances that promise enhanced delivery in the future, and evolving pharmacotherapeutical compounds that may be added to rhinologist’s armamentarium. A complete understand of topical drug delivery is increasingly essential to the management of chronic rhinosinusitis when traditional forms of medical therapy and surgery have failed. PMID:23525506

Liang, Jonathan; Lane, Andrew P.

2013-01-01

134

Polymeric micelles for multi-drug delivery in cancer.  

PubMed

Drug combinations are common in cancer treatment and are rapidly evolving, moving beyond chemotherapy combinations to combinations of signal transduction inhibitors. For the delivery of drug combinations, i.e., multi-drug delivery, major considerations are synergy, dose regimen (concurrent versus sequential), pharmacokinetics, toxicity, and safety. In this contribution, we review recent research on polymeric micelles for multi-drug delivery in cancer. In concurrent drug delivery, polymeric micelles deliver multi-poorly water-soluble anticancer agents, satisfying strict requirements in solubility, stability, and safety. In sequential drug delivery, polymeric micelles participate in pretreatment strategies that "prime" solid tumors and enhance the penetration of secondarily administered anticancer agent or nanocarrier. The improved delivery of multiple poorly water-soluble anticancer agents by polymeric micelles via concurrent or sequential regimens offers novel and interesting strategies for drug combinations in cancer treatment. PMID:25501872

Cho, Hyunah; Lai, Tsz Chung; Tomoda, Keishiro; Kwon, Glen S

2015-02-01

135

In Situ Forming Polymeric Drug Delivery Systems  

PubMed Central

In situ forming polymeric formulations are drug delivery systems that are in sol form before administration in the body, but once administered, undergo gelation in situ, to form a gel. The formation of gels depends on factors like temperature modulation, pH change, presence of ions and ultra violet irradiation, from which the drug gets released in a sustained and controlled manner. Various polymers that are used for the formulation of in situ gels include gellan gum, alginic acid, xyloglucan, pectin, chitosan, poly(DL-lactic acid), poly(DL-lactide-co-glycolide) and poly-caprolactone. The choice of solvents like water, dimethylsulphoxide, N-methyl pyrrolidone, triacetin and 2-pyrrolidone for these formulations depends on the solubility of polymer used. Mainly in situ gels are administered by oral, ocular, rectal, vaginal, injectable and intraperitoneal routes. The in situ gel forming polymeric formulations offer several advantages like sustained and prolonged action in comparison to conventional drug delivery systems. The article presents a detailed review of these types of polymeric systems, their evaluation, advancements and their commercial formulations. From a manufacturing point of view, the production of such devices is less complex and thus lowers the investment and manufacturing cost. PMID:20490289

Madan, M.; Bajaj, A.; Lewis, S.; Udupa, N.; Baig, J. A.

2009-01-01

136

Adenovirus Dodecahedron, as a Drug Delivery Vector  

PubMed Central

Background Bleomycin (BLM) is an anticancer antibiotic used in many cancer regimens. Its utility is limited by systemic toxicity and dose-dependent pneumonitis able to progress to lung fibrosis. The latter can affect up to nearly 50% of the total patient population, out of which 3% will die. We propose to improve BLM delivery by tethering it to an efficient delivery vector. Adenovirus (Ad) dodecahedron base (DB) is a particulate vector composed of 12 copies of a pentameric viral protein responsible for virus penetration. The vector efficiently penetrates the plasma membrane, is liberated in the cytoplasm and has a propensity to concentrate around the nucleus; up to 300000 particles can be observed in one cell in vitro. Principal Findings Dodecahedron (Dd) structure is preserved at up to about 50°C at pH 7–8 and during dialysis, freezing and drying in the speed-vac in the presence of 150 mM ammonium sulfate, as well as during lyophilization in the presence of cryoprotectants. The vector is also stable in human serum for 2 h at 37°C. We prepared a Dd-BLM conjugate which upon penetration induced death of transformed cells. Similarly to free bleomycin, Dd-BLM caused dsDNA breaks. Significantly, effective cytotoxic concentration of BLM delivered with Dd was 100 times lower than that of free bleomycin. Conclusions/Significance Stability studies show that Dds can be conveniently stored and transported, and can potentially be used for therapeutic purposes under various climates. Successful BLM delivery by Ad Dds demonstrates that the use of virus like particle (VLP) results in significantly improved drug bioavailability. These experiments open new vistas for delivery of non-permeant labile drugs. PMID:19440379

Zochowska, Monika; Paca, Agnieszka; Schoehn, Guy; Andrieu, Jean-Pierre; Chroboczek, Jadwiga; Dublet, Bernard; Szolajska, Ewa

2009-01-01

137

Poloxamine-based nanomaterials for drug delivery.  

PubMed

Poloxamines (Tetronic) are X-shaped amphiphilic block copolymers formed by four arms of poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) blocks bonded to a central ethylenediamine moiety. Such a structure confers multi-responsive behaviour, namely temperature and pH-sensitiveness. At relatively low concentrations but above the critical micellar concentration (CMC), poloxamines generate polymeric micelles. Due to the presence of a hydrophobic core, these nanocarriers are useful in the solubilization and stabilization of poorly water-soluble drugs. Moreover, chemical modification of the micellar core is feasible. These remarkable and unique features, compared to the well-known linear poloxamers, have motivated an increasing interest in the study and application of the branched derivatives in different emerging disciplines. The present review concisely overviews the most important developments comprising the application of poloxamines in drug delivery, mainly as micellar carriers capable of enhancing drug solubility and stability, and also as surface modifiers in the technology of stealth polymeric nanoparticles. Their potential for the administration of drugs by different routes and the improvement of the drug bioavailability and therapeutic effect are discussed. PMID:20036890

Alvarez-Lorenzo, Carmen; Rey-Rico, Ana; Sosnik, Alejandro; Taboada, Pablo; Concheiro, Angel

2010-01-01

138

Biomedical Imaging in Implantable Drug Delivery Systems.  

PubMed

Implantable drug delivery systems (DDS) provide a platform for sustained release of therapeutic agents over a period of weeks to months and sometimes years. Such strategies are typically used clinically to increase patient compliance by replacing frequent administration of drugs such as contraceptives and hormones to maintain plasma concentration within the therapeutic window. Implantable or injectable systems have also been investigated as a means of local drug administration which favors high drug concentration at a site of interest, such as a tumor, while reducing systemic drug exposure to minimize unwanted side effects. Significant advances in the field of local DDS have led to increasingly sophisticated technology with new challenges including quantification of local and systemic pharmacokinetics and implant-body interactions. Because many of these sought-after parameters are highly dependent on the tissue properties at the implantation site, and rarely represented adequately with in vitro models, new nondestructive techniques that can be used to study implants in situ are highly desirable. Versatile imaging tools can meet this need and provide quantitative data on morphological and functional aspects of implantable systems. The focus of this review article is an overview of current biomedical imaging techniques, including magnetic resonance imaging (MRI), ultrasound imaging, optical imaging, X-ray and computed tomography (CT), and their application in evaluation of implantable DDS. PMID:25418857

Zhou, Haoyan; Hernandez, Christopher; Goss, Monika; Gawlik, Anna; Exner, Agata A

2014-11-22

139

Non-viral drug delivery systems for immune modulation  

E-print Network

Biodegradable polymer particles have diverse applications in drug delivery. The main objective of this thesis was to apply these delivery systems to modulating the immune system. We optimized particle formulations for the ...

Fuller, Jason E., Ph. D. Massachusetts Institute of Technology

2008-01-01

140

Pulmonary drug delivery by powder aerosols.  

PubMed

The efficacy of pharmaceutical aerosols relates to its deposition in the clinically relevant regions of the lungs, which can be assessed by in vivo lung deposition studies. Dry powder formulations are popular as devices are portable and aerosolisation does not require a propellant. Over the years, key advancements in dry powder formulation, device design and our understanding on the mechanics of inhaled pharmaceutical aerosol have opened up new opportunities in treatment of diseases through pulmonary drug delivery. This review covers these advancements and future directions for inhaled dry powder aerosols. PMID:24818765

Yang, Michael Yifei; Chan, John Gar Yan; Chan, Hak-Kim

2014-11-10

141

Biodegradable injectable in situ forming drug delivery systems  

Microsoft Academic Search

The ability to inject a drug incorporated into a polymer to a localized site and have the polymer form a semi-solid drug depot has a number of advantages. Among these advantages is ease of application and localized, prolonged drug delivery. For these reasons a large number of in situ setting polymeric delivery systems have been developed and investigated for use

A Hatefi; B Amsden

2002-01-01

142

Expert Review Functionalized Micellar Systems for Cancer Targeted Drug Delivery  

E-print Network

Expert Review Functionalized Micellar Systems for Cancer Targeted Drug Delivery Damon Sutton,1, and general use of micelles as drug delivery systems (4Y13). The purpose of this review is to provide stability, ability to solubilize water insoluble anticancer drugs, and prolonged blood circulation times

Gao, Jinming

143

Functionalization of protein-based nanocages for drug delivery applications  

NASA Astrophysics Data System (ADS)

Traditional drug delivery strategies involve drugs which are not targeted towards the desired tissue. This can lead to undesired side effects, as normal cells are affected by the drugs as well. Therefore, new systems are now being developed which combine targeting functionalities with encapsulation of drug cargo. Protein nanocages are highly promising drug delivery platforms due to their perfectly defined structures, biocompatibility, biodegradability and low toxicity. A variety of protein nanocages have been modified and functionalized for these types of applications. In this review, we aim to give an overview of different types of modifications of protein-based nanocontainers for drug delivery applications.

Schoonen, Lise; van Hest, Jan C. M.

2014-06-01

144

Intrathecal Drug Delivery (ITDD) systems for cancer pain  

PubMed Central

Intrathecal drug delivery is an effective pain management option for patients with chronic and cancer pain. The delivery of drugs into the intrathecal space provides superior analgesia with smaller doses of analgesics to minimize side effects while significantly improving quality of life. This article aims to provide a general overview of the use of intrathecal drug delivery to manage pain, dosing recommendations, potential risks and complications, and growing trends in the field. PMID:24555051

Bhatia, Gaurav; Lau, Mary E; Koury, Katharine M; Gulur, Padma

2014-01-01

145

Lipoidal Soft Hybrid Biocarriers of Supramolecular Construction for Drug Delivery  

PubMed Central

Lipid-based innovations have achieved new heights during the last few years as an essential component of drug development. The current challenge of drug delivery is liberation of drug agents at the right time in a safe and reproducible manner to a specific target site. A number of novel drug delivery systems has emerged encompassing various routes of administration, to achieve controlled and targeted drug delivery. Microparticulate lipoidal vesicular system represents a unique technology platform suitable for the oral and systemic administration of a wide variety of molecules with important therapeutic biological activities, including drugs, genes, and vaccine antigens. The success of liposomes as drug carriers has been reflected in a number of liposome-based formulations, which are commercially available or are currently undergoing clinical trials. Also, novel lipid carrier-mediated vesicular systems are originated. This paper has focused on the lipid-based supramolecular vesicular carriers that are used in various drug delivery and drug targeting systems. PMID:22888455

Kumar, Dinesh; Sharma, Deepak; Singh, Gurmeet; Singh, Mankaran; Rathore, Mahendra Singh

2012-01-01

146

Vascular Permeability and Drug Delivery in Cancers  

PubMed Central

The endothelial barrier strictly maintains vascular and tissue homeostasis, and therefore modulates many physiological processes such as angiogenesis, immune responses, and dynamic exchanges throughout organs. Consequently, alteration of this finely tuned function may have devastating consequences for the organism. This is particularly obvious in cancers, where a disorganized and leaky blood vessel network irrigates solid tumors. In this context, vascular permeability drives tumor-induced angiogenesis, blood flow disturbances, inflammatory cell infiltration, and tumor cell extravasation. This can directly restrain the efficacy of conventional therapies by limiting intravenous drug delivery. Indeed, for more effective anti-angiogenic therapies, it is now accepted that not only should excessive angiogenesis be alleviated, but also that the tumor vasculature needs to be normalized. Recovery of normal state vasculature requires diminishing hyperpermeability, increasing pericyte coverage, and restoring the basement membrane, to subsequently reduce hypoxia, and interstitial fluid pressure. In this review, we will introduce how vascular permeability accompanies tumor progression and, as a collateral damage, impacts on efficient drug delivery. The molecular mechanisms involved in tumor-driven vascular permeability will next be detailed, with a particular focus on the main factors produced by tumor cells, especially the emblematic vascular endothelial growth factor. Finally, new perspectives in cancer therapy will be presented, centered on the use of anti-permeability factors and normalization agents. PMID:23967403

Azzi, Sandy; Hebda, Jagoda K.; Gavard, Julie

2013-01-01

147

Design of a Smart Transdermal Insulin Drug Delivery System  

Microsoft Academic Search

In this paper, a micro-needle array combined with transdermal delivery, as well as the detection of micro-sensors intelligent transdermal insulin delivery systems was designed with characteristics of pain-free, smart, timing, positioning, quantitative drug delivery. Transdermal delivery of the requirements for the design of the transdermal delivery of the microneedle array structure, and UV-LIGA process for the production of polymer micro-needle

Zhenqing Hou; Chenghong Lin; Qiqing Zhang

2010-01-01

148

Polymeric carriers: role of geometry in drug delivery  

PubMed Central

The unique properties of synthetic nanostructures promise a diverse set of applications as carriers for drug delivery, which are advantageous in terms of biocompatibility, pharmacokinetics, targeting and controlled drug release. Historically, more traditional drug delivery systems have focused on spherical carriers. However, there is a growing interest in pursuing non-spherical carriers, such as elongated or filamentous morphologies, now available due to novel formulation strategies. Unique physiochemical properties of these supramolecular structures offer distinct advantages as drug delivery systems. In particular, results of recent studies in cell cultures and lab animals indicate that rational design of carriers of a given geometry (size and shape) offers an unprecedented control of their longevity in circulation and targeting to selected cellular and subcellular locations. This article reviews drug delivery aspects of non-spherical drug delivery systems, including material selection and formulation, drug loading and release, biocompatibility, circulation behavior, targeting and subcellular addressing. PMID:19040392

Simone, Eric A; Dziubla, Thomas D; Muzykantov, Vladimir R

2009-01-01

149

Controlled drug delivery systems: past forward and future back.  

PubMed

Controlled drug delivery technology has progressed over the last six decades. This progression began in 1952 with the introduction of the first sustained release formulation. The 1st generation of drug delivery (1950-1980) focused on developing oral and transdermal sustained release systems and establishing controlled drug release mechanisms. The 2nd generation (1980-2010) was dedicated to the development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was largely focused on studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role in the 2nd generation of drug delivery technologies, and it will continue playing a leading role in the next generation. The best path towards a productive 3rd generation of drug delivery technology requires an honest, open dialog without any preconceived ideas of the past. The drug delivery field needs to take a bold approach to designing future drug delivery formulations primarily based on today's necessities, to produce the necessary innovations. The JCR provides a forum for sharing the new ideas that will shape the 3rd generation of drug delivery technology. PMID:24794901

Park, Kinam

2014-09-28

150

Is nanotechnology a boon for oral drug delivery?  

PubMed

The oral route for drug delivery is regarded as the optimal route for achieving therapeutic benefits owing to increased patient compliance. Despite phenomenal advances in injectable, transdermal, nasal and other routes of administration, the reality is that oral drug delivery remains well ahead of the pack as the preferred delivery route. Nanocarriers can overcome the major challenges associated with this route of administration: mainly poor solubility, stability and biocompatibility of drugs. This review focuses on the potential of various polymeric drug delivery systems in oral administration, their pharmacokinetics, in vitro and in vivo models, toxicity and regulatory aspects. PMID:24786464

Agrawal, Udita; Sharma, Rajeev; Gupta, Madhu; Vyas, Suresh P

2014-10-01

151

Emergency delivery of Vasopressin from an implantable MEMS rapid drug delivery device  

E-print Network

An implantable rapid drug delivery device based on micro-electro-mechanical systems (MEMS) technology was designed, fabricated and validated for the in vivo rapid delivery of vasopressin in a rabbit model. In vitro ...

Ho Duc, Hong Linh, 1978-

2009-01-01

152

Delivery of neuroactive peptide drugs to the brain via intranasal delivery  

E-print Network

1School of Molecular and Microbial Sciences, The University of Queensland, Australia. Introduction A technique to study the delivery of neuroactive drugs to the brain via nasal delivery involves the addition of the radioactive label 3H3C...

Cros, C. D.; Toth, I.; Blanchfield, J.

2006-10-27

153

Microencapsulation: A promising technique for controlled drug delivery.  

PubMed

MICROPARTICLES OFFER VARIOUS SIGNIFICANT ADVANTAGES AS DRUG DELIVERY SYSTEMS, INCLUDING: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed. PMID:21589795

Singh, M N; Hemant, K S Y; Ram, M; Shivakumar, H G

2010-07-01

154

Nanoscale coordination polymers for anticancer drug delivery  

NASA Astrophysics Data System (ADS)

This dissertation reports the synthesis and characterization of nanoscale coordination polymers (NCPs) for anticancer drug delivery. Nanoparticles have been explored in order to address the limitations of small molecule chemotherapeutics. NCPs have been investigated as drug delivery vehicles as they can exhibit the same beneficial properties as the bulk metal-organic frameworks as well as interesting characteristics that are unique to nanomaterials. Gd-MTX (MTX = methotrexate) NCPs with a MTX loading of 71.6 wt% were synthesized and stabilized by encapsulation within a lipid bilayer containing anisamide (AA), a small molecule that targets sigma receptors which are overexpressed in many cancer tissues. Functionalization with AA allows for targeted delivery and controlled release to cancer cells, as shown by enhanced efficacy against leukemia cells. The NCPs were doped with Ru(bpy)32+ (bpy = 2,2'-bipyridine), and this formulation was utilized as an optical imaging agent by confocal microscopy. NCPs containing the chemotherapeutic pemetrexed (PMX) were synthesized using different binding metals. Zr-based materials could not be stabilized by encapsulation with a lipid bilayer, and Gd-based materials showed that PMX had degraded during synthesis. However, Hf-based NCPs containing 19.7 wt% PMX were stabilized by a lipid coating and showed in vitro efficacy against non-small cell lung cancer (NSCLC) cell lines. Enhanced efficacy was observed for formulations containing AA. Additionally, NCP formulations containing the cisplatin prodrug disuccinatocisplatin were prepared; one of these formulations could be stabilized by encapsulation within a lipid layer. Coating with a lipid layer doped with AA rendered this formulation an active targeting agent. The resulting formulation proved more potent than free cisplatin in NSCLC cell lines. Improved NCP uptake was demonstrated by confocal microscopy and competitive binding assays. Finally, a Pt(IV) oxaliplatin prodrug was synthesized and incorporated in different NCPs using various binding metals. A moderate drug loading of 44.9 wt% was determined for Zr-based NCPs. This drug loading, along with a diameter less than 200 nm, make these particles promising candidates for further stabilization via lipid encapsulation.

Phillips, Rachel Huxford

155

Nanomicellar formulations for sustained drug delivery: strategies and underlying principles  

PubMed Central

Micellar delivery systems smaller than 100 nm can be readily prepared. While micelles allow a great depth of tissue penetration for targeted drug delivery, they usually disintegrate rapidly in the body. Thus, sustained drug delivery from micellar nanocarriers is a challenge. This article summarizes various key strategies and underlying principles for sustained drug delivery using micellar nanocarriers. Comparisons are made with other competing delivery systems such as polymeric microparticles and nanoparticles. Amphiphilic molecules self-assemble in appropriate liquid media to form nanoscale micelles. Strategies for sustained release nanomicellar carriers include use of prodrugs, drug polymer conjugates, novel polymers with low critical micellar concentration or of a reverse thermoresponsive nature, reverse micelles, multi-layer micelles with layer by layer assembly, polymeric films capable of forming micelles in vivo and micelle coats on a solid support. These new micellar systems are promising for sustained drug delivery. PMID:20394539

Trivedi, Ruchit; Kompella, Uday B

2010-01-01

156

Amphiphilic linear-dendritic block copolymers for drug delivery  

E-print Network

Polymeric drug delivery systems have been widely used in the pharmaceutical industry. Such systems can solubilize and sequester hydrophobic drugs from degradation, thereby increasing circulation half-life and efficacy. ...

Nguyen, Phuong, Ph. D. Massachusetts Institute of Technology

2007-01-01

157

Enzyme-responsive nanomaterials for controlled drug delivery  

NASA Astrophysics Data System (ADS)

Enzymes underpin physiological function and exhibit dysregulation in many disease-associated microenvironments and aberrant cell processes. Exploiting altered enzyme activity and expression for diagnostics, drug targeting, and drug release is tremendously promising. When combined with booming research in nanobiotechnology, enzyme-responsive nanomaterials used for controlled drug release have achieved significant development and have been studied as an important class of drug delivery strategies in nanomedicine. In this review, we describe enzymes such as proteases, phospholipases and oxidoreductases that serve as delivery triggers. Subsequently, we explore recently developed enzyme-responsive nanomaterials with versatile applications for extracellular and intracellular drug delivery. We conclude by discussing future opportunities and challenges in this area.

Hu, Quanyin; Katti, Prateek S.; Gu, Zhen

2014-10-01

158

Engineering bioceramic microstructure for customized drug delivery  

NASA Astrophysics Data System (ADS)

One of the most efficient approaches to treat cancer and infection is to use biomaterials as a drug delivery system (DDS). The goal is for the material to provide a sustained release of therapeutic drug dose locally to target the ill tissue without affecting other organs. Silica Calcium Phosphate nano composite (SCPC) is a drug delivery platform that successfully demonstrated the ability to bind and release several therapeutics including antibiotics, anticancer drugs, and growth factors. The aim of the present work is to analyze the role of SCPC microstructure on drug binding and release kinetics. The main crystalline phases of SCPC are alpha-cristobalite (SiO2, Cris) and beta-rhenanite (NaCaPO4, Rhe); therefore, these two phases were prepared and characterized separately. Structural and compositional features of Cris, Rhe and SCPC bioceramics demonstrated a significant influence on the loading capacity and release kinetics profile of Vancomycin (Vanc) and Cisplatin (Cis). Fourier Transform Infrared (FTIR) spectroscopy analyses demonstrated that the P-O functional group in Rhe and SCPC has high affinity to the (C=O and N-H) of Vanc and (N-H and O-H) of Cis. By contrast, a weak chemical interaction between the Si-O functional group in Cris and SCPC and the two drugs was observed. Vanc loading per unit surface area increased in the order 8.00 microg Vanc/m2 for Rhe > 4.49 microg Vanc /m2 for SCPC>3.01 microg Vanc /m2 for Cris (p<0.05). Cis loading capacity increased in the order 8.59 microg Vanc /m2 for Cris, 17.8 microg Vanc/m2 for Rhe and 6.03 microg Vanc /m2 for SCPC (p<0.05). Drug release kinetics was dependent on the carrier as well as on the kind of drug. Different burst release and sustained release rates were measured for Vanc and Cis from the same carrier. The percentages of drug amount released from Cris, Rhe and SCPC during the burst stage (the first 2h) were: 50%, 50%, and 46% of Vanc; and 53.4%, 36.6%, and 30.6 % of Cis, respectively. Burst release was found to correlate with the pore size distribution and surface area. Furthermore, the average rates of sustained release in the period 8-216h from Cris, Rhe and SCPC were: 9.8, 7.2 and 3.5 mug/h of Vanc and 4.5, 5.3 and 3.5 mug/h of Cis, respectively. Nearly inert Cris ceramic showed release kinetics controlled by its hierarchical nano porous structure. On the other hand, the phase composition and surface chemistry of bioactive Rhe or SCPC ceramics overruled the effect of surface area. The relatively low rate of drug release from SCPC was due to the dissolution-back precipitation reaction taking place on the material surface as confirmed by FTIR bands of surface hydroxyapatite layer at 576.5, 596.7 and 620.7 cm-1. Moreover, the solid solution of crystalline phases of SCPC enhanced the bioactivity of the composite. Nuclear Magnetic Resonance (NMR) and cell culture analyses demonstrated that the interactions between the SCPC dissolution products and the released drug did not cause measurable negative effects on the bioactivity of the tested drugs. The therapeutic effects of the SCPC-Cis hybrid were evaluated using a rat model of hepatocellular carcinoma (HCC). Animals were treated by either systemic cisplatin injection (sCis), or with SCPC-Cis hybrid placed adjacent (ADJ) to, or within (IT), the tumor. Five days after implantation 50-55% of the total cisplatin loaded was released from the SCPC-Cis hybrids resulting in an approximately 50% decrease in tumor volume compared to sCis treatment. Severe side effects were observed in animals treated with sCis including rapid weight loss and decreased liver and kidney function, effects not observed in SCPC-Cis treated animals. Analysis of cisplatin distribution demonstrated drug concentrations in the tumor were 21 and 1.5-times higher in IT and ADJ groups, respectively, as compared to sCis treated animals. These data demonstrate the SCPC drug delivery system can provide an effective localized treatment for HCC with significantly reduced toxicity compared to systemic drug administration. Moreover, it is pos

Pacheco Gomez, Hernando Jose

159

Advances in Lymphatic Imaging and Drug Delivery  

SciTech Connect

Cancer remains the second leading cause of death after heart disease in the US. While metastasized cancers such as breast, prostate, and colon are incurable, before their distant spread, these diseases will have invaded the lymphatic system as a first step in their progression. Hence, proper evaluation of the disease state of the lymphatics which drain a tumor site is crucial to staging and the formation of a treatment plan. Current lymphatic imaging modalities with visible dyes and radionucleotide tracers offer limited sensitivity and poor resolution; however, newer tools using nanocarriers, quantum dots, and magnetic resonance imaging promise to vastly improve the staging of lymphatic spread without needless biopsies. Concurrent with the improvement of lymphatic imaging agents, has been the development of drug carriers that can localize chemotherapy to the lymphatic system, thus improving the treatment of localized disease while minimizing the exposure of healthy organs to cytotoxic drugs. This review will focus on polymeric systems that have been developed for imaging and drug delivery to the lymph system, how these new devices improve upon current technologies, and where further improvement is needed.

Nune, Satish K.; Gunda, Padmaja; Majeti, Bharat K.; Thallapally, Praveen K.; Laird, Forrest M.

2011-09-10

160

Polymeric Microgels as Potential Drug Delivery Vesicles  

NASA Astrophysics Data System (ADS)

The temperature dependent volume phase change of cross-linked amphiphilic molecules (microgels) suggests their use as drug delivery vesicles. Drug particles aggregate in the slightly hydrophobic microgel interior. They are stored in equilibrium until the critical temperature (Tv) is reached where the volume phase change limits available space, thus expelling the drugs. This loading property of hydroxypropylcellulose (HPC) microgels was tested using amperometric analytical techniques. Small molecules inside microgels do not approach the electrode surface, which decreases current signal. A room temperature (Troom) flow amperometric measurement comparing microgel/paracetamol solution with control paracetamol samples yielded about 20 percent concentration reduction in the microgel sample. Results from the steady-state electrochemical experiment confirm the 20 percent concentration drop in the microgel sample compared to the control sample at Troom. Using the steady-state experiment with a cyclic temperature ramp from Troom to beyond Tv showed that the paracetamol concentration change between the temperature extremes was greater for the microgels than for the controls. An evolving aspect of the study is the characterization of microgel shrinkage from in situ, temperature controlled liquid AFM images as compared to previously completed DLS characterization of the same microgel sample.

McDonough, Ryan; Streletzky, Kiril; Bayachou, Mekki; Peiris, Pubudu

2010-03-01

161

Dendrimeric Drug Delivery Agents Interacting with Membranes  

NASA Astrophysics Data System (ADS)

New initiatives in cancer treatment try to improve chemotherapy by developing smart drug delivery vehicles. The goal is to specifically target a tumor and deliver a therapeutic to kill it without causing damage to healthy tissue. A promising class of nanomaterials that can serve as a platform for this purpose is dendritic polymers, or dendrimers. In order to reach a high degree of specificity it is crucial to understand the details of the uptake of the polymer through the cell membrane. For this study the interactions of PAMAM dendrimers with model membranes consisting of DMPC bilayers are observed in real time using AFM. We compare dendrimers with various functional groups, sizes and architectures and show how these factors influence their effect on the lipid bilayer.

Mecke, Almut; Banszak Holl, Mark; Orr, Bradford; Patri, Anil K.; Lee, Inhan; Baker, James, Jr.

2002-03-01

162

Drug delivery by organ-specific immunoliposomes  

SciTech Connect

Monoclonal antibodies highly specific to the mouse pulmonary endothelial cells were conjugated to liposomes. The resulting immunoliposomes showed high levels of lung accumulation when injected intravenously into mice. Optimal target binding and retention were achieved if the lipid composition included ganglioside GM{sub 1} to reduce the uptake of immunoliposomes by the reticuloendothelial system. Details of the construction and optimization of these organ-specific immunoliposomes are reviewed. The drug delivery potential of this novel liposome system was demonstrated in an experimental pulmonary metastasis model. Immunoliposomes containing a lipophilic prodrug of deoxyfluorouridine effectively prolonged the survival time of the tumor-bearing mice. This and other therapeutic applications of the immunoliposomes are discussed. 25 refs., 5 figs.

Maruyama, Kazuo; Mori, Atsuhide; Hunag, Leaf (Tennessee Univ., Knoxville, TN (USA). Dept. of Biochemistry); Kennel, S.J. (Oak Ridge National Lab., TN (USA))

1990-01-01

163

Click chemistry for drug delivery nanosystems.  

PubMed

The purpose of this Expert Review is to discuss the impact of click chemistry in nanosized drug delivery systems. Since the introduction of the click concept by Sharpless and coworkers in 2001, numerous examples of click reactions have been reported for the preparation and functionalization of polymeric micelles and nanoparticles, liposomes and polymersomes, capsules, microspheres, metal and silica nanoparticles, carbon nanotubes and fullerenes, or bionanoparticles. Among these click processes, Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) has attracted most attention based on its high orthogonality, reliability, and experimental simplicity for non-specialists. A renewed interest in the use of efficient classical transformations has been also observed (e.g., thiol-ene coupling, Michael addition, Diels-Alder). Special emphasis is also devoted to critically discuss the click concept, as well as practical aspects of application of CuAAC to ensure efficient and harmless bioconjugation. PMID:21913032

Lallana, Enrique; Sousa-Herves, Ana; Fernandez-Trillo, Francisco; Riguera, Ricardo; Fernandez-Megia, Eduardo

2012-01-01

164

Pharmacosomes: an emerging novel vesicular drug delivery system for poorly soluble synthetic and herbal drugs.  

PubMed

In the arena of solubility enhancement, several problems are encountered. A novel approach based on lipid drug delivery system has evolved, pharmacosomes. Pharmacosomes are colloidal, nanometric size micelles, vesicles or may be in the form of hexagonal assembly of colloidal drug dispersions attached covalently to the phospholipid. They act as befitting carrier for delivery of drugs quite precisely owing to their unique properties like small size, amphiphilicity, active drug loading, high entrapment efficiency, and stability. They help in controlled release of drug at the site of action as well as in reduction in cost of therapy, drug leakage and toxicity, increased bioavailability of poorly soluble drugs, and restorative effects. There has been advancement in the scope of this delivery system for a number of drugs used for inflammation, heart diseases, cancer, and protein delivery along with a large number of herbal drugs. Hence, pharmacosomes open new challenges and opportunities for improved novel vesicular drug delivery system. PMID:24106615

Pandita, Archana; Sharma, Pooja

2013-01-01

165

Nanoparticle-based drug delivery to the vagina: a review.  

PubMed

Vaginal drug administration can improve prophylaxis and treatment of many conditions affecting the female reproductive tract, including sexually transmitted diseases, fungal and bacterial infections, and cancer. However, achieving sustained local drug concentrations in the vagina can be challenging, due to the high permeability of the vaginal epithelium and expulsion of conventional soluble drug dosage forms. Nanoparticle-based drug delivery platforms have received considerable attention for vaginal drug delivery, as nanoparticles can provide sustained release, cellular targeting, and even intrinsic antimicrobial or adjuvant properties that can improve the potency and/or efficacy of prophylactic and therapeutic modalities. Here, we review the use of polymeric nanoparticles, liposomes, dendrimers, and inorganic nanoparticles for vaginal drug delivery. Although most of the work toward nanoparticle-based drug delivery in the vagina has been focused on HIV prevention, strategies for treatment and prevention of other sexually transmitted infections, treatment for reproductive tract cancer, and treatment of fungal and bacterial infections are also highlighted. PMID:24830303

Ensign, Laura M; Cone, Richard; Hanes, Justin

2014-09-28

166

Subcellular targeting strategies for drug design and delivery  

Microsoft Academic Search

Many drug targets are localized to particular subcellular compartments, yet current drug design strategies are focused on bioavailability and tissue targeting and rarely address drug delivery to specific intracellular compartments. Insights into how the cell traffics its constituents to these different cellular locations could improve drug design. In this Review, we explore the fundamentals of membrane trafficking and subcellular organization,

Lawrence Rajendran; Hans-Joachim Knölker; Kai Simons

2010-01-01

167

Enhanced drug delivery capabilities from stents coated with absorbable polymer and crystalline drug  

E-print Network

Current drug eluting stent (DES) technology is not optimized with regard to the pharmacokinetics of drug delivery. A novel, absorbable-coating sirolimus-eluting stent (AC-SES) was evaluated for its capacity to deliver drug ...

Carlyle, Wenda C.

168

Biocompatibility and biofouling of MEMS drug delivery devices  

Microsoft Academic Search

The biocompatibility and biofouling of the microfabrication materials for a MEMS drug delivery device have been evaluated. The in vivo inflammatory and wound healing response of MEMS drug delivery component materials, metallic gold, silicon nitride, silicon dioxide, silicon, and SU-8TM photoresist, were evaluated using the cage implant system. Materials, placed into stainless-steel cages, were implanted subcutaneously in a rodent model.

Gabriela Voskerician; Matthew S. Shive; Rebecca S. Shawgo; Horst von Recum; James M. Anderson; Michael J. Cima; Robert Langer

2003-01-01

169

Perspectives on the Interface of Drug Delivery and Tissue Engineering  

PubMed Central

Controlled drug delivery of bioactive molecules continues to be an essential component of engineering strategies for tissue defect repair. This article surveys the current challenges associated with trying to regenerate complex tissues utilizing drug delivery and gives perspectives on the development of translational tissue engineering therapies which promote spatiotemporal cell-signaling cascades to maximize the rate and quality of repair. PMID:23000743

Ekenseair, Adam K.; Kasper, F. Kurtis; Mikos, Antonios G.

2012-01-01

170

Small-scale systems for in vivo drug delivery  

Microsoft Academic Search

Recent developments in the application of micro- and nanosystems for drug administration include a diverse range of new materials and methods. New approaches include the on-demand activation of molecular interactions, novel diffusion-controlled delivery devices, nanostructured 'smart' surfaces and materials, and prospects for coupling drug delivery to sensors and implants. Micro- and nanotechnologies are enabling the design of novel methods such

David A LaVan; Terry McGuire; Robert Langer

2003-01-01

171

Microemulsion-based media as novel drug delivery systems  

Microsoft Academic Search

Microemulsions are clear, stable, isotropic mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating a wide range of drug molecules. In order to appreciate the potential of microemulsions as delivery vehicles, this review gives

M. Jayne Lawrence; Gareth D. Rees

2000-01-01

172

Current status and future potential of transdermal drug delivery  

Microsoft Academic Search

The past twenty five years have seen an explosion in the creation and discovery of new medicinal agents. Related innovations in drug delivery systems have not only enabled the successful implementation of many of these novel pharmaceuticals, but have also permitted the development of new medical treatments with existing drugs. The creation of transdermal delivery systems has been one of

Mark R. Prausnitz; Samir Mitragotri; Robert Langer

2004-01-01

173

A PARYLENE BELLOWS ELECTROCHEMICAL ACTUATOR FOR INTRAOCULAR DRUG DELIVERY  

E-print Network

A PARYLENE BELLOWS ELECTROCHEMICAL ACTUATOR FOR INTRAOCULAR DRUG DELIVERY P.-Y. Li1* , R. Sheybani2 California, Los Angeles, California, USA ABSTRACT The first electrochemical actuator with a Parylene bellows for intraocular drug delivery is presented in which the bellows separates the electrolysis actuation chamber from

Meng, Ellis

174

Clinical Applications of Biomedical Microdevices for Controlled Drug Delivery.  

PubMed

Miniaturization of devices to micrometer and nanometer scales, combined with the use of biocompatible and functional materials, has created new opportunities for the implementation of drug delivery systems. Advances in biomedical microdevices for controlled drug delivery platforms promise a new generation of capabilities for the treatment of acute conditions and chronic illnesses, which require high adherence to treatment, in which temporal control over the pharmacokinetic profiles is critical. In addition, clinical conditions that require a combination of drugs with specific pharmacodynamic profiles and local delivery will benefit from drug delivery microdevices. This review provides a summary of various clinical applications for state-of-the-art controlled drug delivery microdevices, including cancer, endocrine and ocular disorders, and acute conditions such as hemorrhagic shock. Regulatory considerations for clinical translation of drug delivery microdevices are also discussed. Drug delivery microdevices promise a remarkable gain in clinical outcomes and a substantial social impact. A review of articles covering the field of microdevices for drug delivery was performed between January 1, 1990, and January 1, 2014, using PubMed as a search engine. PMID:25484235

Gurman, Pablo; Miranda, Oscar R; Clayton, Kevin; Rosen, Yitzhak; Elman, Noel M

2014-12-01

175

Development of a Microfluidics-Based Intracochlear Drug Delivery Device  

Microsoft Academic Search

Background: Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration. Methods: We have taken a microfluidics\\/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating inner-ear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the

William F. Sewell; Jeffrey T. Borenstein; Zhiqiang Chen; Jason Fiering; Ophir Handzel; Maria Holmboe; Ernest S. Kim; Sharon G. Kujawa; Michael J. McKenna; Mark M. Mescher; Brian Murphy; Erin E. Leary Swan; Marcello Peppi; Sarah Tao

2009-01-01

176

Biodegradable polymer droplet for efficient drug delivery using flagellated bacteria  

Microsoft Academic Search

This paper presents a biodegradable polymer droplet for efficient drug delivery using flagellated bacteria. The biodegradability and the localized delivery are the most important features for determining the efficiency of drug delivery. The proposed droplet is made of poly (DL-lactic-co-glycolic acid) for the biodegradability. It is fabricated using a microfluidic device which has a Y-junction microchannel. The fabricated biodegradable droplet

Seok-jun Hong; Kyo-in Koo; Sang-min Lee; Ho-soo Park; Hyung-jung Yoo; Joonhwuy Kim

2010-01-01

177

Novel Approaches in Formulation and Drug Delivery using Contact Lenses  

PubMed Central

The success of ocular delivery relies on the potential to enhance the drug bioavailability by controlled and extended release of drug on the eye surface. Several new approaches have been attempted to augment the competence and diminish the intrinsic side effects of existing ocular drug delivery systems. In this contest, progress has been made to develop drug-eluting contact lens using different techniques, which have the potential to control and sustain the delivery of drug. Further, the availability of novel polymers have facilitated and promoted the utility of contact lenses in ocular drug delivery. Several research groups have already explored the feasibility and potential of contact lens using conventional drugs for the treatment of periocular and intraocular diseases. Contact lenses formulated using modern technology exhibits high loading, controlled drug release, apposite thickness, water content, superior mechanical and optical properties as compared to commercial lenses. In general, this review discus various factors and approaches designed and explored for the successful delivery of ophthalmic drugs using contact lenses as drug delivery device PMID:24826007

Singh, Kishan; Nair, Anroop B; Kumar, Ashok; Kumria, Rachna

2011-01-01

178

Prodrug-based nanoparticulate drug delivery strategies for cancer therapy.  

PubMed

Despite the rapid developments in nanotechnology and biomaterials, the efficient delivery of chemotherapeutic agents is still challenging. Prodrug-based nanoassemblies have many advantages as a potent platform for anticancer drug delivery, such as improved drug availability, high drug loading efficiency, resistance to recrystallization upon encapsulation, and spatially and temporally controllable drug release. In this review, we discuss prodrug-based nanocarriers for cancer therapy, including nanosystems based on polymer-drug conjugates, self-assembling small molecular weight prodrugs and prodrug-encapsulated nanoparticles (NPs). In addition, we discuss new trends in the field of prodrug-based nanoassemblies that enhance the delivery efficiency of anticancer drugs, with special emphasis on smart stimuli-triggered drug release, hybrid nanoassemblies, and combination drug therapy. PMID:25441774

Luo, Cong; Sun, Jin; Sun, Bingjun; He, Zhonggui

2014-11-01

179

NanoART, neuroAIDS and CNS drug delivery  

PubMed Central

A broad range of nanomedicines is being developed to improve drug delivery for CNS disorders. The structure of the blood–brain barrier (BBB), the presence of efflux pumps and the expression of metabolic enzymes pose hurdles for drug-brain entry. Nanoformulations can circumvent the BBB to improve CNS-directed drug delivery by affecting such pumps and enzymes. Alternatively, they can be optimized to affect their size, shape, and protein and lipid coatings to facilitate drug uptake, release and ingress across the barrier. This is important as the brain is a sanctuary for a broad range of pathogens including HIV-1. Improved drug delivery to the CNS would affect pharmacokinetic and drug biodistribution properties. This article focuses on how nanotechnology can serve to improve the delivery of antiretroviral medicines, termed nanoART, across the BBB and affect the biodistribution and clinical benefit for HIV-1 disease. PMID:19572821

Nowacek, Ari; Gendelman, Howard E

2009-01-01

180

Polymeric Nanoparticles for Drug Delivery Juliana M. Chan, Pedro M. Valencia, Liangfang Zhang,  

E-print Network

Chapter 11 Polymeric Nanoparticles for Drug Delivery Juliana M. Chan, Pedro M. Valencia, Liangfang (NPs) for controlled drug delivery has shown sig- nificant therapeutic potential. Concurrently nanoparticles, polymer conjugation chemistry, targeted drug delivery, sur- face functionalization, aptamers

Zhang, Liangfang

181

Silk-based biomaterials for sustained drug delivery.  

PubMed

Silk presents a rare combination of desirable properties for sustained drug delivery, including aqueous-based purification and processing options without chemical cross-linkers, compatibility with common sterilization methods, controllable and surface-mediated biodegradation into non-inflammatory by-products, biocompatibility, utility in drug stabilization, and robust mechanical properties. A versatile silk-based toolkit is currently available for sustained drug delivery formulations of small molecule through macromolecular drugs, with a promise to mitigate several drawbacks associated with other degradable sustained delivery technologies in the market. Silk-based formulations utilize silk's well-defined nano- through microscale structural hierarchy, stimuli-responsive self-assembly pathways and crystal polymorphism, as well as sequence and genetic modification options towards targeted pharmaceutical outcomes. Furthermore, by manipulating the interactions between silk and drug molecules, near-zero order sustained release may be achieved through diffusion- and degradation-based release mechanisms. Because of these desirable properties, there has been increasing industrial interest in silk-based drug delivery systems currently at various stages of the developmental pipeline from pre-clinical to FDA-approved products. Here, we discuss the unique aspects of silk technology as a sustained drug delivery platform and highlight the current state of the art in silk-based drug delivery. We also offer a potential early development pathway for silk-based sustained delivery products. PMID:24910193

Yucel, Tuna; Lovett, Michael L; Kaplan, David L

2014-09-28

182

Intraperiodontal pocket: An ideal route for local antimicrobial drug delivery  

PubMed Central

Periodontal pockets act as a natural reservoir filled with gingival crevicular fluid for the controlled release delivery of antimicrobials directly. This article reflects the present status of nonsurgical controlled local intrapocket delivery of antimicrobials in the treatment of periodontitis. These sites have specialty in terms of anatomy, permeability, and their ability to retain a delivery system for a desired length of time. A number of antimicrobial products and the composition of the delivery systems, its use, clinical results, and their release are summarized. The goal in using an intrapocket device for the delivery of an antimicrobial agent is the achievement and maintenance of therapeutic drug concentration for the desired period of time. Novel controlled drug delivery system are capable of improving patient compliance as well as therapeutic efficacy with precise control of the rate by which a particular drug dosage is released from a delivery system without the need for frequent administration. These are considered superior drug delivery system because of low cost, greater stability, non-toxicity, biocompatibility, non-immunogenicity, and are biodegradable in nature. This review also focus on the importance and ideal features of periodontal pockets as a drug delivery platform for designing a suitable dosage form along with its potential advantage and limitations. The microbes in the periodontal pocket could destroy periodontal tissues, and a complete knowledge of these as well as an ideal treatment strategy could be helpful in treating this disease. PMID:22470888

Nair, Sreeja C.; Anoop, K. R.

2012-01-01

183

Polymer nanogels: a versatile nanoscopic drug delivery platform  

PubMed Central

In this review we put the spotlight on crosslinked polymer nanogels, a promising platform that has the characteristics of an “ideal” drug delivery vehicle. Some of the key aspects of drug delivery vehicle design like stability, response to biologically relevant stimuli, passive targeting, active targeting, toxicity and ease of synthesis are discussed. We discuss several delivery systems in this light and highlight some examples of systems, which satisfy some or all of these design requirements. In particular, we point to the advantages that crosslinked polymeric systems bring to drug delivery. We review some of the synthetic methods of nanogel synthesis and conclude with the diverse applications in drug delivery where nanogels have been fruitfully employed. PMID:22342438

Chacko, Reuben T.; Ventura, Judy; Zhuang, Jiaming; Thayumanavan, S.

2012-01-01

184

Reservoir-Based Drug Delivery Systems Utilizing Microtechnology  

PubMed Central

This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

2012-01-01

185

Layered Double Hydroxide-Based Nanocarriers for Drug Delivery  

PubMed Central

Biocompatible clay materials have attracted particular attention as the efficient drug delivery systems (DDS). In this article, we review developments in the use of layered double hydroxides (LDHs) for controlled drug release and delivery. We show how advances in the ability to synthesize intercalated structures have a significant influence on the development of new applications of these materials. We also show how modification and/or functionalization can lead to new biotechnological and biomedical applications. This review highlights the most recent progresses in research on LDH-based controlled drug delivery systems, focusing mainly on: (i) DDS with cardiovascular drugs as guests; (ii) DDS with anti-inflammatory drugs as guests; and (iii) DDS with anti-cancer drugs as guests. Finally, future prospects for LDH-based drug carriers are also discussed. PMID:24940733

Bi, Xue; Zhang, Hui; Dou, Liguang

2014-01-01

186

Bioavailability of phytochemicals and its enhancement by drug delivery systems  

PubMed Central

Issues of poor oral bioavailability of cancer chemopreventives have hindered progress in cancer prevention. Novel delivery systems that modulate the pharmacokinetics of existing drugs, such as nanoparticles, cyclodextrins, niosomes, liposomes and implants, could be used to enhance the delivery of chemopreventive agents to target sites. The development of new approaches in prevention and treatment of cancer could encompass new delivery systems for approved and newly investigated compounds. In this review, we discuss some of the delivery approaches that have already made an impact by either delivering a drug to target tissue or increasing its bioavailability by many fold. PMID:23435377

Aqil, Farrukh; Munagala, Radha; Jeyabalan, Jeyaprakash; Vadhanam, Manicka V.

2013-01-01

187

An efficient drug delivery vehicle for botulism countermeasure  

PubMed Central

Background Botulinum neurotoxin (BoNT) is the most potent poison known to mankind. Currently no antidote is available to rescue poisoned synapses. An effective medical countermeasure strategy would require developing a drug that could rescue poisoned neuromuscular synapses and include its efficient delivery specifically to poisoned presynaptic nerve terminals. Here we report a drug delivery strategy that could directly deliver toxin inhibitors into the intoxicated nerve terminal cytosol. Results A targeted delivery vehicle was developed for intracellular transport of emerging botulinum neurotoxin antagonists. The drug delivery vehicle consisted of the non-toxic recombinant heavy chain of botulinum neurotoxin-A coupled to a 10-kDa amino dextran via the heterobifunctional linker 3-(2-pyridylthio)-propionyl hydrazide. The heavy chain served to target botulinum neurotoxin-sensitive cells and promote internalization of the complex, while the dextran served as a platform to deliver model therapeutic molecules to the targeted neurons. Our results indicated that the drug delivery vehicle entry into neurons was via BoNT-A receptor mediated endocytosis. Once internalized into neurons, the drug carrier component separated from the drug delivery vehicle in a fashion similar to the separation of the BoNT-A light chain from the holotoxin. This drug delivery vehicle could be used to deliver BoNT-A antidotes into BoNT-A intoxicated cultured mouse spinal cord cells. Conclusion An effective BoNT-based drug delivery vehicle can be used to directly deliver toxin inhibitors into intoxicated nerve terminal cytosol. This approach can potentially be utilized for targeted drug delivery to treat other neuronal and neuromuscular disorders. This report also provides new knowledge of endocytosis and exocytosis as well as of BoNT trafficking. PMID:19860869

Zhang, Peng; Ray, Radharaman; Singh, Bal Ram; Li, Dan; Adler, Michael; Ray, Prabhati

2009-01-01

188

Enhanced transdermal drug delivery techniques: an extensive review of patents.  

PubMed

Transdermal drug delivery system has been accepted as potential non-invasive route of drug administration, with advantages of avoidance of the first-pass metabolism, sustained therapeutic action and better patient compliance, though, its prevalent use is restricted due to excellent impervious nature of skin. It is the greatest challenge for researchers to surmount the inherent limitations imposed by stratum corneum of skin, for enhanced transdermal drug delivery to achieve systemic therapeutic concentration. Thus, many approaches have been attempted to perturb skin barrier and enhance the transdermal delivery of drug. The major approaches for enhancing transdermal delivery are physical enhancers (ultrasound, iontophoresis, electroporation, magnetophoresis, microneedle), vesicles, particulate systems (liposome, niosome, transfersome, microemulsion, solid lipid nanoparticle) and chemical enhancers (sulphoxides, azones, glycols, alkanols, terpenes etc.). The present review explores recent patents on techniques employed to breach the skin barrier for drug permeation along with their penetration enhancement mechanisms. PMID:19519571

Rizwan, Mohammad; Aqil, Mohammad; Talegaonkar, Sushama; Azeem, Adnan; Sultana, Yasmin; Ali, Asgar

2009-06-01

189

Niosomes: a controlled and novel drug delivery system.  

PubMed

During the past decade formulation of vesicles as a tool to improve drug delivery, has created a lot of interest amongst the scientist working in the area of drug delivery systems. Vesicular system such as liposomes, niosomes, transferosomes, pharmacosomes and ethosomes provide an alternative to improve the drug delivery. Niosomes play an important role owing to their nonionic properties, in such drug delivery system. Design and development of novel drug delivery system (NDDS) has two prerequisites. First, it should deliver the drug in accordance with a predetermined rate and second it should release therapeutically effective amount of drug at the site of action. Conventional dosage forms are unable to meet these requisites. Niosomes are essentially non-ionic surfactant based multilamellar or unilamellar vesicles in which an aqueous solution of solute is entirely enclosed by a membrane resulting from the organization of surfactant macromolecules as bilayer. Niosomes are formed on hydration of non-ionic surfactant film which eventually hydrates imbibing or encapsulating the hydrating aqueous solution. The main aim of development of niosomes is to control the release of drug in a sustained way, modification of distribution profile of drug and for targeting the drug to the specific body site. This paper deals with composition, characterization/evaluation, merits, demerits and applications of niosomes. PMID:21719996

Rajera, Rampal; Nagpal, Kalpana; Singh, Shailendra Kumar; Mishra, Dina Nath

2011-01-01

190

Osmotic drug delivery using swellable-core technology  

Microsoft Academic Search

Swellable-core technology (SCT) formulations that used osmotic pressure and polymer swelling to deliver drugs to the GI tract in a reliable and reproducible manner were studied. The SCT formulations consisted of a core tablet containing the drug and a water-swellable component, and one or more delivery ports. The in vitro and in vivo performance of two model drugs, tenidap and

A. G. Thombre; L. E. Appel; M. B. Chidlaw; P. D. Daugherity; F. Dumont; L. A. F. Evans; S. C. Sutton

2004-01-01

191

A Controlled Drug-Delivery Experiment Using Alginate Beads  

ERIC Educational Resources Information Center

This paper describes a simple, cost-effective experiment which introduces students to drug delivery and modeling using alginate beads. Students produce calcium alginate beads loaded with drug and measure the rate of release from the beads for systems having different stir rates, geometries, extents of cross-linking, and drug molecular weight.…

Farrell, Stephanie; Vernengo, Jennifer

2012-01-01

192

Novel mechanisms and devices to enable successful transdermal drug delivery  

Microsoft Academic Search

Optimisation of drug delivery through human skin is important in modern therapy. This review considers drug–vehicle interactions (drug or prodrug selection, chemical potential control, ion pairs, coacervates and eutectic systems) and the role of vesicles and particles (liposomes, transfersomes, ethosomes, niosomes). We can modify the stratum corneum by hydration and chemical enhancers, or bypass or remove this tissue via microneedles,

B. W Barry

2001-01-01

193

Dendrimeric Systems and Their Applications in Ocular Drug Delivery  

PubMed Central

Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug's water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye's unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed. PMID:24396306

Yavuz, Burçin; Bozda? Pehlivan, Sibel; Ünlü, Nur?en

2013-01-01

194

Porous silicon advances in drug delivery and immunotherapy  

PubMed Central

Biomedical applications of porous silicon include drug delivery, imaging, diagnostics and immunotherapy. This review summarizes new silicon particle fabrication techniques, dynamics of cellular transport, advances in the multistage vector approach to drug delivery, and the use of porous silicon as immune adjuvants. Recent findings support superior therapeutic efficacy of the multistage vector approach over single particle drug delivery systems in mouse models of ovarian and breast cancer. With respect to vaccine development, multivalent presentation of pathogen-associated molecular patterns on the particle surface creates powerful platforms for immunotherapy, with the porous matrix able to carry both antigens and immune modulators. PMID:23845260

Savage, D; Liu, X; Curley, S; Ferrari, M; Serda, RE

2013-01-01

195

Inorganic Nanoporous Membranes for Immunoisolated Cell-Based Drug Delivery  

PubMed Central

Materials advances enabled by nanotechnology have brought about promising approaches to improve the encapsulation mechanism for immunoisolated cell-based drug delivery. Cell-based drug delivery is a promising treatment for many diseases but has thus far achieved only limited clinical success. Treatment of insulin dependent diabetes mellitus (IDDM) by transplantation of pancreatic ?-cells represents the most anticipated application of cell-based drug delivery technology. This review outlines the challenges involved with maintaining transplanted cell viability and discusses how inorganic nanoporous membranes may be useful in achieving clinical success. PMID:20384222

Mendelsohn, Adam; Desai, Tejal

2014-01-01

196

An approach to drug delivery using novel carbohydrates to carry drugs  

E-print Network

An approach to drug delivery using novel carbohydrates to carry drugs has recently been described of the cancer drug doxorubicin targeted to hepatocytes in a mouse liver tumour model. Known as the LEAPT step involves administering the rhamnose-capped pro-drug; the drug is activated in the target cell once

Davis, Ben G.

197

Drug delivery and nanodetection in lung cancer.  

PubMed

Lung carcinoma is the most widespread type of cancer worldwide, and is responsible for more deaths than other types of cancer. Lung cancer remains the chief cause of cancer-related deaths in both men and women worldwide, and is increasingly common in women. Each year, the number of deaths from lung cancer is greater than the number due to breast and colorectal cancer combined. Lung cancer accounted for 13% (1.6 million) of the total cases and 18% (1.4 million) of the deaths in 2008. In Iran, lung cancer is one of the five leading tumors. Among females, it was the fourth most commonly diagnosed cancer, and the second leading cause of cancer death. Nanotechnology can be defined as the science and engineering involved in the design, characterization, and application of materials and devices whose smallest functional organization in at least one dimension is on the nanometer scale, i.e. one billionth of a meter. It is an exciting multidisciplinary field that involves the design and engineering of nano objects or nanotools with diameters less than 500 nanometers (nm), and it is one of the most interesting fields of the 21st century. Nanotechnology also offers the ability to detect diseases, such as tumors, much earlier than ever imaginable. This article presents nano devices for lung cancer detection and drug delivery systems. PMID:25386728

Badrzadeh, Fariba; Rahmati-Yamchi, Mohammad; Badrzadeh, Kazem; Valizadeh, Alireza; Zarghami, Nosratollah; Farkhani, Samad Mussa; Akbarzadeh, Abolfazl

2014-11-11

198

Hollow Pollen Shells to Enhance Drug Delivery  

PubMed Central

Pollen grain and spore shells are natural microcapsules designed to protect the genetic material of the plant from external damage. The shell is made up of two layers, the inner layer (intine), made largely of cellulose, and the outer layer (exine), composed mainly of sporopollenin. The relative proportion of each varies according to the plant species. The structure of sporopollenin has not been fully characterised but different studies suggest the presence of conjugated phenols, which provide antioxidant properties to the microcapsule and UV (ultraviolet) protection to the material inside it. These microcapsule shells have many advantageous properties, such as homogeneity in size, resilience to both alkalis and acids, and the ability to withstand temperatures up to 250 °C. These hollow microcapsules have the ability to encapsulate and release actives in a controlled manner. Their mucoadhesion to intestinal tissues may contribute to the extended contact of the sporopollenin with the intestinal mucosa leading to an increased efficiency of delivery of nutraceuticals and drugs. The hollow microcapsules can be filled with a solution of the active or active in a liquid form by simply mixing both together, and in some cases operating a vacuum. The active payload can be released in the human body depending on pressure on the microcapsule, solubility and/or pH factors. Active release can be controlled by adding a coating on the shell, or co-encapsulation with the active inside the shell. PMID:24638098

Diego-Taboada, Alberto; Beckett, Stephen T.; Atkin, Stephen L.; Mackenzie, Grahame

2014-01-01

199

Giant Fullerenes for Target Specific Drug Delivery  

NASA Astrophysics Data System (ADS)

Carbon nano-structures, such as giant fullerenes, have a great potential for biological and medical applications. Most of the previous research is dedicated to investigate the use of fullerenes as vehicles for carrying medication which is chemisorbed on the outside surface of the fullerenes. In contrast, using fullerenes as an enclosure was largely abandoned due to the high strength of the carbon-carbon bonds which has been perceived to prevent the rupturing of the fullerene to release their cargo. We performed atomistic computations based on classical force fields that will address this perception. Specifically we explore the physics and chemistry of OH functionalized carbon based giant fullerenes with diameters from 0.72 nm (60 atoms) to 5.7 nm (3840 atoms). The preliminary results show that OH functionalization on these fullerenes is not only viable but also provides a pH sensitive release mechanism. Furthermore our current results show that carbon-carbon bonds can be broken in low energy biological environments in the presence of a flow induced strain field. These insights may have implications for target specific drug delivery in general and cancer treatment in particular.

Courtney, Robert; Kiefer, Boris

2013-03-01

200

Hollow pollen shells to enhance drug delivery.  

PubMed

Pollen grain and spore shells are natural microcapsules designed to protect the genetic material of the plant from external damage. The shell is made up of two layers, the inner layer (intine), made largely of cellulose, and the outer layer (exine), composed mainly of sporopollenin. The relative proportion of each varies according to the plant species. The structure of sporopollenin has not been fully characterised but different studies suggest the presence of conjugated phenols, which provide antioxidant properties to the microcapsule and UV (ultraviolet) protection to the material inside it. These microcapsule shells have many advantageous properties, such as homogeneity in size, resilience to both alkalis and acids, and the ability to withstand temperatures up to 250 °C. These hollow microcapsules have the ability to encapsulate and release actives in a controlled manner. Their mucoadhesion to intestinal tissues may contribute to the extended contact of the sporopollenin with the intestinal mucosa leading to an increased efficiency of delivery of nutraceuticals and drugs. The hollow microcapsules can be filled with a solution of the active or active in a liquid form by simply mixing both together, and in some cases operating a vacuum. The active payload can be released in the human body depending on pressure on the microcapsule, solubility and/or pH factors. Active release can be controlled by adding a coating on the shell, or co-encapsulation with the active inside the shell. PMID:24638098

Diego-Taboada, Alberto; Beckett, Stephen T; Atkin, Stephen L; Mackenzie, Grahame

2014-01-01

201

The 2nd Annual Irish Drug Delivery Network Conference with UK and Ireland Controlled Release Society: advancing drug delivery.  

PubMed

This meeting was part funded by Science Foundation Ireland and by the University College Dublin Seed-Funding program, and was an opportunity for the Irish Drug Delivery Network to invite selected internationally-recognized scientists from across Europe onto a program, together with some of its own principal investigators. The meeting was co-promoted by the UK and Ireland Controlled Release Society. Topics included fluorescent dyes for stability testing of proteins, engineering of nano-containers, peptide-polymer conjugates, designing novel biomaterials, oral liquid-emulsion drug delivery systems, barrier modulation for drug delivery to the eye using siRNA, cell-specific targeting in the lungs, hot-melt extrusion and modified cyclodextrins for delivery of siRNA. The conference was attended by 85 researchers and the Irish Drug Delivery Network co-chairs were Caitriona O'Driscoll (University College Cork) and David Brayden (University College Dublin). PMID:22833963

Brayden, David J; Armstrong, Graham; O'Driscoll, Caitriona M

2010-10-01

202

An oral-controlled release drug delivery system for liquid and semisolid drug formulations.  

PubMed

A novel oral drug delivery system for the controlled release of liquid drugs, drug solutions, and semisolid drug preparations is presented that is utilizing the constant vapor pressure of liquefied gas. The system is equipped with a capillary as an element determining the drug delivery rate and contains a liquefied propellant with a suitable boiling point below human body temperature. In the dissolution studies, polyacrylate gels of different viscosities containing paracetamol as model drug were used. Zero-order release kinetics was obtained. The release rates were dependent on the gel viscosity. Besides, by gel viscosity, the drug release rates could also be modified by changing the propellant type and the capillary parameters such as length or diameter. Accordingly, the new system enables a wide range of drug delivery kinetics which can be modified in a case-by-case basis in order to match the desired drug delivery characteristics. PMID:21918919

Haznar-Garbacz, Dorota; Garbacz, Grzegorz; Eisenächer, Friederike; Klein, Sandra; Weitschies, Werner

2011-12-01

203

Poly(ethylene glycol) Amphiphilic Copolymer for Anticancer Drugs Delivery.  

PubMed

Poly(ethylene glycol) is a water-soluble polymer. Due to its high safety and biocompatibility, it has been widely used to prepare amphiphilic copolymers for drug delivery. These copolymers can enhance water-solubility of hydrophobic drugs, improve their pharmacokinetic parameters and control their release from corresponding nanocarriers formed by its self-assembly. Anticancer drugs have some shortcoming such as lower water-solubility, bad targeting and some serious side-effects, which limit their applications and are dangerous to patients. So encapsulation of anticancer drugs into nanocarriers originated from its copolymeric derivates can improve their absorption, distribution, metabolism and excretion with better release properties and activities against cancer cells, increase their therapeutic effects, and realize their passive or active target delivery through structure modification. Recent research development of its drug delivery systems for anticancer drugs will be discussed. PMID:25420636

Feng, Runliang; Zhu, Wenxia; Teng, Fangfang; Liu, Na; Yang, Fengying; Meng, Ning; Song, Zhimei

2014-11-23

204

A fully implantable intracochlear drug delivery device : development and characterization  

E-print Network

In a collaborative effort with the Massachusetts Eye and Ear Infirmary, Draper Laboratory is developing an implantable microfluidic drug delivery system for long-term treatment of inner ear disorders and prevention of ...

Swan, Erin Eileen Leary, 1976-

2009-01-01

205

Microcapsule drug delivery device for treatment of glioblastoma multiforme  

E-print Network

Controlled-release drug delivery systems are capable of treating debilitating diseases, including cancer. Brain cancer, in particular glioblastoma multiforme (GBM), is an extremely invasive cancer with a dismal prognosis. ...

Scott, Alexander Wesley

2010-01-01

206

Photoswitchable Nanoparticles for Triggered Tissue Penetration and Drug Delivery  

E-print Network

We report a novel nanoparticulate drug delivery system that undergoes reversible volume change from 150 to 40 nm upon phototriggering with UV light. The volume change of these monodisperse nanoparticles comprising spiropyran, ...

Tong, Rong

207

Noninvasive quantification of drug delivery from an implantable MEMS device  

E-print Network

(cont.) sensors in vivo in real time and corroborated by scintillation of urine samples. The goal of monitoring drug delivery from an implant in vivo, in real time and without disturbing the tissue environment, was ...

Johnson, Audrey M., 1976-

2005-01-01

208

Near Infrared-Sensitive Nanoparticles for Targeted Drug Delivery  

E-print Network

The invasive nature and undesirable side-effects related to conventional cancer therapy, such as surgery and chemotherapy, have led to the development of novel drug delivery systems (DDS). A minimally invasive DDS using ...

Tan, Mei Chee

209

Mechanical loading impacts intramuscular drug transport : impact on local drug delivery  

E-print Network

Controlled-release drug-delivery systems enable efficient and defined administration of therapeutic agents to target tissues. However, ultimate drug distribution and pharmacologic effect are determined by target tissue ...

Wu, Peter I-Kung

2008-01-01

210

Mixed micelle formation with hydrophobic and hydrophilic Pluronic block copolymers: implications for controlled and targeted drug delivery.  

PubMed

Pluronic block copolymers offer affluent phase behavioral characteristics and are extensively investigated for drug delivery applications. Hydrophobic Pluronics produce larger aggregates whereas hydrophilic Pluronics often generate small-sized micelles in aqueous milieu. To overcome the limitations and combine the advantages of different kinds of Pluronics the mixing of such two types of Pluronics is studied here, especially for hydrophobic Pluronic L81 and relatively hydrophilic Pluronic P123. Critical micelle concentration (CMC) of the developed binary mixtures was 0.032 mg/ml as evidenced from pyrene fluorescence spectroscopy and is located in between that of the individual Pluronics. Dynamic light scattering (DLS) showed very small particle sizes (?20 nm) and low polydispersity indices for most of the mixed micelles. Transmission electron microscopy (TEM) demonstrated spherical shape of micelles. Based upon the ratio of hydrophobic and hydrophilic Pluronics, dispersions of varied stability were obtained. With 0.1/1.0 wt.% and 0.5/3.0 wt.% of Pluronic L81/P123, stable dispersions were obtained. Stability was assessed from turbidity measurement, size analysis and clarity of dispersion on standing. Micelles were also found to be stable in bovine serum albumin (BSA) solution. Mixed micelles showed fairly high entrapment efficiency, loading capacity and sustained release profile for aceclofenac (Acl), a model hydrophobe. Presence of salt lowered Acl solubilization in micelles. Thermodynamic parameters for Acl solubilization in mixed micelles revealed high partition coefficient values and spontaneity of drug solubilization. Thus, the developed novel mixed micelles hold promise in controlled and targeted drug delivery owing to their very small size, high entrapment efficiency and stability. PMID:21862296

Kulthe, S S; Inamdar, N N; Choudhari, Y M; Shirolikar, S M; Borde, L C; Mourya, V K

2011-12-01

211

Micelles and Nanoparticles for Ultrasonic Drug and Gene Delivery  

PubMed Central

Drug delivery research employing micelles and nanoparticles has expanded in recent years. Of particular interest is the use of these nanovehicles that deliver high concentrations of cytotoxic drugs to diseased tissues selectively, thus reducing the agent’s side effects on the rest of the body. Ultrasound, traditionally used in diagnostic medicine, is finding a place in drug delivery in connection with these nanoparticles. In addition to their non-invasive nature and the fact that they can be focused on targeted tissues, acoustic waves have been credited with releasing pharmacological agents from nanocarriers, as well as rendering cell membranes more permeable. In this article, we summarize new technologies that combine the use of nanoparticles with acoustic power both in drug and gene delivery. Ultrasonic drug delivery from micelles usually employs polyether block copolymers, and has been found effective in vivo for treating tumors. Ultrasound releases drug from micelles, most probably via shear stress and shock waves from collapse of cavitation bubbles. Liquid emulsions and solid nanoparticles are used with ultrasound to deliver genes in vitro and in vivo. The small packaging allows nanoparticles to extravasate into tumor tissues. Ultrasonic drug and gene delivery from nano-carriers has tremendous potential because of the wide variety of drugs and genes that could be delivered to targeted tissues by fairly non-invasive means. PMID:18486269

Husseini, Ghaleb A.; Pitt, William G.

2008-01-01

212

Usefulness verification of biocompatible microneedle patch for transdermal drug delivery  

Microsoft Academic Search

The key issues in the development of a microneedle patch as a tool for transdermal drug delivery are safety and delivery performance in addition to economical production. In this paper, a novel fabrication method for an inexpensive microneedle patch made of biocompatible polymer is reported, along with verifications for the fabricated microneedle patch. For microneedle patch fabrication, we combined the

Chun Yan Jin; Man Hee Han; S. S. Lee; Yo Han Choi

2009-01-01

213

Novel Approaches for Retinal Drug and Gene Delivery.  

PubMed

The ARVO 2014 minisymposium on "Novel Approaches for Retinal Drug and Gene Delivery" was held on May 6, 2014 in Orlando, FL. The main intent of the symposium was to review recent advances in retinal drug and gene delivery with specific emphasis on novel approaches that address current limitations and have the potential to translate into clinical practice. The symposium was sponsored by Translational Vision Science and Technology. PMID:25346872

Kim, Stephen J

2014-09-01

214

Application of plant viruses as nano drug delivery systems.  

PubMed

Nano-sized drug delivery systems based on virus-derived platforms have promising delivery and targeting efficiencies. To date, much of our understanding of these systems is obtained from studies of animal viruses. Application of plant viruses for drug delivery is in the nascent stage, but it is becoming apparent that plant viral particles can be engineered to possess novel properties to meet the unique requirements of targeted drug delivery. Chemical functionalization of a plant viral particle surface can impart stealth properties to prolong in vivo circulation half-life and/or targeting capability to direct drug delivery to diseased tissues. The amino acid sequence of the viral coat protein can be genetically manipulated to yield protein cages of specific chemistry and morphology, while the conformation of the protein cage can be directed, via the external environment, to disassemble, then reassemble in vitro to exchange native viral genomic material with exogenous cargo. The purpose of this commentary is to evaluate current literature to assess the potential of nano-scale plant-virus-based drug delivery systems for the targeted delivery of chemotherapeutic agents. PMID:20811934

Ren, Yupeng; Wong, Sek Man; Lim, Lee Yong

2010-11-01

215

Nasal Drug Delivery in Traditional Persian Medicine  

PubMed Central

Background Over one hundred different pharmaceutical dosage forms have been recorded in literatures of Traditional Persian Medicine among which nasal forms are considerable. Objectives This study designed to derive the most often applied nasal dosage forms together with those brief clinical administrations. Materials and Methods In the current study remaining pharmaceutical manuscripts of Persia during 9th to 18th century AD have been studied and different dosage forms related to nasal application of herbal medicines and their therapeutic effects were derived. Results By searching through pharmaceutical manuscripts of medieval Persia, different nasal dosage forms involving eleven types related to three main groups are found. These types could be derived from powder, solution or liquid and gaseous forms. Gaseous form were classified into fumigation (Bakhoor), vapor bath (Enkebab), inhalation (Lakhlakheh), aroma agents (Ghalieh) and olfaction or smell (Shomoom). Nasal solutions were as drops (Ghatoor), nasal snuffing drops (Saoot) and liquid snuff formulations (Noshoogh). Powders were as nasal insufflation or snorting agents (Nofookh) and errhine or sternutator medicine (Otoos). Nasal forms were not applied only for local purposes. Rather systemic disorders and specially CNS complications were said to be a target for these dosage forms. Discussion While this novel type of drug delivery is known as a suitable substitute for oral and parenteral administration, it was well accepted and extensively mentioned in Persian medical and pharmaceutical manuscripts and other traditional systems of medicine as well. Accordingly, medieval pharmaceutical standpoints on nasal dosage forms could still be an interesting subject of study. Therefore, the current work can briefly show the pharmaceutical knowledge on nasal formulations in medieval Persia and clarify a part of history of traditional Persian pharmacy. PMID:24624204

Zarshenas, Mohammad Mehdi; Zargaran, Arman; Müller, Johannes; Mohagheghzadeh, Abdolali

2013-01-01

216

Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety  

PubMed Central

Many promising therapeutic agents are limited by their inability to reach the systemic circulation, due to the excellent barrier properties of biological membranes, such as the stratum corneum (SC) of the skin or the sclera/cornea of the eye and others. The outermost layer of the skin, the SC, is the principal barrier to topically-applied medications. The intact SC thus provides the main barrier to exogenous substances, including drugs. Only drugs with very specific physicochemical properties (molecular weight < 500 Da, adequate lipophilicity, and low melting point) can be successfully administered transdermally. Transdermal delivery of hydrophilic drugs and macromolecular agents of interest, including peptides, DNA, and small interfering RNA is problematic. Therefore, facilitation of drug penetration through the SC may involve by-pass or reversible disruption of SC molecular architecture. Microneedles (MNs), when used to puncture skin, will by-pass the SC and create transient aqueous transport pathways of micron dimensions and enhance the transdermal permeability. These micropores are orders of magnitude larger than molecular dimensions, and, therefore, should readily permit the transport of hydrophilic macromolecules. Various strategies have been employed by many research groups and pharmaceutical companies worldwide, for the fabrication of MNs. This review details various types of MNs, fabrication methods and, importantly, investigations of clinical safety of MN. PMID:20297904

Donnelly, Ryan F.; Raj Singh, Thakur Raghu; Woolfson, A. David

2010-01-01

217

Stimuli sensitive hydrogels for ophthalmic drug delivery: A review  

PubMed Central

Amongst the various routes of drug delivery, the field of ocular drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist for past 10-20 years. As an isolated organ, eye is very difficult to study from a drug delivery point of view. Despite this limitation, improvements have been made with the objective of maintaining the drug in the biophase for an extended period. A major problem in ocular therapeutics is the attainment of an optimal drug concentration at the site of action. To achieve effective ophthalmic therapy, an adequate amount of active ingredient must be delivered and maintained within the eye. The most frequently used dosage forms, i.e., eye solution, eye ointments, eye gels, and eye suspensions are compromised in their effectiveness by several limitations leading to poor ocular bioavailability. Ophthalmic use of viscosity-enhancing agents, penetration enhancers, cyclodextrins, prodrug approaches, and ocular inserts, and the ready existing drug carrier systems along with their application to ophthalmic drug delivery are common to improve ocular bioavailability. Amongst these hydrogel (stimuli sensitive) systems are important, which undergo reversible volume and/or sol-gel phase transitions in response to physiological (temperature, pH and present of ions in organism fluids, enzyme substrate) or other external (electric current, light) stimuli. They help to increase in precorneal residence time of drug to a sufficient extent that an ocularly delivered drug can exhibit its maximum biological action. The concept of this innovative ophthalmic delivery approach is to decrease the systemic side effects and to create a more pronounced effect with lower doses of the drug. The present article describes the advantages and use stimuli sensitive of hydrogel systems in ophthalmic drug delivery. PMID:23119233

Kushwaha, Swatantra KS; Saxena, Prachi; Rai, AK

2012-01-01

218

Planar bioadhesive microdevices: a new technology for oral drug delivery  

PubMed Central

The oral route is the most convenient and least expensive route of drug administration. Yet, it is accompanied by many physiological barriers to drug uptake including low stomach pH, intestinal enzymes and transporters, mucosal barriers, and high intestinal fluid shear. While many drug delivery systems have been developed for oral drug administration, the physiological components of the gastro intestinal tract remain formidable barriers to drug uptake. Recently, microfabrication techniques have been applied to create micron-scale devices for oral drug delivery with a high degree of control over microdevice size, shape, chemical composition, drug release profile, and targeting ability. With precise control over device properties, microdevices can be fabricated with characteristics that provide increased adhesion for prolonged drug exposure, unidirectional release which serves to avoid luminal drug loss and enhance drug permeation, and protection of a drug payload from the harsh environment of the intestinal tract. Here we review the recent developments in microdevice technology and discuss the potential of these devices to overcome unsolved challenges in oral drug delivery. PMID:25219863

Fox, Cade B.; Chirra, Hariharasudhan D.; Desai, Tejal A.

2014-01-01

219

Critical Assessment of Implantable Drug Delivery Devices in Glaucoma Management  

PubMed Central

Glaucoma is a group of heterogeneous disorders involving progressive optic neuropathy that can culminate into visual impairment and irreversible blindness. Effective therapeutic interventions must address underlying vulnerability of retinal ganglion cells (RGCs) to degeneration in conjunction with correcting other associated risk factors (such as elevated intraocular pressure). However, realization of therapeutic outcomes is heavily dependent on suitable delivery system that can overcome myriads of anatomical and physiological barriers to intraocular drug delivery. Development of clinically viable sustained release systems in glaucoma is a widely recognized unmet need. In this regard, implantable delivery systems may relieve the burden of chronic drug administration while potentially ensuring high intraocular drug bioavailability. Presently there are no FDA-approved implantable drug delivery devices for glaucoma even though there are several ongoing clinical studies. The paper critically assessed the prospects of polymeric implantable delivery systems in glaucoma while identifying factors that can dictate (a) patient tolerability and acceptance, (b) drug stability and drug release profiles, (c) therapeutic efficacy, and (d) toxicity and biocompatibility. The information gathered could be useful in future research and development efforts on implantable delivery systems in glaucoma. PMID:24066234

Manickavasagam, Dharani; Oyewumi, Moses O.

2013-01-01

220

Molecularly imprinted polymers as the future drug delivery devices.  

PubMed

In recent years, the investigations of new drug delivery systems have been directed on the development of some "intelligent" drug delivery devices that are able to directly respond to the patient's individual needs. New drug delivery systems should maximize the efficiency of administrated therapeutic agents and improve the patient's quality of life. Introduction of the new drug delivery devices is an important scientific goal, which could be achieved by combining new technologies and intelligent biomaterials. Molecular imprinting technology has a high potential for the preparation of optimized drug delivery forms. Here, molecularly imprinted polymers (MIPs) are promising new materials for such purposes, but their application in this field is nowadays at a developing stage. In this review, the principles of molecular imprinting and the recognition-release mechanisms of polymeric matrices are discussed. The potential application of molecularly imprinted materials as the future drug delivery systems with various administering routes (transdermal, ocular or oral) are presented, and some future prospects for the imprinted polymers are outlined. PMID:23923384

Luli?ski, Piotr

2013-01-01

221

Ultrasonic gene and drug delivery using eLiposomes.  

PubMed

eLiposomes are liposomes encapsulating emulsions and therapeutics for targeted delivery. By applying ultrasound to eLiposomes, emulsion droplets can transform from liquid to gas and rupture the lipid bilayer of the eLiposome to release a drug or plasmid. In this study, perfluoropentane (PFC5) emulsions were encapsulated inside folated eLiposomes carrying a model drug (calcein) or a model GFP plasmid to examine the effects of a folate ligand, PFC5 emulsion and various ultrasonic acoustic parameters in drug delivery and gene transfection into HeLa cells. Confocal microscopy was used to quantify drug delivery and the level of plasmid transfection into HeLa cells. The results showed that drug delivery or transfection was minimal without incorporation of internal PFC5 emulsions and folate ligand on the eLiposome surface. It was also shown that application of ultrasound greatly enhanced the drug delivery and plasmid transfection. Delivery of these therapeutics appears to be to the cytosol, indicating that the expansion of the emulsion droplets disrupted both the eLiposomes and the endosomes. PMID:23352908

Javadi, Marjan; Pitt, William G; Tracy, Christopher M; Barrow, Jeffery R; Willardson, Barry M; Hartley, Jonathan M; Tsosie, Naakaii H

2013-04-10

222

3-dimensional (3D) fabricated polymer based drug delivery systems.  

PubMed

Drug delivery from 3-dimensional (3D) structures is a rapidly growing area of research. It is essential to achieve structures wherein drug stability is ensured, the drug loading capacity is appropriate and the desired controlled release profile can be attained. Attention must also be paid to the development of appropriate fabrication machinery that allows 3D drug delivery systems (DDS) to be produced in a simple, reliable and reproducible manner. The range of fabrication methods currently being used to form 3D DDSs include electrospinning (solution and melt), wet-spinning and printing (3-dimensional). The use of these techniques enables production of DDSs from the macro-scale down to the nano-scale. This article reviews progress in these fabrication techniques to form DDSs that possess desirable drug delivery kinetics for a wide range of applications. PMID:25020039

Moulton, Simon E; Wallace, Gordon G

2014-11-10

223

A Review on Composite Liposomal Technologies for Specialized Drug Delivery  

PubMed Central

The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. Two approaches for overcoming the factors related to the suboptimal efficacy of liposomes in drug delivery have been suggested. The first entails modifying the liposome surface with functional moieties, while the second involves integration of pre-encapsulated drug-loaded liposomes within depot polymeric scaffolds. This attempts to provide ingenious solutions to the limitations of conventional liposomes such as short plasma half-lives, toxicity, stability, and poor control of drug release over prolonged periods. This review delineates the key advances in composite technologies that merge the concepts of depot polymeric scaffolds with liposome technology to overcome the limitations of conventional liposomes for pharmaceutical applications. PMID:21490759

Mufamadi, Maluta S.; Pillay, Viness; Choonara, Yahya E.; Du Toit, Lisa C.; Modi, Girish; Naidoo, Dinesh; Ndesendo, Valence M. K.

2011-01-01

224

Nanostructured materials for applications in drug delivery and tissue engineering*  

PubMed Central

Research in the areas of drug delivery and tissue engineering has witnessed tremendous progress in recent years due to their unlimited potential to improve human health. Meanwhile, the development of nanotechnology provides opportunities to characterize, manipulate and organize matter systematically at the nanometer scale. Biomaterials with nano-scale organizations have been used as controlled release reservoirs for drug delivery and artificial matrices for tissue engineering. Drug-delivery systems can be synthesized with controlled composition, shape, size and morphology. Their surface properties can be manipulated to increase solubility, immunocompatibility and cellular uptake. The limitations of current drug delivery systems include suboptimal bioavailability, limited effective targeting and potential cytotoxicity. Promising and versatile nano-scale drug-delivery systems include nanoparticles, nanocapsules, nanotubes, nanogels and dendrimers. They can be used to deliver both small-molecule drugs and various classes of biomacromolecules, such as peptides, proteins, plasmid DNA and synthetic oligodeoxynucleotides. Whereas traditional tissue-engineering scaffolds were based on hydrolytically degradable macroporous materials, current approaches emphasize the control over cell behaviors and tissue formation by nano-scale topography that closely mimics the natural extracellular matrix (ECM). The understanding that the natural ECM is a multifunctional nanocomposite motivated researchers to develop nanofibrous scaffolds through electrospinning or self-assembly. Nanocomposites containing nanocrystals have been shown to elicit active bone growth. Drug delivery and tissue engineering are closely related fields. In fact, tissue engineering can be viewed as a special case of drug delivery where the goal is to accomplish controlled delivery of mammalian cells. Controlled release of therapeutic factors in turn will enhance the efficacy of tissue engineering. From a materials point of view, both the drug-delivery vehicles and tissue-engineering scaffolds need to be biocompatible and biodegradable. The biological functions of encapsulated drugs and cells can be dramatically enhanced by designing biomaterials with controlled organizations at the nanometer scale. This review summarizes the most recent development in utilizing nanostructured materials for applications in drug delivery and tissue engineering. PMID:17471764

GOLDBERG, MICHAEL; LANGER, ROBERT; JIA, XINQIAO

2010-01-01

225

Polymeric nanofibers: targeted gastro-retentive drug delivery systems.  

PubMed

Abstract Background: Conventional oral dosage forms exhibit poor/low bioavailability due to incomplete release of drug and short residence time at the absorption site. Gastro-retentive drug delivery system (GRDDS) is particularly used to improve bioavailability of the drugs, which have narrow absorption window down in the levels of gastrointestinal tract and also to treat local disorders. Purpose: The purpose of this review is to describe the utility of the nanofibers as gastro-retentive dosage form. From last few decades, formulation scientists have put extensive efforts to develop suitable gastro-retentive drug delivery system, which is appropriate for commercialization. Current approaches used for preparation of gastro-retentive drug delivery system offers limited functional features to control the floating behavior. Recently, an extensive research has been developed to improve the gastric residence time by using nanofibers, which ultimately leads to the increased bioavailability of the drug. Multiple functional features and unique properties of nanofibers improve its gastro retention. Conclusion: Nanofiber system provides stomach-specific drug release for longer duration; moreover, increased local action of the drug due to prolonged contact time with the gastric mucosa. Thus, the nanofiber system promises to be the potential approach for gastric retention drug delivery system. PMID:25268275

Malik, Rafi; Garg, Tarun; Goyal, Amit K; Rath, Goutam

2014-09-30

226

pH-Responsive Drug-Delivery Systems.  

PubMed

In many biomedical applications, drugs need to be delivered in response to the pH value in the body. In fact, it is desirable if the drugs can be administered in a controlled manner that precisely matches physiological needs at targeted sites and at predetermined release rates for predefined periods of time. Different organs, tissues, and cellular compartments have different pH values, which makes the pH value a suitable stimulus for controlled drug release. pH-Responsive drug-delivery systems have attracted more and more interest as "smart" drug-delivery systems for overcoming the shortcomings of conventional drug formulations because they are able to deliver drugs in a controlled manner at a specific site and time, which results in high therapeutic efficacy. This focus review is not intended to offer a comprehensive review on the research devoted to pH-responsive drug-delivery systems; instead, it presents some recent progress obtained for pH-responsive drug-delivery systems and future perspectives. There are a large number of publications available on this topic, but only a selection of examples will be discussed. PMID:25303435

Zhu, Ying-Jie; Chen, Feng

2015-02-01

227

COMPUTATIONAL STUDIES OF CONTROLLED NANOPARTICLE AGGLOMERATIONS FOR MRI-GUIDED NANOROBOTIC DRUG-DELIVERY SYSTEMS  

E-print Network

COMPUTATIONAL STUDIES OF CONTROLLED NANOPARTICLE AGGLOMERATIONS FOR MRI-GUIDED NANOROBOTIC DRUG-DELIVERY in nanorobotic drug delivery. INTRODUCTION Nanorobotic drug delivery systems guided by Magnetic Resonance Imaging (MRI) scanners have been proposed for localized drug delivery in the human body. The expectation

Mavroidis, Constantinos

228

Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery  

NASA Astrophysics Data System (ADS)

A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations failed to reach. However, hypotonic formulations caused free drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. Minimally hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. We then describe an ex vivo method for characterizing particle transport on freshly excised mucosal tissues. By directly observing MPP transport on vaginal, gastrointestinal, and respiratory tissue, we were able to determine an innate difference in mucus mesh size at different anatomical locations. In addition, we were able to optimize particle size for gastrointestinal delivery in mice. As described here, there are numerous barriers to effective drug delivery in the gastrointestinal tract, including the mucus barrier. We go on to demonstrate that MPP can improve delivery in the gastrointestinal tract, both by rectal and oral administration. Finally, we describe the use of MPP for improving vaginal drug delivery. Incomplete drug coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides for preventing sexually transmitted infections. We show that MPP provide uniform distribution over the vaginal epithelium, whereas CP are aggregated by mouse vaginal mucus, leading to poor distribution. By penetrating into the deepest mucus layers in the rugae, more MPP were retained in the vaginal tract compared to CP. After 24 h, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPP. We then demonstrate that when administered 30 min prior to inoculum, anti-HSV-2 MPP protected

Ensign-Hodges, Laura

229

An Implantable MEMS Drug Delivery Device for Rapid Delivery in Ambulatory Emergency Care  

E-print Network

We introduce the first implantable drug delivery system based on MEMS (Micro-Electro-Mechanical-Systems) technology specifically designed as a platform for treatment in ambulatory emergency care. The device is named ...

Elman, Noel

230

Microsystems Technologies for Drug Delivery to the Inner Ear  

PubMed Central

The inner ear represents one of the most technologically challenging targets for local drug delivery, but its clinical significance is rapidly increasing. The prevalence of sensorineural hearing loss and other auditory diseases, along with balance disorders and tinnitus, has spurred broad efforts to develop therapeutic compounds and regenerative approaches to treat these conditions, necessitating advances in systems capable of targeted and sustained drug delivery. The delicate nature of hearing structures combined with the relative inaccessibility of the cochlea by means of conventional delivery routes together necessitate significant advancements in both the precision and miniaturization of delivery systems, and the nature of the molecular and cellular targets for these therapies suggests that multiple compounds may need to be delivered in a time-sequenced fashion over an extended duration. Here we address the various approaches being developed for inner ear drug delivery, including micropump-based devices, reciprocating systems, and cochlear prosthesis-mediated delivery, concluding with an analysis of emerging challenges and opportunities for the first generation of technologies suitable for human clinical use. These developments represent exciting advances that have the potential to repair and regenerate hearing structures in millions of patients for whom no currently available medical treatments exist, a situation that requires them to function with electronic hearing augmentation devices or to live with severely impaired auditory function. These advances also have the potential for broader clinical applications that share similar requirements and challenges with the inner ear, such as drug delivery to the central nervous system. PMID:22386561

Leary Pararas, Erin E.; Borkholder, David A.; Borenstein, Jeffrey T.

2012-01-01

231

An Intravaginal Ring for the Simultaneous Delivery of Multiple Drugs  

PubMed Central

Intravaginal delivery of microbicide combinations is a promising approach for the prevention of sexually transmitted infections, but requires a method of providing simultaneous, independent release of multiple agents into the vaginal compartment. A novel intravaginal ring (IVR) platform has been developed for simultaneous delivery of the reverse-transcriptase inhibitor tenofovir (TFV) and the guanosine analogue antiviral acyclovir (ACV) with independent control of release rate for each drug. The IVR is based on a pod design, with up to 10 individual polymer-coated drug cores embedded in the ring releasing through preformed delivery channels. The release rate from each pod is controlled independently of the others by the drug properties, polymer coating, and size and number of delivery channels. Pseudo-zero-order in vitro release of TFV (144 ± 10 µg day) and ACV (120 ± 19 µg day?1) from an IVR containing both drugs was sustained for 28 days. The mechanical properties of the pod IVR were evaluated and compared with the commercially available Estring® (Pfizer, NY, NY). The pod-IVR design enables the vaginal delivery of multiple microbicides with differing physicochemical properties, and is an attractive approach for the sustained intravaginal delivery of relatively hydrophilic drugs that are difficult to deliver using conventional matrix IVR technology. PMID:22619076

Baum, Marc M.; Butkyavichene, Irina; Gilman, Joshua; Kennedy, Sean; Kopin, Etana; Malone, Amanda M.; Nguyen, Cali; Smith, Thomas J.; Friend, David R.; Clark, Meredith R.; Moss, John A.

2013-01-01

232

Micro-scale Devices for Transdermal Drug Delivery  

PubMed Central

Skin makes an excellent site for drug and vaccine delivery due to easy accessibility, immuno-surveillance functions, avoidance of macromolecular degradation in the gastrointestinal tract and possibility of self-administration. However, macromolecular drug delivery across the skin is primarily accomplished using hypodermic needles, which have several disadvantages including accidental needle-sticks, pain and needle phobia. These limitations have led to extensive research and development of alternative methods for drug and vaccine delivery across the skin. This review focuses on the recent trends and developments in this field of micro-scale devices for transdermal macromolecular delivery. These include liquid jet injectors, powder injectors, microneedles and thermal microablation. The historical perspective, mechanisms of action, important design parameters, applications and challenges are discussed for each method. PMID:18805472

Arora, Anubhav; Prausnitz, Mark; Mitragotri, Samir

2009-01-01

233

Nanotechnology: A Focus on Nanoparticles as a Drug Delivery System  

Microsoft Academic Search

This review will provide an in-depth discussion on the previous development of nanoparticle-based drug delivery systems (DDS) and discuss original research data that includes the therapeutic enhancement of antiretroviral therapy. The use of nanoparticle DDS will allow practitioners to use drugs to target specific areas of the body. In the treatment of malignancies, the use of nanoparticles as a DDS

Jeffrey D. Kingsley; Huanyu Dou; Justin Morehead; Barrett Rabinow; Howard E. Gendelman; Christopher J. Destache

2006-01-01

234

Cooperative Nanoparticles for Tumor Detection and Photothermally Triggered Drug Delivery  

E-print Network

are commonly employed in a wide range of cancer treatments. In particular, hyperthermia can increase and vessel permeability.[7,8] Hyperthermia can also enhance drug toxicity in cancer cells that are otherwise functions, such as magnetic resonance imaging, magnetic drug delivery and hyperthermia,[4] but the loading

Bhatia, Sangeeta

235

Nano-engineering block copolymer aggregates for drug delivery  

Microsoft Academic Search

This review describes the properties of block copolymer micelles which influence their efficiency as drug delivery vehicles for hydrophobic drugs. The key performance related properties we discuss are loading capacity, release kinetics, circulation time, biodistribution, size, size distribution and stability. Each of the properties is discussed in detail with specific attention given to the way in which they may be

Christine Allen; Dusica Maysinger; Adi Eisenberg

1999-01-01

236

Porous Carriers for Controlled/Modulated Drug Delivery  

PubMed Central

Considerable research efforts have been directed in recent years towards the development of porous carriers as controlled drug delivery matrices because of possessing several features such as stable uniform porous structure, high surface area, tunable pore size and well-defined surface properties. Owing to wide range of useful properties porous carriers have been used in pharmaceuticals for many purposes including development of floating drug delivery systems, sustained drug delivery systems. Various types of pores like open, closed, transport and blind pores in the porous solid allow them to adsorb drugs and release them in a more reproducible and predictable manner. Pharmaceutically exploited porous adsorbents includes, silica (mesoporous), ethylene vinyl acetate (macroporous), polypropylene foam powder (microporous), titanium dioxide (nanoporous). When porous polymeric drug delivery system is placed in contact with appropriate dissolution medium, release of drug to medium must be preceded by the drug dissolution in the water filled pores or from surface and by diffusion through the water filled channels. The porous carriers are used to improve the oral bioavailability of poorly water soluble drugs, to increase the dissolution of relatively insoluble powders and conversion of crystalline state to amorphous state. PMID:20376211

Ahuja, G.; Pathak, K.

2009-01-01

237

Mechanism of laser-induced drug delivery in tumors  

Microsoft Academic Search

Penetration of anti-cancer drugs (especially macromolecular agents) from blood in tumor cells is limited due to the presence of physiological barriers: tumor capillary wall, slow diffusion in the interstitium, and cancer cell membrane. Interaction of exogenous nano- or microparticles with laser or ultrasonic radiation may enhance drug delivery in tumor cells due to laser- or ultrasound-induced cavitation. Our previous studies

Rinat O. Esenaliev; Irina V. Larina; Kirill V. Larin; Massoud Motamedi; B. M. Evers

2000-01-01

238

Aptamer-Gated Nanoparticles for Smart Drug Delivery  

PubMed Central

Aptamers are functional nucleic acid sequences which can bind specific targets. An artificial combinatorial methodology can identify aptamer sequences for any target molecule, from ions to whole cells. Drug delivery systems seek to increase efficacy and reduce side-effects by concentrating the therapeutic agents at specific disease sites in the body. This is generally achieved by specific targeting of inactivated drug molecules. Aptamers which can bind to various cancer cell types selectively and with high affinity have been exploited in a variety of drug delivery systems for therapeutic purposes. Recent progress in selection of cell-specific aptamers has provided new opportunities in targeted drug delivery. Especially functionalization of nanoparticles with such aptamers has drawn major attention in the biosensor and biomedical areas. Moreover, nucleic acids are recognized as an attractive building materials in nanomachines because of their unique molecular recognition properties and structural features. A active controlled delivery of drugs once targeted to a disease site is a major research challenge. Stimuli-responsive gating is one way of achieving controlled release of nanoparticle cargoes. Recent reports incorporate the structural properties of aptamers in controlled release systems of drug delivering nanoparticles. In this review, the strategies for using functional nucleic acids in creating smart drug delivery devices will be explained. The main focus will be on aptamer-incorporated nanoparticle systems for drug delivery purposes in order to assess the future potential of aptamers in the therapeutic area. Special emphasis will be given to the very recent progress in controlled drug release based on molecular gating achieved with aptamers.

Ozalp, Veli Cengiz; Eyidogan, Fusun; Oktem, Huseyin Avni

2011-01-01

239

Nanomedicine strategies for drug delivery to the ear.  

PubMed

The highly compartmentalized anatomy of the ear aggravates drug delivery, which is used to combat hearing-related diseases. Novel nanosized drug vehicles are thought to overcome the limitations of classic approaches. In this article, we summarize the nanotechnology-based efforts involving nano-objects, such as liposomes, polymersomes, lipidic nanocapsules and poly(lactic-co-glycolic acid) nanoparticles, as well as nanocoatings of implants to provide an efficient means for drug transfer in the ear. Modern strategies do not only enhance drug delivery efficiency, in the inner ear these vector systems also aim for specific uptake into hair cells and spiral ganglion neurons. These novel peptide-mediated strategies for specific delivery are reviewed in this article. Finally, the biosafety of these vector systems is still an outstanding issue, since long-term application to the ear has not yet been assessed. PMID:23837855

Pritz, Christian Oliver; Dudás, József; Rask-Andersen, Helge; Schrott-Fischer, Anneliese; Glueckert, Rudolf

2013-07-01

240

Tissue Bioeffects during Ultrasound-mediated Drug Delivery  

NASA Astrophysics Data System (ADS)

Ultrasound has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. Vascular effects can be mediated by mechanical oscillations of circulating microbubbles, or ultrasound contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi, or direct drugs to optimal locations for delivery. These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery. This dissertation addresses a fundamental hypothesis in biomedical ultrasound: ultrasound-mediated drug delivery is capable of increasing the penetration of drugs across different physiologic barriers within the cardiovascular system, such as the vascular endothelium, blood clots, and smooth muscle cells.

Sutton, Jonathan

241

Pulsatile Drug Delivery System Based on Electrohydrodynamic Method  

E-print Network

Electrohydrodynamic (EHD) generation, a commonly used method in BioMEMS, plays a significant role in the pulsatile drug delivery system for a decade. In this paper, an EHD based drug delivery system is well designed, which can be used to generate a single drug droplet as small as 2.83 nL in 8.5 ms with a total device of 2\\times2\\times3 mm^3, and an external supplied voltage of 1500 V. Theoretically, we derive the expressions for the size and the formation time of a droplet generated by EHD method, while taking into account the drug supply rate, properties of liquid, gap between two electrodes, nozzle size, and charged droplet neutralization. This work proves a repeatable, stable and controllable droplet generation and delivery system based on EHD method experimentally as well as theoretically.

Zheng, Yi; Hu, Junqiang; Gao, Wenle

2012-01-01

242

Basics and recent advances in peptide and protein drug delivery.  

PubMed

While the peptide and protein therapeutic market has developed significantly in the past decades, delivery has limited their use. Although oral delivery is preferred, most are currently delivered intravenously or subcutaneously due to degradation and limited absorption in the gastrointestinal tract. Therefore, absorption enhancers, enzyme inhibitors, carrier systems and stability enhancers are being studied to facilitate oral peptide delivery. Additionally, transdermal peptide delivery avoids the issues of the gastrointestinal tract, but also faces absorption limitations. Due to proteases, opsonization and agglutination, free peptides are not systemically stable without modifications. This review discusses oral and transdermal peptide drug delivery, focusing on barriers and solutions to absorption and stability issues. Methods to increase systemic stability and site-specific delivery are also discussed. PMID:24228993

Bruno, Benjamin J; Miller, Geoffrey D; Lim, Carol S

2013-11-01

243

Ultrasound-enhanced drug delivery for efficient cancer therapy  

Microsoft Academic Search

Poor penetration of anti-cancer drugs through tumor vasculature and cancer cell membrane as well as slow diffusion of the drugs in the interstitium limit efficacy of cancer chemo- and biotherapy. Recently we proposed to use ultrasound-induced cavitation (formation, growth, and collapse of microbubbles) to enhance anti-cancer drug delivery through these barriers. Cavitation can be selectively induced in tumors by using

I. V. Larina; B. M. Evers; C. Bartels; T. V. Ashitkov; K. V. Larin; R. O. Esenaliev

2002-01-01

244

Development of novel drug delivery prototypes devices for targeted delivery drug therapy at the molecular level in aqueous media.  

PubMed

A novel approach in target specific molecular prototype drug delivery system concerns the attempt to employ radical affording substances (RAS) or radical quenching substances (RQS) as prodrugs able to produce irreversible damage on the desired target and therefore to stimulate cellular apoptosis. However, radical species generated can react quickly within the chemical environment prior to reaching its proper site of action. In this short communication, we report our investigations towards developing two alternative novel, simple, flexible and effective drug delivery systems that provide optimal dosage of drugs precisely where and when needed and therefore achieve and sustain a complex delivery profile. We have demonstrated the application of two effective molecular prototype delivery systems able to harness free radical reactivity within the laboratory where biological processes can be studied and controlled, leading to the prevention of disease and the development of new treatments for disease states mediated by free radicals. PMID:21843149

George, Roy; Oberhozer, Theunis Gerhardus; Perchyonok, Victoria Tamara

2011-09-01

245

Mathematical modeling of drug delivery from autocatalytically degradable PLGA microspheres --A review  

E-print Network

Review Mathematical modeling of drug delivery from autocatalytically degradable PLGA microspheres for controlled release drug delivery applications, and many models have been proposed to describe PLGA Accepted 18 October 2012 Available online 26 October 2012 Keywords: Modeling Controlled release drug

Braatz, Richard D.

246

Using DNA nanotechnology to produce a drug delivery system  

NASA Astrophysics Data System (ADS)

Drug delivery to cancer cells in chemotherapy is one of the most advanced research topics. The effectiveness of the current cancer treatment drugs is limited because they are not capable of distinguishing between cancer cells and normal cells so that they kill not only cancer cells but also normal ones. To overcome this disadvantage by profiting from the differences in physical and chemical properties between cancer and normal cells, nanoparticles (NPs) delivering a drug are designed in a specific manner such that they can distinguish the cancer cells from the normal ones and are targeted only to the cancer cells. Currently, there are various drug delivery systems with many advantages, but sharing some common disadvantages such as difficulty with controlling the size, low encapsulation capacity and low stability. With the development and success of DNA nanotechnology, DNA strands are used to create effective drug delivery NPs with precisely controlled size and structure, safety and high stability. This article presents our study on drug encapsulation in DNA nanostructure which loaded docetaxel and curcumin in a desire to create a new and effective drug delivery system with high biological compatibility. Invited talk at the 6th International Workshop on Advanced Materials Science and Nanotechnology, 30 October–2 November, 2012, Ha Long, Vietnam.

Huyen La, Thi; Thu Thuy Nguyen, Thi; Phuc Pham, Van; Huyen Nguyen, Thi Minh; Huan Le, Quang

2013-03-01

247

An emerging platform for drug delivery: aerogel based systems.  

PubMed

Over the past few decades, advances in "aerogel science" have provoked an increasing interest for these materials in pharmaceutical sciences for drug delivery applications. Because of their high surface areas, high porosities and open pore structures which can be tuned and controlled by manipulation of synthesis conditions, nanostructured aerogels represent a promising class of materials for delivery of various drugs as well as enzymes and proteins. Along with biocompatible inorganic aerogels and biodegradable organic aerogels, more complex systems such as surface functionalized aerogels, composite aerogels and layered aerogels have also been under development and possess huge potential. Emphasis is given to the details of the aerogel synthesis and drug loading methods as well as the influence of synthesis parameters and loading methods on the adsorption and release of the drugs. Owing to their ability to increase the bioavailability of low solubility drugs, to improve both their stability and their release kinetics, there are an increasing number of research articles concerning aerogels in different drug delivery applications. This review presents an up to date overview of the advances in all kinds of aerogel based drug delivery systems which are currently under investigation. PMID:24394377

Ulker, Zeynep; Erkey, Can

2014-03-10

248

Insights into drug delivery across the nail plate barrier.  

PubMed

Topical therapy is at the forefront in treating nail ailments (especially onychomycosis and nail psoriasis) due to its local effects, which circumvents systemic adverse events, improves patient compliance and reduces treatment cost. However, the success of topical therapy has been hindered due to poor penetration of topical therapeutics across densely keratinized nail plate barrier. For effective topical therapy across nail plate, ungual drug permeation must be enhanced. Present review is designed to provide an insight into prime aspects of transungual drug delivery viz. nail structure and physiology, various onychopathies, techniques of nail permeation enhancement and in vitro models for trans-nail drug permeation studies. Updated list of drug molecules studied across the nail plate and key commercial products have been furnished with sufficient depth. Patents pertinent to, and current clinical status of transungual drug delivery have also been comprehensively reviewed. This is the first systematic critique encompassing the detailed aspects of transungual drug delivery. In our opinion, transungual drug delivery is a promising avenue for researchers to develop novel formulations, augmenting pharmaceutical industries to commercialize the products for nail disorders. PMID:24964054

Saner, Manish V; Kulkarni, Abhijeet D; Pardeshi, Chandrakantsing V

2014-11-01

249

Development of a Microfluidics-Based Intracochlear Drug Delivery Device  

PubMed Central

Background Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration. Methods We have taken a microfluidics/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating inner-ear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the cochlea. Iterations of the device were tested in guinea pigs to determine the flow characteristics required for safe and effective delivery. For these tests, we used the glutamate receptor blocker DNQX, which alters auditory nerve responses but not cochlear distortion product otoacoustic emissions. Results We have demonstrated safe and effective delivery of agents into the scala tympani. Equilibration of the drug in the basal turn occurs rapidly (within tens of minutes) and is dependent on reciprocating flow parameters. Conclusion We have described a prototype system for the direct delivery of drugs to the inner ear that has the potential to be a fully implantable means for safe and effective treatment of hearing loss and other diseases. PMID:19923811

Sewell, William F.; Borenstein, Jeffrey T.; Chen, Zhiqiang; Fiering, Jason; Handzel, Ophir; Holmboe, Maria; Kim, Ernest S.; Kujawa, Sharon G.; McKenna, Michael J.; Mescher, Mark M.; Murphy, Brian; Leary Swan, Erin E.; Peppi, Marcello; Tao, Sarah

2009-01-01

250

EMERGING MICROTECHNOLOGIES FOR THE DEVELOPMENT OF ORAL DRUG DELIVERY DEVICES  

PubMed Central

The development of oral drug delivery platforms for administering therapeutics in a safe and effective manner across the gastrointestinal epithelium is of much importance. A variety of delivery systems such as enterically coated tablets, capsules, particles, and liposomes have been developed to improve oral bioavailability of drugs. However, orally administered drugs suffer from poor localization and therapeutic efficacy due to various physiological conditions such as low pH, and high shear intestinal fluid flow. Novel platforms combining controlled release, improved adhesion, tissue penetration, and selective intestinal targeting may overcome these issues and potentially diminish the toxicity and high frequency of administration associated with conventional oral delivery. Microfabrication along with appropriate surface chemistry, provide a means to fabricate these platforms en masse with flexibility in tailoring the shape, size, reservoir volume, and surface characteristics of microdevices. Moreover, the same technology can be used to include integrated circuit technology and sensors for designing sophisticated autonomous drug delivery devices that promise to significantly improve point of care diagnostic and therapeutic medical applications. This review sheds light on some of the fabrication techniques and addresses a few of the microfabricated devices that can be effectively used for controlled oral drug delivery applications. PMID:22981755

Chirra, Hariharasudhan D.; Desai, Tejal A.

2012-01-01

251

Noninvasive Routes of Proteins and Peptides Drug Delivery  

PubMed Central

Recent advances in the field of pharmaceutical biotechnology have led to the formulation of many protein and peptide-based drugs for therapeutic and clinical application. The route of administration has a significant impact on the therapeutic outcome of a drug. The needle and syringe is a well established choice of protein and peptide delivery which has some drawback related to patient and to formulation such as pain, cost, sterility etc. Thus, the noninvasive routes which were of minor importance as parts of drug delivery in the past have assumed added importance in protein and peptide drug delivery and these include nasal, ophthalmic, buccal, vaginal, transdermal and pulmonary routes. The pharmaceutical scientists have some approaches to develop the formulations for protein and peptide delivery by noninvasive routes. But, due to the physiochemical instability and enzymatic barrier of proteins and peptides there are several hurdle to develop suitable formulation. So there is need of penetration enhancers, enzyme inhibitors and suitable vehicles for noninvasive delivery to increase the bioavailability. In this review, the aim is to focus on the approaches to formulation of protein and peptide based drug administration by noninvasive route. PMID:22707818

Jitendra; Sharma, P. K.; Bansal, Sumedha; Banik, Arunabha

2011-01-01

252

Conundrum and therapeutic potential of curcumin in drug delivery.  

PubMed

Turmeric, the source of the polyphenolic active compound curcumin (diferuloylmethane), has been used extensively in traditional medicine since ancient times as a household remedy against various diseases, including hepatic disorders, cough, sinusitis, rheumatism, and biliary disorders. In the past few decades, a number of studies have been done on curcumin showing its potential role in treating inflammatory disorders, cardiovascular disease, cancer, AIDS, and neurological disorders. However, the main drawback associated with curcumin is its poor aqueous solubility and stability in gastrointestinal fluids, which leads to poor bioavailability. Multifarious novel drug-delivery approaches, including microemulsions, nanoemulsions, liposomes, solid lipid nanoparticles, microspheres, solid dispersion, polymeric nanoparticles, and self-microemulsifying drug-delivery systems have been used to enhance the bioavailability and tissue-targeting ability of curcumin. These attempts have revealed promising results for enhanced bioavailability and targeting to disease such as cancer, but more extensive research on tissue-targeting and stability-related issues is needed. Tissue targeting and enhanced bioavailability of curcumin using novel drug-delivery methods with minimum side effects will in the near future bring this promising natural product to the forefront of therapy for the treatment of human diseases such as cancer and cardiovascular ailments. We provide a detailed analysis of prominent research in the field of curcumin drug delivery with special emphasis on bioavailability-enhancement approaches and novel drug-delivery system approaches. PMID:20932240

Kumar, Anil; Ahuja, Alka; Ali, Javed; Baboota, Sanjula

2010-01-01

253

Novel Strategies for Anterior Segment Ocular Drug Delivery  

PubMed Central

Abstract Research advancements in pharmaceutical sciences have led to the development of new strategies in drug delivery to anterior segment. Designing a new delivery system that can efficiently target the diseased anterior ocular tissue, generate high drug levels, and maintain prolonged and effective concentrations with no or minimal side effects is the major focus of current research. Drug delivery by traditional method of administration via topical dosing is impeded by ocular static and dynamic barriers. Various products have been introduced into the market that prolong drug retention in the precorneal pocket and to improve bioavailability. However, there is a need of a delivery system that can provide controlled release to treat chronic ocular diseases with a reduced dosing frequency without causing any visual disturbances. This review provides an overview of anterior ocular barriers along with strategies to overcome these ocular barriers and deliver therapeutic agents to the affected anterior ocular tissue with a special emphasis on nanotechnology-based drug delivery approaches. PMID:23215539

Cholkar, Kishore; Patel, Sulabh P.; Vadlapudi, Aswani Dutt

2013-01-01

254

Liposomal drug delivery systems: from concept to clinical applications.  

PubMed

The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as drug delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of drugs. These advances have led to numerous clinical trials in such diverse areas as the delivery of anti-cancer, anti-fungal and antibiotic drugs, the delivery of gene medicines, and the delivery of anesthetics and anti-inflammatory drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future. PMID:23036225

Allen, Theresa M; Cullis, Pieter R

2013-01-01

255

Contact lenses as drug reservoirs & delivery systems: the successes & challenges.  

PubMed

Although conventional eye drops comprise over 90% of the marketed ocular dosage forms, they do have limitations, such as poor ocular drug bioavailability and systemic side effects; contact lenses are amongst the new delivery systems and devices that could overcome some of these problems. The most common approach to load drug molecules into contact lenses includes soaking in a drug solution. This approach had some success, but failed to achieve controlled/sustained drug release to the eye. One the other hand, nanoreservoir systems comprising nanoparticles, cyclodextrins, liposomes or surfactant aggregates being incorporated into the contact lenses could offer a plausible solution. This review highlights the status quo with contact lenses as ocular drug-delivery carriers and identifies possible future directions. PMID:25418268

ElShaer, Amr; Ghatora, Baljit; Mustafa, Shelan; Alany, Raid G

2014-10-01

256

P-glycoprotein Inhibition for Optimal Drug Delivery  

PubMed Central

P-glycoprotein (P-gp), an efflux membrane transporter, is widely distributed throughout the body and is responsible for limiting cellular uptake and the distribution of xenobiotics and toxic substances. Hundreds of structurally diverse therapeutic agents are substrates to it and it impedes the absorption, permeability, and retention of the drugs, extruding them out of the cells. It is overexpressed in cancer cells and accountable for obstructing cell internalization of chemotherapeutic agents and for developing transporter mediated resistance by cancer cells during anti-tumor treatments. As it jeopardizes the success of drug delivery and cancer targeting, strategies are being developed to overcome P-gp mediated drug transport. This concise review represents a brief discussion on P-gp mediated drug transport and how it hinders the success of various therapies. Its main focus is on various strategies used to tackle this curb in the field of drug delivery and targeting. PMID:24023511

Amin, Md. Lutful

2013-01-01

257

Nanostructured materials for selective recognition and targeted drug delivery  

NASA Astrophysics Data System (ADS)

Selective recognition requires the introduction of a molecular memory into a polymer matrix in order to make it capable of rebinding an analyte with a very high specificity. In addition, targeted drug delivery requires drug-loaded vesicles which preferentially localize to the sites of injury and avoid uptake into uninvolved tissues. The rapid evolution of nanotechnology is aiming to fulfill the goal of selective recognition and optimal drug delivery through the development of molecularly imprinted polymeric (MIP) nanoparticles, tailor-made for a diverse range of analytes (e.g., pharmaceuticals, pesticides, amino acids, etc.) and of nanostructured targeted drug carriers (e.g., liposomes and micelles) with increased circulation lifetimes. In the present study, PLGA microparticles containing multilamellar vesicles (MLVs), and MIP nanoparticles were synthesized to be employed as drug carriers and synthetic receptors respectively.

Kotrotsiou, O.; Kotti, K.; Dini, E.; Kammona, O.; Kiparissides, C.

2005-01-01

258

Designer lipids for drug delivery: from heads to tails.  

PubMed

For four decades, liposomes composed of both naturally occurring and synthetic lipids have been investigated as delivery vehicles for low molecular weight and macromolecular drugs. These studies paved the way for the clinical and commercial success of a number of liposomal drugs, each of which required a tailored formulation; one liposome size does not fit all drugs! Instead, the physicochemical properties of the liposome must be matched to the pharmacology of the drug. An extensive biophysical literature demonstrates that varying lipid composition can influence the size, membrane stability, in vivo interactions, and drug release properties of a liposome. In this review we focus on recently described synthetic lipid headgroups, linkers and hydrophobic domains that can provide control over the intermolecular forces, phase preference, and macroscopic behavior of liposomes. These synthetic lipids further our understanding of lipid biophysics, promote targeted drug delivery and improve liposome stability. We further highlight the immune reactivity of novel synthetic headgroups as a key design consideration. For instance it was originally thought that synthetic PEGylated lipids were immunologically inert; however, it's been observed that under certain conditions PEGylated lipids induce humoral immunity. Such immune activation may be a limitation to the use of other engineered lipid headgroups for drug delivery. In addition to the potential immunogenicity of engineered lipids, future investigations on liposome drugs in vivo should pay particular attention to the location and dynamics of payload release. PMID:24816069

Kohli, Aditya G; Kierstead, Paul H; Venditto, Vincent J; Walsh, Colin L; Szoka, Francis C

2014-09-28

259

Targeted Nanogels: A Versatile Platform for Drug Delivery to Tumors  

PubMed Central

While nanoparticle-based drug delivery formulations can improve the effectiveness and safety of certain anti-cancer drugs, many drugs, due to their chemical composition, are unsuitable for nanoparticle loading. Here, we describe a targeted nanogel drug delivery platform that can 1) encapsulate a wide range of drug chemotypes including: biological, small molecule, and cytotoxic agents 2) display targeting ligands and polymeric coatings on the surface, 3) enhance drug retention within the nanogel core after photo-crosslinking, and 4) retain therapeutic activity after lyophilization allowing for long term storage. For therapeutic studies, we utilized integrin ?v?3-targeted lipid-coated nanogels with crosslinked human serum albumin in the core for carrying therapeutic cargoes. These particles exhibited potent activity in tumor cell viability assays with drugs of distinct chemotype including: paclitaxel, docetaxel, bortezomib, 17-AAG, sorafenib, sunitinib, bosutinib, and dasatinib. Treatment of orthotopic breast and pancreas tumors in mice with taxane-loaded nanogels produced a 15-fold improvement in anti-tumor activity relative to Abraxane by blocking both primary tumor growth and spontaneous metastasis. With a modifiable surface and core, the lipid-coated nanogel represents a platform technology that can be easily adapted for specific drug delivery applications to treat a wide range of malignant diseases. PMID:21518727

Murphy, Eric A.; Majeti, Bharat K.; Mukthavaram, Rajesh; Acevedo, Lisette M.; Barnes, Leo A.; Cheresh, David A.

2011-01-01

260

Nanocrystal technology, drug delivery and clinical applications  

PubMed Central

Nanotechnology will affect our lives tremendously over the next decade in very different fields, including medicine and pharmacy. Transfer of materials into the nanodimension changes their physical properties which were used in pharmaceutics to develop a new innovative formulation principle for poorly soluble drugs: the drug nanocrystals. The drug nanocrystals do not belong to the future; the first products are already on the market. The industrially relevant production technologies, pearl milling and high pressure homogenization, are reviewed. The physics behind the drug nanocrystals and changes of their physical properties are discussed. The marketed products are presented and the special physical effects of nanocrystals explained which are utilized in each market product. Examples of products in the development pipelines (clinical phases) are presented and the benefits for in vivo administration of drug nanocrystals are summarized in an overview. PMID:18990939

Junghanns, Jens-Uwe A H; Müller, Rainer H

2008-01-01

261

IMPLANTABLE MEMS DRUG DELIVERY SYSTEMS FOR ADMINISTRATION OF UNALTERED THERAPEUTIC AGENTS  

E-print Network

IMPLANTABLE MEMS DRUG DELIVERY SYSTEMS FOR ADMINISTRATION OF UNALTERED THERAPEUTIC AGENTS Ellis microelectromechanical systems (MEMS) drug delivery device capable of being refilled for targeted intraocular delivery delivery vehicle for treating difficult-to-reach diseases affecting the posterior segment of the eye. Drug

Meng, Ellis

262

NanoClusters Enhance Drug Delivery in Mechanical Ventilation  

NASA Astrophysics Data System (ADS)

The overall goal of this thesis was to develop a dry powder delivery system for patients on mechanical ventilation. The studies were divided into two parts: the formulation development and the device design. The pulmonary system is an attractive route for drug delivery since the lungs have a large accessible surface area for treatment or drug absorption. For ventilated patients, inhaled drugs have to successfully navigate ventilator tubing and an endotracheal tube. Agglomerates of drug nanoparticles (also known as 'NanoClusters') are fine dry powder aerosols that were hypothesized to enable drug delivery through ventilator circuits. This Thesis systematically investigated formulations of NanoClusters and their aerosol performance in a conventional inhaler and a device designed for use during mechanical ventilation. These engineered powders of budesonide (NC-Bud) were delivered via a MonodoseRTM inhaler or a novel device through commercial endotracheal tubes, and analyzed by cascade impaction. NC-Bud had a higher efficiency of aerosol delivery compared to micronized stock budesonide. The delivery efficiency was independent of ventilator parameters such as inspiration patterns, inspiration volumes, and inspiration flow rates. A novel device designed to fit directly to the ventilator and endotracheal tubing connections and the MonodoseRTM inhaler showed the same efficiency of drug delivery. The new device combined with NanoCluster formulation technology, therefore, allowed convenient and efficient drug delivery through endotracheal tubes. Furthermore, itraconazole (ITZ), a triazole antifungal agent, was formulated as a NanoCluster powder via milling (top-down process) or precipitation (bottom-up process) without using any excipients. ITZ NanoClusters prepared by wet milling showed better aerosol performance compared to micronized stock ITZ and ITZ NanoClusters prepared by precipitation. ITZ NanoClusters prepared by precipitation methods also showed an amorphous state while milled ITZ NanoClusters maintained the crystalline character. Overall, NanoClusters prepared by various processes represent a potential engineered drug particle approach for inhalation therapy since they provide effective aerosol properties and stability due to the crystalline state of the drug powders. Future work will continue to explore formulation and delivery performance in vitro and in vivo..

Pornputtapitak, Warangkana

263

Nanoscale drug delivery systems and the blood–brain barrier  

PubMed Central

The protective properties of the blood–brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain’s vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual’s age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS. PMID:24550672

Alyautdin, Renad; Khalin, Igor; Nafeeza, Mohd Ismail; Haron, Muhammad Huzaimi; Kuznetsov, Dmitry

2014-01-01

264

Biologically erodable microspheres as potential oral drug delivery systems  

Microsoft Academic Search

Biologically adhesive delivery systems offer important advantages1-5 over conventional drug delivery systems6. Here we show that engineered polymer microspheres made of biologically erodable polymers, which display strong adhesive interactions with gastrointestinal mucus and cellular linings, can traverse both the mucosal absorptive epithelium and the follicle-associated epithelium covering the lymphoid tissue of Peyer's patches. The polymers maintain contact with intestinal epithelium

Edith Mathiowitz; Jules S. Jacob; Yong S. Jong; Gerardo P. Carino; Donald E. Chickering; Pravin Chaturvedi; Camilla A. Santos; Kavita Vijayaraghavan; Sean Montgomery; Michael Bassett; Craig Morrell

1997-01-01

265

The PulmoSphere™ platform for pulmonary drug delivery.  

PubMed

Spray-dried PulmoSphere™ formulations comprise phospholipid-based small, porous particles. Drug(s) may be incorporated in or with PulmoSphere formulations in three formats: solution-, suspension-, and carrier-based systems. The multiple formats may be administered to the respiratory tract with multiple delivery systems, including portable inhalers (pressurized, metered-dose inhaler and dry-powder inhaler), nebulizers, and via liquid dose instillation in conjunction with partial liquid ventilation. The PulmoSphere platform (particles, formats, delivery systems) enables pulmonary delivery of a broad range of drugs independent of their physicochemical properties and lung dose. The engineered particles provide significant improvements in lung targeting and dose consistency, relative to current marketed inhalers. PMID:24592954

Weers, Jeffry; Tarara, Thomas

2014-03-01

266

Controlled Release of Simvastatin from Biomimetic ?-TCP Drug Delivery System  

PubMed Central

Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate delivery system to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drug delivery system for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drug delivery system for simvastatin. PMID:23349949

Chou, Joshua; Ito, Tomoko; Bishop, David; Otsuka, Makoto; Ben-Nissan, Besim; Milthorpe, Bruce

2013-01-01

267

Controlled release of simvastatin from biomimetic ?-TCP drug delivery system.  

PubMed

Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate delivery system to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drug delivery system for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drug delivery system for simvastatin. PMID:23349949

Chou, Joshua; Ito, Tomoko; Bishop, David; Otsuka, Makoto; Ben-Nissan, Besim; Milthorpe, Bruce

2013-01-01

268

Connecting drug delivery reality to smart materials design.  

PubMed

Inflated claims to both design and mechanistic novelty in drug delivery and imaging systems, including most nanotechnologies, are not supported by the generally poor translation of these systems to clinical efficacy. The "form begets function" design paradigm is seductive but perhaps over-simplistic in translation to pharmaceutical efficacy. Most innovations show few clinically important distinctions in their therapeutic benefits in relevant preclinical disease and delivery models, despite frequent claims to the contrary. Long-standing challenges in drug delivery issues must enlist more realistic, back-to-basics approaches to address fundamental materials properties in complex biological systems, preclinical test beds, and analytical methods to more reliably determine fundamental pharmaceutical figures of merit, including drug carrier purity and batch-batch variability, agent biodistribution, therapeutic index (safety), and efficacy. PMID:23624177

Grainger, David W

2013-09-15

269

Microbubbles in Ultrasound-Triggered Drug and Gene Delivery  

PubMed Central

Ultrasound contrast agents, in the form of gas-filled microbubbles, are becoming popular in perfusion monitoring; they are employed as molecular imaging agents. Microbubbles are manufactured from biocompatible materials, they can be injected intravenously, and some are approved for clinical use. Microbubbles can be destroyed by ultrasound irradiation. This destruction phenomenon can be applied to targeted drug delivery and enhancement of drug action. The ultrasonic field can be focused at the target tissues and organs; thus, selectivity of the treatment can be improved, reducing undesirable side effects. Microbubbles enhance ultrasound energy deposition in the tissues and serve as cavitation nuclei, increasing intracellular drug delivery. DNA delivery and successful tissue transfection is observed in the areas of the body where ultrasound is applied after intravascular administration of microbubbles and plasmid DNA. Accelerated blood clot dissolution in the areas of insonation by cooperative action of thrombolytic agents and microbubbles is demonstrated in several clinical trials. PMID:18486268

Hernot, Sophie; Klibanov, Alexander L.

2008-01-01

270

PEGylated rosin derivatives: novel microencapsulating materials for sustained drug delivery.  

PubMed

The aim of this study was to investigate PEGylated rosin derivatives (PRDs) as microencapsulating materials for sustained drug delivery. PRDs (D1, D2, and D3) composed of a constant weight of rosin and varied amounts of polyethylene glycol (PEG) 400 and maleic anhydride were synthesized in the laboratory. Microparticles were prepared by the O/O solvent evaporation technique using the acetone/paraffin system. Diclofenac sodium (DFS) and diltiazem hydrochloride (DLTZ) were used as model drugs. The effect of the type of PRD, drug, PRD:drug ratio, viscosity of external phase, stirring speed, concentration of magnesium stearate (droplet stabilizer), and method of preparation on particle size, drug loading, and drug release profiles of microparticles was investigated. PRDs could produce discrete and spherical microspheres (with DFS) and microcapsules (with DLTZ). The drug loading value for microparticles was found to be in the range of 37.21% to 87.90%. The microparticle size range was 14 to 36 microm. The particle size and drug loadings of microparticles were substantially affected by the concentration of magnesium stearate and the type of drug, respectively. Most of the formulations could sustain the DFS and DLTZ release for 20 hours. DFS and DLTZ release from PRD microparticles followed Hixson-Crowell and first-order kinetics, respectively. The results suggest that PRDs can be used successfully to prepare discrete and spherical microparticles with DFS and DLTZ for sustained drug delivery. PMID:17622122

Morkhade, Dinesh M; Nande, Vishwanath S; Barabde, Umesh V; Patil, Arun T; Joshi, Siddheshwar B

2007-01-01

271

Localized Cell and Drug Delivery for Auditory Prostheses  

PubMed Central

Localized cell and drug delivery to the cochlea and central auditory pathway can improve the safety and performance of implanted auditory prostheses (APs). While generally successful, these devices have a number of limitations and adverse effects including limited tonal and dynamic ranges, channel interactions, unwanted stimulation of non-auditory nerves, immune rejection, and infections including meningitis. Many of these limitations are associated with the tissue reactions to implanted auditory prosthetic devices and the gradual degeneration of the auditory system following deafness. Strategies to reduce the insertion trauma, degeneration of target neurons, fibrous and bony tissue encapsulation, and immune activation can improve the viability of tissue required for AP function as well as improve the resolution of stimulation for reduced channel interaction and improved place-pitch and level discrimination. Many pharmaceutical compounds have been identified that promote the viability of auditory tissue and prevent inflammation and infection. Cell delivery and gene therapy have provided promising results for treating hearing loss and reversing degeneration. Currently, many clinical and experimental methods can produce extremely localized and sustained drug delivery to address AP limitations. These methods provide better control over drug concentrations while eliminating the adverse effects of systemic delivery. Many of these drug delivery techniques can be integrated into modern auditory prosthetic devices to optimize the tissue response to the implanted device and reduce the risk of infection or rejection. Together, these methods and pharmaceutical agents can be used to optimize the tissue-device interface for improved AP safety and effectiveness. PMID:18573323

Hendricks, Jeffrey L.; Chikar, Jennifer A.; Crumling, Mark A.; Raphael, Yehoash; Martin, David C.

2011-01-01

272

Novel drug-delivery systems for patients with chronic rhinosinusitis  

PubMed Central

Chronic rhinosinusitis, one of the most common chronic medical complaints in the United States, seems to be increasing in incidence and prevalence, and has a significant impact on quality of life. Topical forms of medical therapy represent an attractive alternative for drug delivery to the nasal cavity and paranasal sinuses. Topical drug delivery has the advantage of directly acting on the site of inflammation, producing a higher concentration at the target site while avoiding systemic side effects. Although considerable research has been undertaken into improving nasal formulations in order to enhance absorption, little attention has so far been directed to upgrading the delivery devices. The aim of this review is to present current knowledge on the novel drug-delivery devices in use in the management of chronic rhinosinusitis patients, and to present the current available knowledge on topical drug penetration into the sinuses using various delivery devices. Additionally, methods used to enhance fluid sinus deposition are presented and the published clinical studies on the results of nebulized antibiotics in the treatment of chronic rhinosinusitis patients are discussed. PMID:22745531

Albu, Silviu

2012-01-01

273

Oral colon-specific drug delivery of protein and peptide drugs.  

PubMed

With the advent of new technologies and radical growth in the field of biotechnology, dozens of protein and peptide drugs have been marketed. However, there are several challenges for successful delivery of such molecules. A number of routes have been used for the delivery of these fragile molecules by exploring various novel delivery technologies, including microspheres, liposomes, gel spheres, nano-spheres, niosomes, microemulsions, use of permeation enhancers, use of protease inhibitors, etc. But the route that has attracted the attention of worldwide drug delivery scientists is the oral route due to its various advantages. Even though the proteolytic activity is higher in a few segments of the gastrointestinal tract (GIT), this route has certain segments that have lower proteolytic activity, for example, the colon. The colon has captured attention as a site for the delivery of these molecules because of its greater responsiveness to absorption enhancers, protease inhibitors, and novel bioadhesive and biodegradable polymers. Although the success rate of these approaches, when used alone is pretty low, when used in combinations, these agents have demonstrated wonders in increasing the drug bioavailability. This review focuses on the challenges, pharmaceutical concepts, and approaches involved in the delivery of these fragile molecules, specifically to the colon. This review also includes studies conducted on colonic targeting of such drugs. Further studies may lead to improvements in therapy using protein/peptide drugs and refinements in the technology of colon-specific drug delivery. PMID:17430100

Sinha, V; Singh, Asmita; Kumar, Ruchita V; Singh, Sanjay; Kumria, Rachana; Bhinge, J

2007-01-01

274

Intravesical drug delivery: Challenges, current status, opportunities and novel strategies.  

PubMed

The urinary bladder has certain unique anatomical features which enable it to form an effective barrier to toxic substances diffusing from the urine into the blood. The barrier function is due to the epithelial surface of the urinary bladder, the urothelium, which has characteristic umbrella cells, joined by tight junctions and covered by impenetrable plaques, as well as an anti-adherent mucin layer. Diseases of the urinary bladder, such as bladder carcinomas and interstitial cystitis, cause acute damage to the bladder wall and cannot be effectively treated by systemic administration of drugs. Such conditions may benefit from intravesical drug delivery (IDD), which involves direct instillation of drug into the bladder via a catheter, to attain high local concentrations of the drug with minimal systemic effects. IDD however has its limitations, since the permeability of the urothelial layer is very low and instilled drug solutions become diluted with urine and get washed out of the bladder during voiding, necessitating repeated infusions of the drug. Permeation enhancers serve to overcome these problems to some extent by using electromotive force to enhance diffusion of the drug into the bladder wall or chemical molecules, such as chitosan, dimethylsulphoxide, to temporarily disrupt the tight packing of the urothelium. Nanotechnology can be integrated with IDD to devise drug-encapsulated nanoparticles that can greatly improve chemical interactions with the urothelium and enhance penetration of drugs into the bladder wall. Nanocarriers such as liposomes, gelatin nanoparticles, polymeric nanoparticles and magnetic particles, have been found to enhance local drug concentrations in the bladder as well as target diseased cells. Intravesical drug carriers can be further improved by using mucoadhesive biomaterials which are strongly adhered to the urothelial cell lining, thus preventing the carrier from being washed away during urine voiding. This increases the residence time of the drug at the target site and enables sustained delivery of the drug over a prolonged time span. Polymeric hydrogels, such as the temperature sensitive PEG-PLGA-PEG polymer, have been used to develop in situ gelling systems to deliver drugs into the bladder cavity. Recent advances and future prospects of biodegradable nanocarriers and in situ gels as drug delivery agents for intravesical drug delivery are reviewed in this paper. PMID:20831887

GuhaSarkar, Shruti; Banerjee, R

2010-12-01

275

Transdermal drug delivery by localized intervention  

E-print Network

Both field-confined skin electroporation and microscissioning offer minimally invasive methods for delivering drugs across skin and nail with minimal sensation. Both methods create high permeability pathways in a pain-free ...

Weaver, James C.

276

Biophysical interactions with model lipid membranes: applications in drug discovery and drug delivery  

PubMed Central

The transport of drugs or drug delivery systems across the cell membrane is a complex biological process, often difficult to understand because of its dynamic nature. In this regard, model lipid membranes, which mimic many aspects of cell-membrane lipids, have been very useful in helping investigators to discern the roles of lipids in cellular interactions. One can use drug-lipid interactions to predict pharmacokinetic properties of drugs, such as their transport, biodistribution, accumulation, and hence efficacy. These interactions can also be used to study the mechanisms of transport, based on the structure and hydrophilicity/hydrophobicity of drug molecules. In recent years, model lipid membranes have also been explored to understand their mechanisms of interactions with peptides, polymers, and nanocarriers. These interaction studies can be used to design and develop efficient drug delivery systems. Changes in the lipid composition of cells and tissue in certain disease conditions may alter biophysical interactions, which could be explored to develop target-specific drugs and drug delivery systems. In this review, we discuss different model membranes, drug-lipid interactions and their significance, studies of model membrane interactions with nanocarriers, and how biophysical interaction studies with lipid model membranes could play an important role in drug discovery and drug delivery. PMID:19432455

Peetla, Chiranjeevi; Stine, Andrew; Labhasetwar, Vinod

2009-01-01

277

Intelligent drug delivery systems obtained by radiation  

NASA Astrophysics Data System (ADS)

Radiation-induced polymerization of acryloyl-L-proline methyl ester, an ?-aminoacid-containing monomer, in the presence of a crosslinking agent and a hydrophilic monomer gave rise to polymer hydrogels whose water content at equilibrium was found to decrease as the swelling temperature increased. Some hydrogel samples were obtained with entrapped acetaminophen, an analgesic and antipyretic drug. It was ascertained that the release of the drug was controlled by both the hydrophilicity of the polymer matrices and the environmental temperature.

Martellini, Flavia; Higa, Olga Z.; Takacs, Erzsebet; Safranj, Agneza; Yoshida, Masaru; Katakai, Ryoichi; Carenza, Mario

1998-06-01

278

Pulmonary drug delivery. Part II: The role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications  

PubMed Central

Research in the area of pulmonary drug delivery has gathered momentum in the last several years, with increased interest in using the lung as a means of delivering drugs systemically. Advances in device technology have led to the development of more efficient delivery systems capable of delivering larger doses and finer particles into the lung. As more efficient pulmonary delivery devices and sophisticated formulations become available, physicians and health professionals will have a choice of a wide variety of device and formulation combinations that will target specific cells or regions of the lung, avoid the lung's clearance mechanisms and be retained within the lung for longer periods. It is now recognized that it is not enough just to have inhalation therapy available for prescribing; physicians and other healthcare providers need a basic understanding of aerosol science, inhaled formulations, delivery devices, and bioequivalence of products to prescribe these therapies optimally. PMID:14616419

Labiris, N R; Dolovich, M B

2003-01-01

279

Microneedles for intradermal and transdermal drug delivery.  

PubMed

The formidable barrier properties of the uppermost layer of the skin, the stratum corneum, impose significant limitations for successful systemic delivery of broad range of therapeutic molecules particularly macromolecules and genetic material. Microneedle (MN) has been proposed as a strategy to breach the stratum corneum barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves use of micron sized needles fabricated of different materials and geometries to create transient aqueous conduits across the skin. MN, alone or with other enhancing strategies, has been demonstrated to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo experiments. This suggested the promising use of MN technology for various possible clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. MN has been proved as minimally invasive and painless in human subjects. This review article focuses on recent and future developments for MN technology including the latest type of MN design, challenges and strategies in MNs development as well as potential safety aspects based on comprehensive literature review pertaining to MN studies to date. PMID:23680534

Tuan-Mahmood, Tuan-Mazlelaa; McCrudden, Maelíosa T C; Torrisi, Barbara M; McAlister, Emma; Garland, Martin J; Singh, Thakur Raghu Raj; Donnelly, Ryan F

2013-12-18

280

Drug delivery strategies for therapeutic angiogenesis and antiangiogenesis  

PubMed Central

Introduction Angiogenesis is essential to human biology and of great clinical significance. Excessive or reduced angiogenesis can result in, or exacerbate, several disease states, including tumor formation, exudative age-related macular degeneration (AMD) and ischemia. Innovative drug delivery systems can increase the effectiveness of therapies used to treat angiogenesis-related diseases. Areas covered This paper reviews the basic biology of angiogenesis, including current knowledge about its disruption in diseases, with the focus on cancer and AMD. Anti- and proangiogenic drugs available for clinical use or in development are also discussed, as well as experimental drug delivery systems that can potentially improve these therapies to enhance or reduce angiogenesis in a more controlled manner. Expert opinion Laboratory and clinical results have shown pro- or antiangiogenic drug delivery strategies to be effective in drastically slowing disease progression. Further research in this area will increase the efficacy, specificity and duration of these therapies. Future directions with composite drug delivery systems may make possible targeting of multiple factors for synergistic effects. PMID:21338327

Bhise, Nupura S; Shmueli, Ron B; Sunshine, Joel C; Tzeng, Stephany Y; Green, Jordan J

2014-01-01

281

Biocompatibility of Chitosan Carriers with Application in Drug Delivery  

PubMed Central

Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures. PMID:24955636

Rodrigues, Susana; Dionísio, Marita; Remuñán López, Carmen; Grenha, Ana

2012-01-01

282

Controlling the morphology of electrospray-generated PLGA microparticles for drug delivery  

E-print Network

Controlling the morphology of electrospray-generated PLGA microparticles for drug delivery Begoña drug delivery Morphology Entanglements Coulomb fission Multiplexing a b s t r a c t We developed a well, improve drug stability and bioavailability, and ex- tend drug or gene effect through sustained delivery

Gomez, Alessandro

283

DRUG DELIVERY IN BIOLOGICAL TISSUES: AN APPLICATION TO THE ELUTING STENT  

E-print Network

DRUG DELIVERY IN BIOLOGICAL TISSUES: AN APPLICATION TO THE ELUTING STENT G. Pontrelli1 , F. de and a quantitative description for drug transport to evaluate feasibility of new drug delivery strategies purposes is becoming quite common in medicine nowadays, through drug delivery devices [1]. The mechanism

Pontrelli, Giuseppe

284

Modeling doxorubicin transport to improve intratumoral drug delivery to RF ablated tumors  

E-print Network

Modeling doxorubicin transport to improve intratumoral drug delivery to RF ablated tumors Brent D of drug transport provides an ideal strategy to optimize intratumoral drug delivery implants to supplement) simulations of drug delivery from implants with and without RF thermal ablation underscore the benefit

Gao, Jinming

285

PLGAlecithinPEG coreshell nanoparticles for controlled drug delivery Juliana M. Chan a  

E-print Network

PLGA­lecithin­PEG core­shell nanoparticles for controlled drug delivery Juliana M. Chan drug release Drug delivery Liposome Nanoparticle Polyethylene oxide Self-assembly a b s t r a c that the PLGA­lecithin­PEG core­shell NPs may be a useful new controlled release drug delivery system. Published

Zhang, Liangfang

286

Advanced Drug Delivery Reviews 48 (2001) 137138 www.elsevier.com/locate/drugdeliv  

E-print Network

Advanced Drug Delivery Reviews 48 (2001) 137­138 www.elsevier.com/locate/drugdeliv Preface Mathematical modeling of controlled drug delivery Mathematical modeling of controlled drug deliv- This special of mathematical theories de- involved. scribing drug release from controlled delivery sys- Very often, polymers

Peppas, Nicholas A.

287

Design and Testing of an Impedance-Based Sensor for Monitoring Drug Delivery  

E-print Network

Design and Testing of an Impedance-Based Sensor for Monitoring Drug Delivery Audrey M. Johnson, Massachusetts 02139, USA A new impedance-based sensor to monitor drug delivery from an implantable of the model drug mannitol from the drug delivery MEMS device. The measured solution resistance and double

Sadoway, Donald Robert

288

Dendritic polymer-based nanodevices for targeted drug delivery applications  

NASA Astrophysics Data System (ADS)

Dendrimers and hyperbranched polymers are unimolecular micellar nanostructures, characterized by globular shape ( ˜ 20 nm) and large density of functional groups at periphery. The tailorable end groups make them ideal for conjugation with drugs, ligands, and imagining agents, making them an attractive molecular nanodevices for drug delivery. Compared to linear polymers and nanoparticles, these nanodevices enter cells rapidly, carrying drugs and delivering them inside cells. Performance of nanodevices prepared for asthma and cancer drug delivery will be discussed. Our conjugation procedure produced very high drug payloads. Dendritic polymer-drug conjugates were very effective in transporting methotrexate (a chemotherapy drug) into both sensitive (CCRF-CEM cell line) and resistant cell line (CEM-MTX). The conjugate nanodevice was 3 times more effective than free drug in the sensitive line, and 9 times more effective in the resistant cell line (based on IC50). The physics of cell entry and drug release from these nanodevices are being investigated. The conjugates appear to enter cells through endocytosis, with the rate of entry dependent on end-group, molecular weight, the pH of the medium, and the cancerous nature of the cells.

Kannan, R. M.; Kolhe, Parag; Gurdag, Sezen; Khandare, Jayant; Lieh-Lai, Mary

2004-03-01

289

Development and characterization of stable nanovesicular carrier for drug delivery.  

PubMed

Lipid vesicles are an important drug carrier which can serve for controlled delivery of drugs; however, these vesicles are quite unstable at ambient temperature and require stringent storage condition. Present work was done to develop a stable vesicular system for drug delivery. Vesicles of ceramide-2, cholesterol, cholesterol sulfate, and palmitic acid were prepared and compared with phosphatidylcholine vesicles for physicochemical parameters and accelerated stability. Diclofenac sodium was used as a model drug. Based on physicochemical parameter and in vitro release PCV-3 and CV-3 were selected for further studies in three different accelerated stability conditions. PCV-3 showed moderate changes at 4°C but was severely affected at 25°C and 40°C. CV-3 showed stable characteristics at 4°C and 25°C whereas at 40°C, CV-3 showed signs of slight modification owing to moisture absorption. Based on the study, CV-3 containing highest content of palmitic acid was found to be most stable. PMID:23865793

Gaur, Praveen Kumar; Purohit, Suresh; Kumar, Yatendra; Mishra, Shikha; Bhandari, Anil

2014-10-01

290

[Intravitreal drug delivery by microspheres of biodegradable polymers].  

PubMed

We evaluated the efficacy of microspheres of biodegradable polymers as a slow releasing drug delivery system in the vitreous body. Microspheres containing 5-FU were prepared with polymers of poly-(lactic acid) or copolymers of glycolic acid and lactic acid. The release of the drug was studied in vitro. Poly-(lactic acid) microspheres released 5-FU for 7 days. The intravitreal kinetics of the microspheres was studied in rabbits in vivo. The microspheres disappeared from the vitreous cavity of normal eyes by 48 +/- 5 days after injection. Disappearance was accelerated from the vitreous cavity of vitrectomized rabbits (14 +/- 2 days, p less than 10(-6)). No abnormality was found on electroretinographic or histological examinations after microspheres injection. These results suggested that microspheres of biodegradable polymers could be useful as a potential drug delivery system for sustained drug release in the vitreous body. PMID:2220493

Moritera, T; Ogura, Y; Honda, Y; Wada, R; Hyon, S H; Ikada, Y

1990-05-01

291

Inhaled formulations and pulmonary drug delivery systems for respiratory infections.  

PubMed

Respiratory infections represent a major global health problem. They are often treated by parenteral administrations of antimicrobials. Unfortunately, systemic therapies of high-dose antimicrobials can lead to severe adverse effects and this calls for a need to develop inhaled formulations that enable targeted drug delivery to the airways with minimal systemic drug exposure. Recent technological advances facilitate the development of inhaled anti-microbial therapies. The newer mesh nebulisers have achieved minimal drug residue, higher aerosolisation efficiencies and rapid administration compared to traditional jet nebulisers. Novel particle engineering and intelligent device design also make dry powder inhalers appealing for the delivery of high-dose antibiotics. In view of the fact that no new antibiotic entities against multi-drug resistant bacteria have come close to commercialisation, advanced formulation strategies are in high demand for combating respiratory 'super bugs'. PMID:25451137

Zhou, Qi Tony; Leung, Sharon Shui Yee; Tang, Patricia; Parumasivam, Thaigarajan; Loh, Zhi Hui; Chan, Hak-Kim

2014-10-24

292

Hybrid microparticles for drug delivery and magnetic resonance imaging.  

PubMed

In this work, we report the synthesis, characterization, and possible application as drug-delivery system magnetically triggered, of hybrid microparticles formed by magnetic nanoparticles embedded within poly(?-caprolactone). The magnetism of the microparticles permits their localization within the body using magnetic resonance imaging, and the biodegradable polymer layer allows entrapping drugs that can be released when temperature increases. The synthesis of the hybrid material was performed using "grafting from" technique of conveniently modified magnetic nanoparticles. Subsequently, the resulting hybrid nanoparticles were assembled into spherical particles of 138 ± 49 nm via precipitation technique. The produced hybrid material was evaluated as stimuli-responsive drug delivery system in which the release of the drug was triggered by magnetic induction. Furthermore, the microparticles were injected in rats and their localization within the animal was monitored using the local field inhomogeneities generated by the particles. PMID:22915497

Serrano-Ruiz, David; Laurenti, Marco; Ruiz-Cabello, Jesús; López-Cabarcos, Enrique; Rubio-Retama, Jorge

2013-05-01

293

Potential and problems in ultrasound-responsive drug delivery systems  

PubMed Central

Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. PMID:23637531

Zhao, Ying-Zheng; Du, Li-Na; Lu, Cui-Tao; Jin, Yi-Guang; Ge, Shu-Ping

2013-01-01

294

Combination Drug Delivery Approaches in Metastatic Breast Cancer  

PubMed Central

Disseminated metastatic breast cancer needs aggressive treatment due to its reduced response to anticancer treatment and hence low survival and quality of life. Although in theory a combination drug therapy has advantages over single-agent therapy, no appreciable survival enhancement is generally reported whereas increased toxicity is frequently seen in combination treatment especially in chemotherapy. Currently used combination treatments in metastatic breast cancer will be discussed with their challenges leading to the introduction of novel combination anticancer drug delivery systems that aim to overcome these challenges. Widely studied drug delivery systems such as liposomes, dendrimers, polymeric nanoparticles, and water-soluble polymers can concurrently carry multiple anticancer drugs in one platform. These carriers can provide improved target specificity achieved by passive and/or active targeting mechanisms. PMID:22619725

Lee, Jun H.; Nan, Anjan

2012-01-01

295

In vivo Evaluation of Self Emulsifying Drug Delivery System for Oral Delivery of Nevirapine  

PubMed Central

Nevirapine is a highly lipophilic and water insoluble non-nucleoside reverse transcriptase inhibitor used for the treatment of HIV-1 infection. Lymphoid tissue constitutes the major reservoir of HIV virus and infected cells in HIV-infected patients. Self-emulsifying drug delivery system, using long chain triglycerides, is a popular carrier of drugs due to their ability to transport lipophilic drugs into the lymphatic circulation. However, HIV/AIDS patients experience a variety of functional and anatomical abnormalities in gastrointestinal tract that result in diarrhoea and nutrient malabsorption. Medium chain triglycerides are readily absorbed from the small bowel under conditions in which the absorption of long chain triglycerides is impaired. Therefore, nevirapine self-emulsifying drug delivery system containing medium chain fatty acid, caprylic acid and a solubilizer, Soluphor® P (2-pyrrolidone) was developed and found to be superior to the marketed conventional suspension with respect to in vitro diffusion and ex vivo intestinal permeability. This self-emulsifying drug delivery system has now been further investigated for in vivo absorption in an animal model. The contribution of caprylic acid and Soluphor® P on in vivo absorption of nevirapine was also studied in the present study. The bioavailability of nevirapine from self-emulsifying drug delivery system, after oral administration, was 2.69 times higher than that of the marketed suspension. The improved bioavailability could be due to absorption of nevirapine via both portal and intestinal lymphatic routes. The study indicates that medium chain or structured triglycerides can be a better option to develop self-emulsifying drug delivery system for lipophilic and extensively metabolised drugs like nevirapine for patients with AIDS-associated malabsorption. PMID:25035533

Chudasama, A. S.; Patel, V. V.; Nivsarkar, M.; Vasu, Kamala K.; Shishoo, C. J.

2014-01-01

296

Packaged Au-PPy valves for drug delivery systems  

NASA Astrophysics Data System (ADS)

The most common methods for the drug delivery are swallowing pills or receiving injections. However, formulations that control the rate and period of medicine (i.e., time-release medications) are still problematic. The proposed implantable devices which include batteries, sensors, telemetry, valves, and drug storage reservoirs provide an alternative method for the responsive drug delivery system [1]. Using this device, drug concentration can be precisely controlled which enhances drug efficiency and decreases the side effects. In order to achieve responsive drug delivery, a reliable release valve has to be developed. Biocompatibility, low energy consumption, and minimized leakage are the main requirements for such release method. A bilayer structure composed of Au/PPy film is fabricated as a flap to control the release valve. Optimized potentiostatic control to synthesize polypyrrole (PPy) is presented. The release of miniaturize valve is tested and showed in this paper. A novel idea to simultaneously fabricate the device reservoirs as well as protective packaging is proposed in this paper. The solution of PDMS permeability problem is also mentioned in this article.

Tsai, Han-Kuan A.; Ma, Kuo-Sheng; Zoval, Jim; Kulinsky, Lawrence; Madou, Marc

2006-03-01

297

Nanoengineered drug delivery systems for enhancing antibiotic therapy.  

PubMed

Formulation scientists are recognizing nanoengineered drug delivery systems as an effective strategy to overcome limitations associated with antibiotic drug therapy. Antibiotics encapsulated into nanodelivery systems will contribute to improved management of patients with various infectious diseases and to overcoming the serious global burden of antibiotic resistance. An extensive review of several antibiotic-loaded nanocarriers that have been formulated to target drugs to infectious sites, achieve controlled drug release profiles, and address formulation challenges, such as low-drug entrapment efficiencies, poor solubility and stability is presented in this paper. The physicochemical properties and the in vitro/in vivo performances of various antibiotic-loaded delivery systems, such as polymeric nanoparticles, micelles, dendrimers, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanohybirds, nanofibers/scaffolds, nanosheets, nanoplexes, and nanotubes/horn/rods and nanoemulsions, are highlighted and evaluated. Future studies that will be essential to optimize formulation and commercialization of these antibiotic-loaded nanosystems are also identified. The review presented emphasizes the significant formulation progress achieved and potential that novel nanoengineered antibiotic drug delivery systems have for enhancing the treatment of patients with a range of infections. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:872-905, 2015. PMID:25546108

Kalhapure, Rahul S; Suleman, Nadia; Mocktar, Chunderika; Seedat, Nasreen; Govender, Thirumala

2015-03-01

298

Novel polyoxazolines polymer drug delivery platform  

E-print Network

/w and a high loading efficiency of more than 80%. Figure 1: Tumor inhibition of polyoxazoline micelles loaded drugs showed at least similar effect with regard to tumor inhibition compared to commercial available-resistant (MCF7) human adenocarcinoma cells and Madin-Darby canine kidney (MDCK) cells. All polymers were found

299

Pharmaceutics and drug delivery aspects of heme and porphyrin therapy.  

PubMed

The importance of porphyrins and metalloporphyrins as therapeutic drugs has increased significantly over the last decade. This review highlights some of the challenges faced by pharmaceutical scientists in formulating these drugs into stable, effective, and safe dosage forms. Most activity in the clinic has focused on three areas: photodynamic therapy of cancer (e.g., hematoporphyrin derivatives), porphyrias and hematological diseases (e.g., heme), and various forms of jaundice (e.g., tin porphyrins). The biodistribution, stability, aggregation, toxicology, and analytical methodology of porphyrin drugs are all important considerations in the pharmaceutical development of porphyrin drugs. The utility of delivery systems such as liposomes hold promise of increasing the therapeutic potential of these drugs. Future prospects for therapeutic applications of porphyrin drugs are also discussed. PMID:8360819

Cannon, J B

1993-05-01

300

Fluocinolone acetonide sustained drug delivery device to treat severe uveitis  

Microsoft Academic Search

PurposeUveitis is often a chronic disease requiring long-term medical therapy. In this report, we describe a pilot safety and efficacy trial of a novel sustained drug delivery system containing fluocinolone acetonide to treat patients with severe uveitis.

Glenn J Jaffe; Joshua Ben-nun; Hong Guo; James P Dunn; Paul Ashton

2000-01-01

301

Self Emulsifying Drug Delivery System (SEDDS) for Phytoconstituents: a Review.  

PubMed

The self emulsifying drug delivery system (SEDDS) is considered to be the novel technique for the delivery of lipophillic plant actives. The herbals as self emulsifying (SE) formulation significantly enhance the solubility and bioavailability of poorly aqueous soluble phytoconstituents. The self emulsifying drug delivery system (SEDDS) can be developed for such plant actives to enhance the oral bioavailability using different excipients (lipid, surfactant, co solvent etc.) and their concentration is selected on the basis of pre formulation studies like phase equilibrium studies, solvent capacity of oil for drug and mutual miscibility of excipients. The present review focuses mainly on the development of SEDDS and effect of excipients on oral bioavailability and aqueous solubility of poorly water soluble phytoconstituents/derived products. A recent list of patents issued for self emulsifying herbal formulation has also been included. The research data for various self emulsifying herbal formulation and patents issued was reviewed using different database such as PubMed, Google Scholar, Google patents, Scopus and Web of Science etc. In nutshell, we can say that SEDDS established as novel drug delivery system for herbals and with the advances in this technique, lots of patents on herbal SEDDS can be translated into the commercial products. PMID:25335929

Chouhan, Neeraj; Mittal, Vineet; Kaushik, Deepak; Khatkar, Anurag; Raina, Mitali

2014-10-21

302

Microneedle-based drug delivery systems for transdermal route.  

PubMed

Transdermal delivery offers an attractive, noninvasive administration route but it is limited by the skin's barrier to penetration. Minimally invasive techniques, such as the use of microneedles (MNs), bypass the stratum corneum (SC) barrier to permit the drug's direct access to the viable epidermis. These novel micro devices have been developed to puncture the skin for the transdermal delivery of hydrophilic drugs and macromolecules, including peptides, DNA and other molecules, that would otherwise have difficulty passing the outermost layer of the skin, the SC. Using the tools of the microelectronics industry, MNs have been fabricated with a range of sizes, shapes and materials. MNs have been shown to be robust enough to penetrate the skin and dramatically increase the skin permeability of several drugs. Moreover, MNs have reduced needle insertion pain and tissue trauma and provided controlled delivery across the skin. This review focuses on the current state of the art in the transdermal delivery of drugs using various types of MNs and developments in the field of microscale devices, as well as examples of their uses and clinical safety. PMID:24144208

Pierre, Maria Bernadete Riemma; Rossetti, Fabia Cristina

2014-03-01

303

Drug Delivery Into the Eye With the Use of Ultrasound  

E-print Network

was supported by the Seattle Foundation, the Center for Industrial and Medical Ultrasound, and National Eye for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 NE 40th StDrug Delivery Into the Eye With the Use of Ultrasound Vesna Zderic, PhD, John I. Clark, Ph

Clark, John

304

Trojan particles: Large porous carriers of nanoparticles for drug delivery  

Microsoft Academic Search

We have combined the drug release and delivery potential of nanoparticle (NP) systems with the ease of flow, processing, and aerosolization potential of large porous particle (LPP) systems by spray drying solutions of polymeric and nonpolymeric NPs into extremely thin-walled macroscale structures. These hybrid LPPs exhibit much better flow and aerosolization properties than the NPs; yet, unlike the LPPs, which

N. Tsapis; D. Bennett; B. Jackson; D. A. Weitz; D. A. Edwards

2002-01-01

305

Drug Design, Development, and Delivery: An Interdisciplinary Course on Pharmaceuticals  

ERIC Educational Resources Information Center

We developed a new interdisciplinary course on pharmaceuticals to address needs of undergraduate and graduate students in chemical engineering and other departments. This course introduces drug design, development, and delivery in an integrated fashion that provides scientific depth in context with broader impacts in business, policy, and ethics.…

Prausnitz, Mark R.; Bommarius, Andreas S.

2011-01-01

306

Recent advances in self-emulsifying drug delivery systems (SEDDS).  

PubMed

One of the biggest challenges confronting the contemporary drug delivery science today is to improve on the oral bioavailability of a vast number of drugs exhibiting poor and inconsistent gastrointestinal absorption. Self-emulsifying drug delivery systems (SEDDS) have been proved as highly useful technological innovations to surmount such bioavailability hiccups by virtue of their diminutive globule size, higher solubilization tendency for hydro-phobic drugs, robust formulation advantages, and easier scalability in the industrial milieu. Besides, these systems are also known to inhibit the P-glycoprotein (P-gp) efflux, reduce metabolism by gut Cytochrome P-450 enzymes, and circumnavigate the hepatic first-pass effect, facilitating absorption of drugs via intestinal lymphatic pathways. In the last two decades, the phenomenal success of SEDDS as a potential tool for oral delivery of drugs has extrapolated their applications to non-oral delivery also. Various innovative approaches and patented techniques have been reported on formulation of diverse oral and non-oral self-emulsifying (SE) systems not only of various synthetic and semisynthetic drugs, but also of several phytopharmaceuticals, nutraceuticals, and biological macromolecules. Of late, an escalating number of reports have been pouring in on special types of SE systems, mostly nanosized, employing functional excipients such as polar lipids, phospholipids, cellulosic polymer, diblock polymers, etc. This review paper provides an updated bird's-eye view account on the publications and patents of such novel SE approaches for use in both oral and non-oral therapeutics. Providing a relatively pithy overview, this paper thus endeavors to act as a repertoire of knowledge and know-how to guide the product development scientist in formulating variegated SE systems. PMID:24940626

Singh, Bhupinder; Beg, Sarwar; Khurana, Rajneet Kaur; Sandhu, Premjeet Singh; Kaur, Ravinder; Katare, Om Parkash

2014-01-01

307

Current therapies and technological advances in aqueous aerosol drug delivery.  

PubMed

Recent advances in aerosolization technology have led to renewed interest in pulmonary delivery of a variety of drugs. Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) have experienced success in recent years; however, many limitations are presented by formulation difficulties, inefficient delivery, and complex device designs. Simplification of the formulation process as well as adaptability of new devices has led many in the pharmaceutical industry to reconsider aerosolization in an aqueous carrier. In the acute care setting, breath-enhanced air-jet nebulizers are controlling and minimizing the amount of wasted medication, while producing a high percentage of respirable droplets. Vibrating mesh nebulizers offer advantages in higher respirable fractions (RFs) and slower velocity aerosols when compared with air-jet nebulizers. Vibrating mesh nebulizers incorporating formulation and patient adaptive components provide improvements to continuous nebulization technology by generating aerosol only when it is most likely to reach the deep lung. Novel innovations in generation of liquid aerosols are now being adapted for propellant-free pulmonary drug delivery to achieve unprecedented control over dose delivered and are leading the way for the adaptation of systemic drugs for delivery via the pulmonary route. Devices designed for the metered dose delivery of insulin, morphine, sildenafil, triptans, and various peptides are all currently under investigation for pulmonary delivery to treat nonrespiratory diseases. Although these devices are currently still in clinical testing (with the exception of the Respimat), metered dose liquid inhalers (MDLIs) have already shown superior outcomes to current pulmonary and systemic delivery methods. PMID:18663654

Watts, Alan B; McConville, Jason T; Williams, Robert O

2008-09-01

308

Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems.  

PubMed

For many drug candidates a modified in vivo drug release is desired to improve efficacy, sustain effect or minimise toxicity. Polymeric delivery systems, such as microspheres, nanospheres and polymeric films, have been extensively researched in an attempt to achieve modified drug release. Cyclodextrins offer an alternative approach. These cyclic oligosaccharides have the ability to form non-covalent complexes with a number of drugs and in so doing alter their physicochemical properties. In addition, the primary and secondary hydroxyl groups of the native (alpha, beta, gamma-) cyclodextrins are potential sites for chemical modification. It follows that the incorporation of these agents into polymeric drug delivery systems, as physical mixtures, covalently bound conjugates or cross-linking agents, frequently permits a greater degree of control of drug release. This paper reviews the incorporation of various cyclodextrins into polymeric formulations. The mechanisms by which cyclodextrin/polymer formulations act to modify drug release are considered. PMID:10704788

Bibby, D C; Davies, N M; Tucker, I G

2000-03-20

309

Drug Delivery to the Inner Ear  

PubMed Central

Bionic devices electrically activate neural populations to partially restore lost function. Of fundamental importance is the functional integrity of the targeted neurons. However, in many conditions the ongoing pathology can lead to continued neural degeneration and death that may compromise the effectiveness of the device and limit future strategies to improve performance. The use of drugs that can prevent nerve cell degeneration and promote their regeneration may improve clinical outcomes. In this paper we focus on strategies of delivering neuroprotective drugs to the auditory system in a way that is safe and clinically relevant for use in combination with a cochlear implant. The aim of this approach is to prevent neural degeneration and promote nerve regrowth in order to improve outcomes for cochlear implant recipients using techniques that can be translated to the clinic. PMID:23186937

Wise, Andrew K; Gillespie, Lisa N

2012-01-01

310

Polymeric micelles: authoritative aspects for drug delivery  

Microsoft Academic Search

The generation of supramolecular architectures with well-defined structures and functionalities is recently garnering attraction. Self-assemblage of amphiphilic polymers leads to the formation of polymeric micelles that demonstrate unique set of characteristics such as excellent biocompatibility, low toxicity, enhanced blood circulation time, and solubilization of poorly water-soluble drugs. In this article, we provide an up-to-date review on important aspects of polymeric

Sushant S. Kulthe; Yogesh M. Choudhari; Nazma N. Inamdar; Vishnukant Mourya

2012-01-01

311

Biodegradable nanoparticles for sustained occular drug delivery  

NASA Astrophysics Data System (ADS)

Apoptosis (programmed cell-death) is a common final pathway through which cells die in retinal degenerative diseases. The purpose of this project was to develop biodegradable nanoparticles that quickly deliver XIAP, an inhibitor of apoptosis, to retinal cells following acute insults. In vitro protein release profiles from different formulations were established, and two cell types were incubated with nanoparticles to assess cellular uptake. Subretinal injections were carried out in rats to assess in vivo localization and possible toxicity. In vitro studies showed an initial burst of protein followed by sustained release, with overall low levels of protein release. Cell culture experiments suggest that particles are mostly membrane-bound, and some may be internalized. In vivo experiments revealed no signs of toxicity, and protein localized within the photoreceptor layer. In conclusion, nanoparticles may provide a good delivery system for XIAP; however higher levels of protein release are needed for neuroprotection, warranting further investigation.

Cleroux, Carolyne

312

Electrospinning of polymeric nanofibers for drug delivery applications.  

PubMed

Electrospinning has been recognized as a simple and versatile method for fabrication of polymer nanofibers. Various polymers that include synthetic, natural, and hybrid materials have been successfully electrospun into ultrafine fibers. The inherently high surface to volume ratio of electrospun fibers can enhance cell attachment, drug loading, and mass transfer properties. Drugs ranging from antibiotics and anticancer agents to proteins, DNA, RNA, living cells, and various growth factors have been incorporated into electrospun fibers. This article presents an overview of electrospinning techniques and their application in drug delivery. PMID:24768792

Hu, Xiuli; Liu, Shi; Zhou, Guangyuan; Huang, Yubin; Xie, Zhigang; Jing, Xiabin

2014-07-10

313

A laser based reusable microjet injector for transdermal drug delivery  

NASA Astrophysics Data System (ADS)

A laser based needle-free liquid drug injection device has been developed. A laser beam is focused inside the liquid contained in the rubber chamber of microscale. The focused laser beam causes explosive bubble growth, and the sudden volume increase in a sealed chamber drives a microjet of liquid drug through the micronozzle. The exit diameter of a nozzle is 125 ?m and the injected microjet reaches an average velocity of 264 m/s. This device adds the time-varying feature of microjet to the current state of liquid injection for drug delivery.

Han, Tae-hee; Yoh, Jack J.

2010-05-01

314

Red Blood Cell Membrane-Cloaked Nanoparticles For Drug Delivery  

NASA Astrophysics Data System (ADS)

Herein we describe the development of the Red Blood Cell coated nanoparticle, RBC-NP. Purified natural erythrocyte membrane is used to coat drug-loaded poly(lacticco-glycolic acid) (PLGA). Synthetic PLGA co-polymer is biocompatible and biodegradable and has already received US FDA approval for drug-delivery and diagnostics. This work looks specifically at the retention of immunosuppressive proteins on RBC-NPs, right-sidedness of natural RBC membranes interfacing with synthetic polymer nanoparticles, sustained and retarded drug release of RBC-NPs as well as further surface modification of RBC-NPs for increased targeting of model cancer cell lines.

Carpenter, Cody Westcott

315

Advanced Materials and Processing for Drug Delivery: The Past and the Future  

PubMed Central

Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Materials innovation and nanotechnology have synergistically fueled the advancement of drug delivery. Innovation in material chemistry allows the generation of biodegradable, biocompatible, environment-responsive, and targeted delivery systems. Nanotechnology enables control over size, shape and multi-functionality of particulate drug delivery systems. In this review, we focus on the materials innovation and processing of drug delivery systems and how these advances have shaped the past and may influence the future of drug delivery. PMID:23088863

Zhang, Ying; Chan, Hon Fai; Leong, Kam W.

2012-01-01

316

pH-responsive Nanoparticles for Drug Delivery  

PubMed Central

First-generation nanoparticles (NPs) have been clinically translated as pharmaceutical drug delivery carriers for their ability to improve on drug tolerability, circulation half-life, and efficacy. Towards the development of the next-generation NPs, researchers have designed novel multifunctional platforms for sustained release, molecular targeting, and environmental responsiveness. This review focuses on environmentally-responsive mechanisms used in NP designs, and highlights the use of pH-responsive NPs in drug delivery. Different organs, tissues, and subcellular compartments – as well as their pathophysiological states – can be characterized by their pH levels and gradients. When exposed to these pH stimuli, pH-responsive NPs respond with physicochemical changes to their material structure and surface characteristics. These include swelling, dissociating or surface charge switching, in a manner that favors drug release at the target site over surrounding tissues. The novel developments described here may revise the classical outlook that NPs are passive delivery vehicles, in favor of responsive, sensing vehicles that use environmental cues to achieve maximal drug potency. PMID:20836539

Gao, Weiwei; Chan, Juliana; Farokhzad, Omid C.

2010-01-01

317

Opinion: Assessing the Barriers to Image Guided Drug Delivery  

PubMed Central

Imaging has become a cornerstone for medical diagnosis and the guidance of patient management. A new field called Image Guided Drug Delivery (IGDD) now combines the vast potential of the radiological sciences with the delivery of treatment and promises to fulfill the vision of personalized medicine. Whether imaging is used to deliver focused energy to drug-laden particles for enhanced, local drug release around tumors, or it is invoked in the context of nanoparticle-based agents to quantify distinctive biomarkers that could risk-stratify patients for improved targeted drug delivery efficiency, the overarching goal of IGDD is to use imaging to maximize effective therapy in diseased tissues and to minimize systemic drug exposure in order to reduce toxicities. Over the last several years innumerable reports and reviews covering the gamut of IGDD technologies have been published, but inadequate attention has been directed towards identifying and addressing the barriers limiting clinical translation. In this consensus opinion, the opportunities and challenges impacting the clinical realization of IGDD-based personalized medicine were discussed as a panel and recommendations were proffered to accelerate the field forward. PMID:24339356

Lanza, Gregory M.; Moonen, Chrit; Baker, James R.; Chang, Esther; Cheng, Zheng; Grodzinski, Piotr; Ferrara, Katherine; Hynynen, Kullervo; Kelloff, Gary; Koo Lee, Yong-Eun; Patri, Anil K; Sept, David; Schnitzer, Jan E.; Wood, Bradford J.; Zhang, Miqin; Zheng, Gang; Farahani, Keyvan

2014-01-01

318

Novel drug delivery approaches on antiviral and antiretroviral agents  

PubMed Central

Viruses have the property to replicate very fast in host cell. It can attack any part of host cell. Therefore, the clinical efficacy of antiviral drugs and its bioavailability is more important concern taken into account to treat viral infections. The oral and parenteral routes of drug administration have several shortcomings, however, which could lead to the search for formulating better delivery systems. Now, a day's novel drug delivery systems (NDDS) proved to be a better approach to enhance the effectiveness of the antivirals and improve the patient compliance and decrease the adverse effect. The NDDS have reduced the dosing frequency and shorten the duration of treatment, thus, which could lead the treatment more cost-effective. The development of NDDS for antiviral and antiretroviral therapy aims to deliver the drug devoid of toxicity, with high compatibility and biodegradability, targeting the drug to specific sites for viral infection and in some instances it also avoid the first pass metabolism effect. This article aims to discuss the usefulness of novel delivery approaches of antiviral agents such as niosomes, microspheres, microemulsions, nanoparticles that are used in the treatment of various Herpes viruses and in human immunodeficiency virus (HIV) infections. PMID:23057001

Sharma, Pooja; Chawla, Anuj; Arora, Sandeep; Pawar, Pravin

2012-01-01

319

Nanoparticle-Mediated Pulmonary Drug Delivery: A Review  

PubMed Central

Colloidal drug delivery systems have been extensively investigated as drug carriers for the application of different drugs via different routes of administration. Systems, such as solid lipid nanoparticles, polymeric nanoparticles and liposomes, have been investigated for a long time for the treatment of various lung diseases. The pulmonary route, owing to a noninvasive method of drug administration, for both local and systemic delivery of an active pharmaceutical ingredient (API) forms an ideal environment for APIs acting on pulmonary diseases and disorders. Additionally, this route offers many advantages, such as a high surface area with rapid absorption due to high vascularization and circumvention of the first pass effect. Aerosolization or inhalation of colloidal systems is currently being extensively studied and has huge potential for targeted drug delivery in the treatment of various diseases. Furthermore, the surfactant-associated proteins present at the interface enhance the effect of these formulations by decreasing the surface tension and allowing the maximum effect. The most challenging part of developing a colloidal system for nebulization is to maintain the critical physicochemical parameters for successful inhalation. The following review focuses on the current status of different colloidal systems available for the treatment of various lung disorders along with their characterization. Additionally, different in vitro, ex vivo and in vivo cell models developed for the testing of these systems with studies involving cell culture analysis are also discussed. PMID:24717409

Paranjpe, Mukta; Müller-Goymann, Christel C.

2014-01-01

320

Diffusion-limited binding explains binary dose response for local arterial and tumour drug delivery  

E-print Network

Background:? Local drug delivery has transformed medicine, yet it remains unclear how drug efficacy depends on physicochemical properties and delivery kinetics. Most therapies seek to prolong release, yet recent studies ...

Tzafriri, A. R.

321

RAPID AND REPEATED BOLUS DRUG DELIVERY ENABLED BY HIGH EFFICIENCY ELECTROCHEMICAL BELLOWS ACTUATORS  

E-print Network

RAPID AND REPEATED BOLUS DRUG DELIVERY ENABLED BY HIGH EFFICIENCY ELECTROCHEMICAL BELLOWS ACTUATORS of an electrolyte-filled Parylene bellows and these improved electrodes for drug delivery applications. Specifically

Meng, Ellis

322

Microsponges: A novel strategy for drug delivery system.  

PubMed

Microsponges are polymeric delivery systems composed of porous microspheres. They are tiny sponge-like spherical particles with a large porous surface. Moreover, they may enhance stability, reduce side effects and modify drug release favorably. Microsponge technology has many favorable characteristics, which make it a versatile drug delivery vehicle. Microsponge Systems are based on microscopic, polymer-based microspheres that can suspend or entrap a wide variety of substances, and can then be incorporated into a formulated product such as a gel, cream, liquid or powder. The outer surface is typically porous, allowing a sustained flow of substances out of the sphere. Microsponges are porous, polymeric microspheres that are used mostly for topical use and have recently been used for oral administration. Microsponges are designed to deliver a pharmaceutical active ingredient efficiently at the minimum dose and also to enhance stability, reduce side effects, and modify drug release. PMID:22247859

Kaity, Santanu; Maiti, Sabyasachi; Ghosh, Ashoke Kumar; Pal, Dilipkumar; Ghosh, Animesh; Banerjee, Subham

2010-07-01

323

Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer.  

PubMed

Nanoscale drug delivery systems using liposomes and nanoparticles are emerging technologies for the rational delivery of chemotherapeutic drugs in the treatment of cancer. Their use offers improved pharmacokinetic properties, controlled and sustained release of drugs and, more importantly, lower systemic toxicity. The commercial availability of liposomal Doxil and albumin-nanoparticle-based Abraxane has focused attention on this innovative and exciting field. Recent advances in liposome technology offer better treatment of multidrug-resistant cancers and lower cardiotoxicity. Nanoparticles offer increased precision in chemotherapeutic targeting of prostate cancer and new avenues for the treatment of breast cancer. Here we review current knowledge on the two technologies and their potential applications to cancer treatment. PMID:19837467

Malam, Yogeshkumar; Loizidou, Marilena; Seifalian, Alexander M

2009-11-01

324

Gelatin carriers for drug and cell delivery in tissue engineering.  

PubMed

The ability of gelatin to form complexes with different drugs has been investigated for controlled release applications. Gelatin parameters, such as crosslinking density and isoelectric point, have been tuned in order to optimize gelatin degradation and drug delivery kinetics. In recent years, focus has shifted away from the use of gelatin in isolation toward the modification of gelatin with functional groups and the fabrication of material composites with embedded gelatin carriers. In this review, we highlight some of the latest work being performed in these areas and comment on trends in the field. Specifically, we discuss gelatin modifications for immune system evasion, drug stabilization, and targeted delivery, as well as gelatin composite systems based on ceramics, naturally-occurring polymers, and synthetic polymers. PMID:24746627

Santoro, Marco; Tatara, Alexander M; Mikos, Antonios G

2014-09-28

325

Porous silicon in drug delivery devices and materials?  

PubMed Central

Porous Si exhibits a number of properties that make it an attractive material for controlled drug delivery applications: The electrochemical synthesis allows construction of tailored pore sizes and volumes that are controllable from the scale of microns to nanometers; a number of convenient chemistries exist for the modification of porous Si surfaces that can be used to control the amount, identity, and in vivo release rate of drug payloads and the resorption rate of the porous host matrix; the material can be used as a template for organic and biopolymers, to prepare composites with a designed nanostructure; and finally, the optical properties of photonic structures prepared from this material provide a self-reporting feature that can be monitored in vivo. This paper reviews the preparation, chemistry, and properties of electrochemically prepared porous Si or SiO2 hosts relevant to drug delivery applications. PMID:18508154

Anglin, Emily J.; Cheng, Lingyun; Freeman, William R.; Sailor, Michael J.

2009-01-01

326

Synthetic and bioinspired cage nanoparticles for drug delivery.  

PubMed

Nanotechnology has the potential to revolutionize drug delivery, but still faces some limitations. One of the main issues regarding conventional nanoparticles is their poor drug-loading and their early burst release. Thus, to overcome these problems, researchers have taken advantage of the host-guest interactions that drive some assemblies to form cage molecules able to strongly entrap their cargo and design new nanocarriers called cage nanoparticles. These systems can be classified into two categories: bioinspired nanosystems such as virus-like particles, ferritin, small heat shock protein: and synthetic host-guest supramolecular systems that require engineering to actually form supramolecular nanoassemblies. This review will highlight the recent advances in cage nanoparticles for drug delivery with a particular focus on their biomedical applications. PMID:25253501

Deshayes, Stephanie; Gref, Ruxandra

2014-07-01

327

Doxorubicin and paclitaxel loaded microbubbles for ultrasound triggered drug delivery  

PubMed Central

A polymer ultrasound contrast agent (UCA) developed in our lab has been shown to greatly reduce in size when exposed to ultrasound, resulting in nanoparticles less than 400 nm in diameter capable of escaping the leaky vasculature of a tumor to provide a sustained release of drug. Previous studies with the hydrophilic drug doxorubicin (DOX) demonstrated enhanced drug delivery to tumors when triggered with ultrasound. However the therapeutic potential has been limited due to the relatively low payload of DOX. This study compares the effects of loading the hydrophobic drug paclitaxel (PTX) on the agent’s acoustic properties, drug payload, tumoricidal activity, and the ability to deliver drugs through 400 nm pores. A maximum payload of 129.46 ± 1.80 ?g PTX/mg UCA (encapsulation efficiency 71.92 ± 0.99 %) was achieved, 20 times greater than the maximum payload of DOX (6.2 ?g/mg), while maintaining the acoustic properties. In vitro, the tumoricidal activity of paclitaxel loaded UCA exposed to ultrasound was significantly greater than controls not exposed to ultrasound (p<0.0016). This study has shown that PTX loaded UCA triggered with focused ultrasound have the potential to provide a targeted and sustained delivery of drug to tumors. PMID:21609756

Cochran, Michael C.; Eisenbrey, John; Ouma, Richard O.; Soulen, Michael; Wheatley, Margaret A.

2011-01-01

328

Diffusion of Macromolecules in the Brain: Implications for Drug Delivery  

PubMed Central

Therapeutics must diffuse through the brain extracellular space (ECS) in order to distribute within the central nervous system (CNS) compartment; this requirement holds both for drugs that are directly placed within the CNS (i.e. central input) and for drugs that cross the barriers separating blood and brain following systemic administration. The diffusion of any substance within the CNS may be affected by a number of properties associated with the brain microenvironment, e.g. the volume fraction, geometry, width, and local viscosity of the ECS, as well as interactions with cell surfaces, the extracellular matrix, and components of the interstitial fluid. Here, we discuss ECS properties important in governing the distribution of macromolecules (e.g. antibodies and other protein therapeutics), nanoparticles and viral vectors within the CNS. We also provide an introduction to some of the methods commonly applied to measure diffusion of molecules in the brain ECS, with a particular emphasis on those used for determining the diffusion properties of macromolecules. Finally, we discuss how quantitative diffusion measurements can be used to better understand and potentially even improve upon CNS drug delivery by modeling delivery within and across species, screening drugs and drug conjugates, evaluating methods for altering drug distribution, and appreciating important changes in drug distribution that may occur with CNS disease or injury. PMID:23298378

Wolak, Daniel J.; Thorne, Robert G.

2013-01-01

329

Floating Drug Delivery of Nevirapine as a Gastroretentive System  

PubMed Central

A multiple-unit floating drug delivery system based on gas formation technique was developed, in order to prolong the gastric residence time and to increase the overall bioavailability of the dosage form. The floating bead formulations were prepared by dispersing nevirapine together with calcium carbonate in a mixture of sodium alginate and hydroxypropyl methylcellulose solution and then dripping the dispersion into an acidified solution of calcium chloride. Calcium alginate beads were formed, as the alginate underwent ionotropic gelation by calcium ions, and carbon dioxide developed from the reaction of carbonate salts with acid. The obtained beads were able to float due to CO2-gas formation and the gas entrapment by the polymeric membrane. The prepared beads were evaluated for percent drug loading, drug entrapment efficiency, morphology, surface topography, buoyancy, in-vitro release, and release kinetics. The formulations were optimized for different weight ratios of the gas-forming agent and sodium alginate. The beads containing higher amounts of calcium carbonate demonstrated an instantaneous, complete, and excellent floating ability over a period of 24 hours. The increased amount of the gas forming agent did not affect the time to float, but increased the drug release from the floating beads, while increasing the coating level of the gas-entrapped membrane, increased the time to float, and slightly retarded the drug release. Good floating properties and sustained drug release were achieved. Finally, these floating beads seemed to be a promising gastroretentive drug delivery system. PMID:21264092

Vedha, Hari BN; Brahma, Reddy A; Samyuktha, Rani B

2010-01-01

330

Efficient Hepatic Delivery of Drugs: Novel Strategies and Their Significance  

PubMed Central

Liver is a vital organ responsible for plethora of functions including detoxification, protein synthesis, and the production of biochemicals necessary for the sustenance of life. Therefore, patients with chronic liver diseases such as viral hepatitis, liver cirrhosis, and hepatocellular carcinoma need immediate attention to sustain life and as a result are often exposed to the prolonged treatment with drugs/herbal medications. Lack of site-specific delivery of these medications to the hepatocytes/nonparenchymal cells and adverse effects associated with their off-target interactions limit their continuous use. This calls for the development and fabrication of targeted delivery systems which can deliver the drug payload at the desired site of action for defined period of time. The primary aim of drug targeting is to manipulate the whole body distribution of drugs, that is, to prevent distribution to non-target cells and concomitantly increase the drug concentration at the targeted site. Carrier molecules are designed for their selective cellular uptake, taking advantage of specific receptors or binding sites present on the surface membrane of the target cell. In this review, various aspects of liver targeting of drug molecules and herbal medications have been discussed which elucidate the importance of delivering the drugs/herbal medications at their desired site of action. PMID:24286077

Yadav, Narayan Prasad; Jain, Sanyog; Arora, Sumit

2013-01-01

331

Design and in vitro development of resorbable urologic drug delivery device  

E-print Network

Implantable, controlled release drug delivery devices offer several advantages over systemic oral administration routes and immediate drug release treatments including direct therapy to target organ, more continuous ...

Tobias, Irene S. (Irene Sophie)

2008-01-01

332

Fabrication and characterization of microfluidic probes for convection enhanced drug delivery  

Microsoft Academic Search

Convection enhanced drug delivery (CED) is a promising therapeutic method for treating diseases of the brain by enhancing the penetration of drugs. Most controlled release delivery methods rely on diffusion from a source to transport drugs throughout tissue. CED relies on direct infusion of drugs into tissue at a sufficiently high rate so that convective transport of drug is at

K. B. Neeves; C. T. Lo; C. P. Foley; W. M. Saltzman; W. L. Olbricht

2006-01-01

333

Optimal periodic control of a drug delivery system Subbarao Varigonda 1  

E-print Network

, Ronald A. Siegel 3 , Prodromos Daoutidis 4 Abstract Administration of certain drugs at a steady rate on the spatiotemporal pattern of drug administration, or drug delivery. With proper design, dosage forms can is a function of present drug concentration in the blood. For such drugs constant rate, or zero-order delivery

Georgiou, Tryphon T.

334

Novel drug delivery strategies for porphyrins and porphyrin precursors  

NASA Astrophysics Data System (ADS)

superficial lesions, such as actinic keratosis. In addition, photodynamic antimicrobial chemotherapy (PACT) is attracting increasing interest for the treatment of infection. However, delivery strategies for topical PDT and PACT are still based on application of rather simplistic cream and solution formulations, with little consideration given to thermodynamics, targeting or the physicochemical properties of the active agent. Purpose-designed dosage forms for topical delivery of aminolevulinic acid or its esters include creams containing penetration enhancers and/or iron chelators, pressure sensitive patches and bioadhesive patches. Such systems aim to enhance drug delivery across the stratum corneum and keratinised debris overlying neoplastic lesions and improve subsequent protoporphyrin IX (PpIX) production. The alternative to using porphyrin precursors is the use of pre-formed photosensitisers. However, owing to their relatively high molecular weights, conventional topical application is not appropriate. Innovative strategies, such as the use of needle-free injections and microneedle arrays, bypass the stratum corneum, enabling rapid and targeted delivery not only porphyrin precursors but also pre-formed photosensitisers. This presentation will review drug delivery work published to date in the fields of PDT and PACT. In addition, the benefits of employing the latest advances in pharmaceutical technology will be highlighted.

Morrow, D. I. J.; Donnelly, R. F.

2009-06-01

335

Biopolymeric alginate-chitosan nanoparticles as drug delivery carriers for cancer therapy.  

PubMed

Nanoparticulate drug delivery systems enhance cancer treatment by direct entry of nanometer particles into the fenestration in the vasculature of cancer cells. Nanoparticles for encapsulation of anticancer drugs are preferably prepared using natural polymers as carriers, with polysaccharides being particularly favorable. Alginate and chitosan polysaccharides have been widely used in nanoparticulate drug delivery systems because of their biodegradable, biocompatible, non-toxic and bioadhesive properties. In this review, we present an overview of drug delivery systems for cancer treatment, describe the use of biopolymeric alginate-chitosan nanoparticles for anticancer drug delivery, and discuss the important characteristics of these nanoparticles for use in drug delivery. PMID:25158565

Bhunchu, S; Rojsitthisak, P

2014-08-01

336

Nanoparticle-based targeted drug delivery  

PubMed Central

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© nanoparticle formulation that has shown efficacy in treating solid tumors, for single dose vaccination, and oral delivery of therapeutic proteins. PMID:19186176

Singh, Rajesh; Lillard, James W.

2009-01-01

337

Exosome mimetics: a novel class of drug delivery systems  

PubMed Central

The identification of extracellular phospholipid vesicles as conveyors of cellular information has created excitement in the field of drug delivery. Biological therapeutics, including short interfering RNA and recombinant proteins, are prone to degradation, have limited ability to cross biological membranes, and may elicit immune responses. Therefore, delivery systems for such drugs are under intensive investigation. Exploiting extracellular vesicles as carriers for biological therapeutics is a promising strategy to overcome these issues and to achieve efficient delivery to the cytosol of target cells. Exosomes are a well studied class of extracellular vesicles known to carry proteins and nucleic acids, making them especially suitable for such strategies. However, the considerable complexity and the related high chance of off-target effects of these carriers are major barriers for translation to the clinic. Given that it is well possible that not all components of exosomes are required for their proper functioning, an alternative strategy would be to mimic these vesicles synthetically. By assembly of liposomes harboring only crucial components of natural exosomes, functional exosome mimetics may be created. The low complexity and use of well characterized components strongly increase the pharmaceutical acceptability of such systems. However, exosomal components that would be required for the assembly of functional exosome mimetics remain to be identified. This review provides insights into the composition and functional properties of exosomes, and focuses on components which could be used to enhance the drug delivery properties of exosome mimetics. PMID:22619510

Kooijmans, Sander AA; Vader, Pieter; van Dommelen, Susan M; van Solinge, Wouter W; Schiffelers, Raymond M

2012-01-01

338

Carrier-Based Drug Delivery System for Treatment of Acne  

PubMed Central

Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376

Vyas, Amber; Kumar Sonker, Avinesh

2014-01-01

339

Intraperitoneal Injection as a Method of Psychotropic Drug Delivery in Adult Zebrafish  

E-print Network

Chapter 14 Intraperitoneal Injection as a Method of Psychotropic Drug Delivery in Adult Zebrafish technique for drug delivery. Intraperitoneal administration has been long used for big fish species as a Method of Psychotropic Drug Delivery in Adult Zebrafish 171 used as an effective administration route

Kalueff, Allan V.

340

14:125:445 -Engineering Principles of Drug Delivery Spring 2012 -Course Outline  

E-print Network

14:125:445 - Engineering Principles of Drug Delivery Spring 2012 - Course Outline Instructor/mechanically'. The importance of intermolecular and interfacial interactions on drug delivery carriers is the focal point of this course. Topics include: drug delivery mechanisms (passive, targeted); therapeutic modalities

Muzzio, Fernando J.

341

Self-Assembled Lipid Polymer Hybrid Nanoparticles: A Robust Drug Delivery  

E-print Network

Self-Assembled Lipid Polymer Hybrid Nanoparticles: A Robust Drug Delivery Platform Liangfang Zhang of drug concentration, and be further functionalized with target- ing ligands for differential delivery.7 molecules. Liposomes have been widely used as drug delivery vehicles because of fa- vorable safety profile

Zhang, Liangfang

342

Assemblage of novel release modules for the development of adaptable drug delivery systems  

E-print Network

Assemblage of novel release modules for the development of adaptable drug delivery systems Elena. The presence of the convex and concave bases in the swellable matrix slightly changed the overall drug delivery reserved. Keywords: Matrix; Release module; Swelling; Drug delivery system; Assemblage 1. Introduction

Peppas, Nicholas A.

343

A Passive Refillable Intraocular MEMS Drug Delivery Device Ronalee Lo1  

E-print Network

A Passive Refillable Intraocular MEMS Drug Delivery Device Ronalee Lo1 , Kenrick Kuwahara1 , Po that are irreversibly bonded without the use of any adhesives. These layers form an integrated drug delivery device implantation surgery and is capable of repeated delivery of multiple drugs. Characterization of the refillable

Meng, Ellis

344

Dynamic Feedback and the Design of Closed-loop Drug Delivery Systems  

E-print Network

Dynamic Feedback and the Design of Closed-loop Drug Delivery Systems John Milton1,2 , Sue Ann´eal, Montr´eal, Canada Abstract A closed-loop drug delivery system is constructed in which external negative. The advantage of this paradigm for drug delivery is that both the steady states and stability of the multiple

Campbell, Sue Ann

345

Characterizing permeability and stability of microcapsules for controlled drug delivery by dynamic NMR microscopy  

E-print Network

Characterizing permeability and stability of microcapsules for controlled drug delivery by dynamic allow us to determine the suitability of different capsules for controlled drug delivery. As a measure but dissolve under simulated colonic condi- tions, as required for targeted drug delivery. Depending

Suter, Dieter

346

Molecular Analysis of Drug Delivery Systems Controlled by Dissolution of the Polymer Carrier  

E-print Network

Molecular Analysis of Drug Delivery Systems Controlled by Dissolution of the Polymer Carrier BALAJI NARASIMHAN AND NIKOLAOS A. PEPPASX Received September 4, 1996, from the Biomaterials and Drug Delivery-controlled drug delivery systems are characterized by a phase erosion of the polymer carrier that is associated

Peppas, Nicholas A.

347

Utah-Inha Joint Research Center on Drug Delivery Systems & Advanced Therapeutics  

E-print Network

Utah-Inha Joint Research Center on Drug Delivery Systems & Advanced Therapeutics Inha University Hospital http://www.unidds.com MISSION AND VISION: The Utah-Inha Joint Research Center on Drug Delivery therapeutics, controlled release, and targeted drug delivery from University of Utah's Department

Tipple, Brett

348

Physiology and Pharmacology A Microparticle/Hydrogel Combination Drug-Delivery  

E-print Network

Physiology and Pharmacology A Microparticle/Hydrogel Combination Drug-Delivery System for Sustained. To design and develop a drug-delivery system containing a combination of poly-loaded delivery combination. Intravitreal injection of just 2% of the systemic dose of drug-loaded microparticles

Palczewski, Krzysztof

349

A Universal Level Converter Towards the Realization of Energy Efficient Implantable Drug Delivery  

E-print Network

A Universal Level Converter Towards the Realization of Energy Efficient Implantable Drug Delivery- tem the DDNEMS (Drug Delivery Nano-Electro-Mechanical- System) should have low power dissipation converter with a 82fF capacitive load is 5µW. Keywords Drug Delivery Nano-Electro-Mechanical-Systems (DDNEMS

Mohanty, Saraju P.

350

LAdvanced Drug Delivery Reviews 46 (2001) 326 www.elsevier.com/locate/drugdeliv  

E-print Network

LAdvanced Drug Delivery Reviews 46 (2001) 3­26 www.elsevier.com/locate/drugdeliv Experimental Drug Delivery Reviews 23 (1997) 3­25. *Corresponding author. Tel.: 11-860-4413561. E-mail address rights reserved PII: S0169-409X(00)00129-0 #12;4 C.A. Lipinski et al. / Advanced Drug Delivery Reviews 46

Gates, Kent. S.

351

Selective delivery of an anticancer drug with aptamer-functionalized liposomes to breast  

E-print Network

Selective delivery of an anticancer drug with aptamer-functionalized liposomes to breast cancer, their effectiveness has rarely been established in vivo. Here we report the development of a liposomal drug delivery overexpressed on MCF-7 cell surface, and therefore enable drug delivery with high specificity. Introduction

Cheng, Jianjun

352

Drug delivery systems based on sugar-macromolecule conjugates Benjamin G Davis* & Mark A Robinson  

E-print Network

Drug delivery systems based on sugar-macromolecule conjugates Benjamin G Davis* & Mark A Robinson-tuning of active drug delivery through their great ability to undergo site- specific modification], the potential of using carbohydrates to create a truly targeted (or actively-targeted) drug delivery system has

Davis, Ben G.

353

Pharmacytes: an ideal vehicle for targeted drug delivery.  

PubMed

An ideal nanotechnology-based drug delivery system is a pharmacyte--a self-powered, computer-controlled medical nanorobot system capable of digitally precise transport, timing, and targeted delivery of pharmaceutical agents to specific cellular and intracellular destinations within the human body. Pharmacytes may be constructed using future molecular manufacturing technologies such as diamond mechanosynthesis which are currently being investigated theoretically using quantum ab initio and density-functional computational methods. Pharmacytes will have many applications in nanomedicine such as initiation of apoptosis in cancer cells and direct control of cell signaling processes. PMID:17048481

Freitas, Robert A

2006-01-01

354

Cell-Specific Aptamer-Mediated Targeted Drug Delivery  

PubMed Central

Nucleic acid aptamers are in vitro-selected small, single-stranded DNA or RNA oligonucleotides that can specifically recognize their target on the basis of their unique 3-dimensional structures. Recent advances in the development of escort aptamers to deliver and enhance the efficacy of other therapeutic agents have drawn enthusiasm in exploiting cell-type-specific aptamers as drug delivery vehicles. This review mainly focuses on the recent developments of aptamer-mediated targeted delivery systems. We also place particular emphasis on aptamers evolved against cell membrane receptors and possibilities for translation to clinical applications. PMID:21182455

Zhou, Jiehua

2011-01-01

355

Polymer- and liposome-based nanoparticles in targeted drug delivery.  

PubMed

This review focuses on polymer- and liposome-based nanoparticles used in targeted delivery of bioactive molecules, from drugs to siRNA to pDNA. The perspective centers around commercial and clinical successes, and a rationalization of these successes. Microparticulate systems are not covered, and only those applications that truly utilize the advantages of nano size are covered. "Stealth" systems dominate in this review, as most of the clinical successes are for passive targeting rather than for active targeting of tissue. The relevance of nano size to gene delivery is also discussed with relevant examples. PMID:20515826

Venkatraman, Subbu S; Ma, Lwin Lwin; Natarajan, Jayaganesh V; Chattopadhyay, Sujay

2010-01-01

356

Nanoparticles: Emerging carriers for drug delivery  

PubMed Central

The core objective of nanoparticles is to control and manipulate biomacromolecular constructs and supramolecular assemblies that are critical to living cells in order to improve the quality of human health. By definition, these constructs and assemblies are nanoscale and include entities such as drugs, proteins, DNA/RNA, viruses, cellular lipid bilayers, cellular receptor sites and antibody variable regions critical for immunology and are involved in events of nanoscale proportions. The emergence of such nanotherapeutics/diagnostics will allow a deeper understanding of human longevity and human ills that include cancer, cardiovascular disease and genetic disorders. A technology platform that provides a wide range of synthetic nanostructures that may be controlled as a function of size, shape and surface chemistry and scale to these nanotechnical dimensions will be a critical first step in developing appropriate tools and a scientific basis for understanding nanoparticles. PMID:23960751

Mudshinge, Sagar R.; Deore, Amol B.; Patil, Sachin; Bhalgat, Chetan M.

2011-01-01

357

A Pillararene-Based Ternary Drug-Delivery System with Photocontrolled Anticancer Drug Release.  

PubMed

A novel ternary drug delivery system (DDS) is constructed using a photodegradable anticancer prodrug (Py-Cbl), a water-soluble pillararene supramolecular container (WP6), and the diblock copolymer methoxy-poly(ethylene glycol)114 -block-poly(L -lysine hydrochloride)200 . This DDS successfully addresses three important issues: enhancement of the water solubility of the anticancer prodrug; controlled release of the anticancer drug; accurate and quantitative measurement of the drug release. PMID:25318658

Yu, Guocan; Yu, Wei; Mao, Zhengwei; Gao, Changyou; Huang, Feihe

2014-10-15

358

Trends in translational medicine and drug targeting and delivery: new insights on an old concept-targeted drug delivery with antibody-drug conjugates for cancers.  

PubMed

According to the JPS Drug Delivery Clinical Trials Database (jpharmscidatabase.org), 37,738, 14,104, and 8060 clinical trials are registered to evaluate (1) drug delivery technology, (2) biomolecule platform, and (3) drug metabolism and pharmacokinetic (PK)-pharmacodynamic (PD) interactions. These numbers represent a 19%-29% increase since 2012. Within biomolecules in clinical testing, antibodies constitute the majority and approximately 6% carry drug conjugates. Paul Ehrlich introduced the antibody-drug conjugate or "magic bullet" concept about a century ago. A monoclonal antibody (mAb)-drug conjugate Mylotarg was licensed for treating cancer in 2000 and exhibits significant liver toxicity and immune hypersensitivity. Plasma drug instability and a bacterial-derived drug may be partly to blame. Progress in antibody-drug conjugation chemistry, understanding how biologic systems respond to antibody-drug conjugates, and unwavering efforts of scientists have enabled successful development of highly potent and effective second-generation antibody-drug conjugates. With the approval of Adcetris for lymphoma in 2011 and Kadcyla in 2013, about a twofold to fourfold gain in cancer response rate is attributed to drug conjugates. With a demonstrated higher safety profile, many more antibody-drug conjugates are in development. The clinical success of Adcetris and Kadcyla has raised hope that antibody-guided "drug bullets" may be truly "magical" in leading to a cure for cancer. PMID:24186148

Ho, Rodney J Y; Chien, Jenny

2014-01-01

359

Multi-access drug delivery network and stability  

PubMed Central

A novel design of a multi-drug delivery network and diagnosis using a molecular network is proposed. By using a pair of tweezers to generate the intense optical vortices within the PANDA ring resonator, the required molecules (drug volumes) can be trapped and moved dynamically within the molecular bus networks, in which the required drug delivery targets can be achieved within the network. The advantage of the proposed system is that the diagnostic method can be used within a tiny system (thin film device or circuit), which is available as an embedded device for diagnostic use in patients. In practice, the large molecular networks such as ring, star, and bus networks can be integrated to form a large drug delivery system. The channel spacing of the trapped volumes (molecules) within the bus molecular networks can be provided by using the appropriate free spectrum range, which is analyzed and discussed in the terms of crosstalk effects. In this work, crosstalk effects of about 0.1% are noted, which can be neglected and does not affect the network stability. PMID:21980238

Mitatha, S; Moongfangklang, N; Jalil, MA; Suwanpayak, N; Ali, J; Yupapin, PP

2011-01-01

360

Advances in drug delivery via electrospun and electrosprayed nanomaterials  

PubMed Central

Electrohydrodynamic (EHD) techniques refer to procedures that utilize electrostatic forces to fabricate fibers or particles of different shapes with sizes in the nano-range to a few microns through electrically charged fluid jet. Employing different techniques, such as blending, surface modification, and coaxial process, there is a great possibility of incorporating bioactive such molecules as drugs, DNA, and growth factors into the nanostructures fabricated via EHD techniques. By careful selection of materials and processing conditions, desired encapsulation efficiency as well as preserved bioactivity of the therapeutic agents can be achieved. The drug-loaded nanostructures produced can be applied via different routes, such as implantation, injection, and topical or oral administration for a wide range of disease treatment. Taking advantage of the recent developments in EHD techniques like the coaxial process or multilayered structures, individually controlled delivery of multiple drugs is achievable, which is of great demand in cancer therapy and growth-factor delivery. This review summarizes the most recent techniques and postmodification methods to fabricate electrospun nanofibers and electrosprayed particles for drug-delivery applications. PMID:23976851

Zamani, Maedeh; Prabhakaran, Molamma P; Ramakrishna, Seeram

2013-01-01

361

Crosslinked Multilamellar Liposomes for Controlled Delivery of Anticancer Drugs  

PubMed Central

Liposomes constitute one of the most popular nanocarriers for the delivery of cancer therapeutics. However, since their potency is limited by incomplete drug release and inherent instability in the presence of serum components, their poor delivery occurs in certain circumstances. In this study, we address these shortcomings and demonstrate an alternative liposomal formulation, termed crosslinked multilamellar liposome (CML). With its properties of improved sustainable drug release kinetics and enhanced vesicle stability, CML can achieve controlled delivery of cancer therapeutics. CML stably encapsulated the anticancer drug doxorubicin (Dox) in the vesicle and exhibited a remarkably controlled rate of release compared to that of the unilamellar liposome (UL) with the same lipid composition or Doxil-like liposome (DLL). Our imaging study demonstrated that the CMLs were mainly internalized through a caveolin-dependent pathway and were further trafficked through the endosome-lysosome compartments. Furthermore, in vivo experiments showed that the CML-Dox formulation reduced systemic toxicity and significantly improved therapeutic activity in inhibiting tumor growth compared to that of UL-Dox or DLL-Dox. This drug packaging technology may therefore provide a new treatment option to better manage cancer and other diseases. PMID:23375392

Joo, Kye-Il; Xiao, Liang; Liu, Shuanglong; Liu, Yarong; Lee, Chi-Lin; Conti, Peter S.; Wong, Michael K.; Li, Zibo; Wang, Pin

2014-01-01

362

Colon-specific drug delivery for mebeverine hydrochloride.  

PubMed

Mebeverine Hydrochloride (MB-HCl), an effective spasmolytic drug, was formulated as CODES. A colon-specific drug delivery technology CODES was designed to avoid the inherent problems associated with pH- or time-dependent systems. To achieve more protection and control of drug release, MB-HCl was prepared as microspheres and compressed as core tablets of CODES (modified CODES). The core tablets contained the drug either in free form [Formula 1 (F(1))], or as microspheres with 2 different polymer:drug:lactulose ratios (1:1:0.5 [Formula 2 (F(2))] and 2:1:0.5 [Formula 3 (F(3))]. The release profiles of the coated CODES systems were compared with uncoated compressed tablets. The uncoated tablet showed a drug release of 94% after 1 h in simulated gastric condition (pH = 1.2). The release characteristics of the coated systems revealed that the enteric coating (Eudragit L(100)) prevented any drug release in simulated gastric or duodenal conditions in the first 3 h (pH 1.2-6.1), after which drug was slightly liberated in simulated intestinal fluid (pH 7.4) {Phase 1 (P1)}. After 4 h the pH was adjusted to 7 and beta-glucose-oxidase was added, which is an enzyme produced by enterobacteria present in the colon. The acid-soluble coat (Eudragit)E(100)) dissolved and the drug release suddenly increased to reach 95, 72 and 60.4% for F(1)-F(3), respectively. IR spectrum study showed a covalent bond between the drug and the polymer in the formulae F(2) and F(3) resulting in the sustained drug release from the microspheres with a significant difference (p>0.05) to F(1). The findings were confirmed by in vivo investigation using X-ray images for Guinea pigs ingested tablets containing barium sulphate (F(4)), where the tablet began to disintegrate after 10 h of tablet intake. The results of the study indicated that MB-HCl CODES colon-specific drug delivery can act as a successful trigger for drug targeting in the colon. Furthermore, a sustained release of the drug can be achieved from modified CODES containing the drug in the form of microspheres. PMID:18041637

Omar, Samia; Aldosari, Basmah; Refai, Hanan; Gohary, Omaimah Al

2007-12-01

363

A novel liquefied gas based oral controlled release drug delivery system for liquid drug formulations.  

PubMed

A novel liquefied gas based drug delivery system for the oral delivery of liquid and semi-solid drug formulations is presented. The capsule-shaped system is equipped with a capillary as an element controlling the release rate. The delivery mechanism is based on a constant vapor pressure produced by isopentane as a low-boiling liquefied gas. The liquid drug valproic acid (VA) was used as a model compound. The viscosity was increased by the addition of povidone (PVP). The VA-PVP gel exhibited pseudoplastic rheological properties, the shear rate was above 0.1s(-1), similar to a Newtonian liquid. The gels tested in the gas based delivery system provided near-zero-order release kinetics. The longest delivery time was up to ca. 8h. The system is characterized by high flexibility of the delivery rate, which can be achieved by adjusting system parameters such as the diameter and length of the capillary, the vapor pressure of the propellant and the viscosity of the drug formulation. PMID:22426133

Haznar-Garbacz, Dorota; Garbacz, Grzegorz; Eisenächer, Friederike; Klein, Sandra; Weitschies, Werner

2012-06-01

364

In vivo real-time monitoring system of electroporation mediated control of transdermal and topical drug delivery  

E-print Network

drug delivery Tanja Blagus a , Bostjan Markelc a , Maja Cemazar a,b , Tina Kosjek c , Veronique Preat d 39, SI-1000 Ljubljana, Slovenia d Louvain Drug Research Institute, Pharmaceutics and Drug Delivery online 7 October 2013 Keywords: Electroporation Transdermal drug delivery Topical drug delivery Multi

Ljubljana, University of

365

Multistage Nanovectors Enhance the Delivery of Free and Encapsulated Drugs.  

PubMed

Nanoparticles have considerable potential for cancer imaging and therapy due to their small size and prolonged circulation. However, biological barriers can impede the delivery of a sufficient dose of a drug to the target site, thereby also resulting in the accumulation of toxic compounds within healthy tissues, and systemic toxicity. Multistage nanovectors (MSV) preferentially accumulate on inflamed endothelium, and can thus serve as carriers for drugs and nanoparticles. Herein, we describe the loading of free (i.e., melittin) and nano-encapsulated (i.e., doxorubicin-loaded micelles) drugs into MSV, and report the impact of surface charge and pore size on drug loading. For both drug formulations, negatively charged MSV (i.e., oxidized) with larger pores were shown to retain higher concentrations of payloads compared to positively charged (i.e., APTES-modified) MSV with small pores. Treatment of human umbilical vein endothelial cells (HUVEC) with melittin-loaded MSV (MEL@MSV) resulted in an 80% reduction in cell viability after 3 days. Furthermore, MEL@MSV conjugated with anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibodies displayed preferential targeting and delivery of MEL to activated HUVEC expressing VEGFR2. Treatment of HUVEC and MCF7 cells with doxorubicin-loaded micelles (DOXNP@MSV) resulted in a 23% and 47% reduction in cell viability, respectively. Taken together, these results demonstrate increased loading of a payload in oxidized, large pore MSV, and effective delivery of free and nano-encapsulated drugs to endothelial and cancer cells. PMID:25316273

Martinez, Jonathan O; Evangelopoulos, Michael; Bhavane, Rohan; Acciardo, Stefania; Salvatore, Francesco; Liu, Xuewu; Ferrari, Mauro; Tasciotti, Ennio

2014-10-15

366

Application of Ultrasound Energy as a New Drug Delivery System  

NASA Astrophysics Data System (ADS)

Ultrasound has been in use for the last three decades as amodality for diagnostic imaging in medicine. Recently, there have beennumerous reports on the application of nonthermal ultrasound energyfor targeting or controlling drug release. This new concept oftherapeutic ultrasound combined with drugs has led to much excitementin various medical fields. Ultrasound energy can enhance the effectsof thrombolytic agents such as urokinase. Therapeutic ultrasoundcatheters are currently being developed for treatment ofcardiovascular diseases. Devices with ultrasound transducers implantedin transdermal drug patches are also being evaluated for possibledelivery of insulin through the skin. Chemical activation of drugs byultrasound energy for treatment of cancers is another new fieldrecently termed “Sonodynamic Therapy”. Various examples of ultrasoundapplication are under investigation which could lead to revolutionarydrug delivery systems in the future.

Tachibana, Katsuro; Tachibana, Shunro

1999-05-01

367

Magnetic Nanoparticles for Multi-Imaging and Drug Delivery  

PubMed Central

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. PMID:23579479

Lee, Jae-Hyun; Kim, Ji-wook; Cheon, Jinwoo

2013-01-01

368

Cyclodextrin containing biodegradable particles: from preparation to drug delivery applications.  

PubMed

Cyclodextrins (CDs) offer a very broad spectrum of applications in diverse fields of drug delivery. They are a family of cyclic ?-(1-4)-linked oligosaccharides of ?-d-glucopyranose subunits forming a more hydrophobic central cavity and a hydrophilic outer shell. CDs bear cage like supramolecular structures, similar to calixarenes, cyclophanes and crown ethers. No covalent bonds are required to host a guest molecule in the central cavity. The aim of this review is to throw light on some of the applications and formulation techniques for the novel multifunctional CD based nanocarriers used in diverse areas of drug delivery. Furthermore, this article highlights the molecular structure, chemical, complexation properties and the use of CDs in nanosystems like liposomes, magnetic nanoparticles, biodegradable polymers, micro and nanospheres and capsules. PMID:24342710

Zafar, Nadiah; Fessi, Hatem; Elaissari, Abdelhamid

2014-01-30

369

Kinetic limitations of cooperativity based drug delivery systems  

E-print Network

We study theoretically a novel drug delivery system that utilizes the overexpression of certain proteins in cancerous cells for cell specific chemotherapy. The system consists of dendrimers conjugated with "keys" (ex: folic acid) which "key-lock" bind to particular cell membrane proteins (ex: folate receptor). The increased concentration of "locks" on the surface leads to a longer residence time for the dendrimer and greater incorporation into the cell. Cooperative binding of the nanocomplexes leads to an enhancement of cell specificity. However, both our theory and detailed analysis of in-vitro experiments indicate that the degree of cooperativity is kinetically limited. We demonstrate that cooperativity and hence the specificity to particular cell type can be increased by making the strength of individual bonds weaker, and suggest a particular implementation of this idea. The implications of the work for optimizing the design of drug delivery vehicles are discussed.

Nicholas A. Licata; Alexei V. Tkachenko

2007-08-17

370

Bioavailability of capsaicin and its implications for drug delivery.  

PubMed

The dietary compound capsaicin is responsible for the "hot and spicy" taste of chili peppers and pepper extracts. It is a valuable pharmacological agent with several therapeutic applications in controlling pain and inflammation. Emerging studies show that it displays potent anti-tumor activity in several human cancers. On a more basic research level, capsaicin has been used as a ligand to activate several types of ion-channel receptors. The pharmacological activity of capsaicin-like compounds is dependent on several factors like the dose, the route of administration and most importantly on its concentration at target tissues. The present review describes the current knowledge involving the metabolism and bioavailability of capsaicinoids in rodents and humans. Novel drug delivery strategies used to improve the bioavailability and therapeutic index of capsaicin are discussed in detail. The generation of novel capsaicin-mimetics and improved drug delivery methods will foster the hope of innovative applications of capsaicin in human disease. PMID:25307998

Rollyson, William D; Stover, Cody A; Brown, Kathleen C; Perry, Haley E; Stevenson, Cathryn D; McNees, Christopher A; Ball, John G; Valentovic, Monica A; Dasgupta, Piyali

2014-12-28

371

Porous Hydroxyapatite Bioceramic Scaffolds for Drug Delivery and Bone Regeneration  

NASA Astrophysics Data System (ADS)

The conventional methods of supplying a patient with pharmacologic active substances suffer from being very poorly selective, so that damage can occurs to the healthy tissues and organs, different from the intended target. In addition, high drug doses can be required to achieve the desired effect. An alternative approach is based on the use of implantable delivery tools, able to release the active substance in a controlled way. In the current research local drug delivery devices containing 8mg of gentamicin sulphate were prepared using custom developed vacuum impregnation technique. In vitro dissolution tests showed that gentamicin release was sustained for 12h. In order to decrease gentamicin release rate, biopolymer coatings were applied and coating structure investigated. The results showed that gentamicin release can be sustained for more than 70h for poly(epsilon-caprolactone) coated calcium phosphate scaffolds. From poly lactic acid and polyvinyl alcohol coated scaffolds gentamicin was released within 20h and 50h, respectively.

Loca, Dagnija; Locs, Janis; Salma, Kristine; Gulbis, Juris; Salma, Ilze; Berzina-Cimdina, Liga

2011-10-01

372

Biocompatible polymeric implants for controlled drug delivery produced by MAPLE  

NASA Astrophysics Data System (ADS)

Implants consisting of drug cores coated with polymeric films were developed for delivering drugs in a controlled manner. The polymeric films were produced using matrix assisted pulsed laser evaporation (MAPLE) and consist of poly(lactide-co-glycolide) (PLGA), used individually as well as blended with polyethylene glycol (PEG). Indomethacin (INC) was used as model drug. The implants were tested in vitro (i.e. in conditions similar with those encountered inside the body), for predicting their behavior after implantation at the site of action. To this end, they were immersed in physiological media (i.e. phosphate buffered saline PBS pH 7.4 and blood). At various intervals of PBS immersion (and respectively in blood), the polymeric films coating the drug cores were studied in terms of morphology, chemistry, wettability and blood compatibility. PEG:PLGA film exhibited superior properties as compared to PLGA film, the corresponding implant being thus more suitable for internal use in the human body. In addition, the implant containing PEG:PLGA film provided an efficient and sustained release of the drug. The kinetics of the drug release was consistent with a diffusion mediated mechanism (as revealed by fitting the data with Higuchi's model); the drug was gradually released through the pores formed during PBS immersion. In contrast, the implant containing PLGA film showed poor drug delivery rates and mechanical failure. In this case, fitting the data with Hixson-Crowell model indicated a release mechanism dominated by polymer erosion.

Paun, Irina Alexandra; Moldovan, Antoniu; Luculescu, Catalin Romeo; Dinescu, Maria

2011-10-01

373

Transdermal Delivery Devices: Fabrication, Mechanics and Drug Release from Silk**  

PubMed Central

Microneedles are a relatively simple, minimally invasive and painless approach to deliver drugs across the skin. However, there remain limitations with this approach because of the materials most commonly utilized for such systems. Silk protein, with tunable and biocompatibility properties, is a useful biomaterial to overcome the current limitations with microneedles. Silk devices preserve drug activity, offer superior mechanical properties and biocompatibility, can be tuned for biodegradability, and can be processed under aqueous, benign conditions. In the present work, we report the fabrication of dense microneedle arrays from silk with different drug release kinetics. The mechanical properties of the microneedle patches are tuned by post-fabrication treatments or by loading the needles with silk microparticles to increase capacity and mechanical strength. Drug release is further enhanced by the encapsulation of the drugs in the silk matrix and coating with a thin dissolvable drug layer. The microneedles are used on human cadaver skin and drugs were delivered successfully. The various attributes demonstrated suggest that silk-based microneedle devices can provide significant benefit as a platform material for transdermal drug delivery. PMID:23653252

Raja, Waseem K.; MacCorkle, Scott; Diwan, Izzuddin M.; Abdurrob, Abdurrahman; Lu, Jessica; Omenetto, Fiorenzo G.; Kaplan, David L.

2013-01-01

374

Multifunctional Inorganic Nanoparticles for Imaging, Targeting, and Drug Delivery  

PubMed Central

Drug delivery, magnetic resonance and fluorescence imaging, magnetic manipulation, and cell targeting are simultaneously possible using a multifunctional mesoporous silica nanoparticle. Superparamagnetic iron oxide nanocrystals were encapsulated inside mesostructured silica spheres that were labeled with fluorescent dye molecules and coated with hydrophilic groups to prevent aggregation. Water-insoluble anticancer drugs were delivered into human cancer cells; surface conjugation with cancer-specific targeting agents increased the uptake into cancer cells relative to that in non-cancerous fibroblasts. The highly versatile multifunctional nanoparticles could potentially be used for simultaneous imaging and therapeutic applications. PMID:19206485

Liong, Monty; Lu, Jie; Kovochich, Michael; Xia, Tian; Ruehm, Stefan G.; Nel, Andre E.; Tamanoi, Fuyuhiko; Zink, Jeffrey I.

2009-01-01

375

Recent Applications of Mesoscale Modeling to Nanotechnology and Drug Delivery  

SciTech Connect

Mesoscale simulations have traditionally been used to investigate structural morphology of polymer in solution, melts and blends. Recently we have been pushing such modeling methods to important areas of Nanotechnology and Drug delivery that are well out of reach of classical molecular dynamics. This paper summarizes our efforts in three important emerging areas: (1) polymer-nanotube composites; (2) drug diffusivity through cell membranes; and (3) solvent exchange in nanoporous membranes. The first two applications are based on a bead-spring-based approach as encoded in the Dissipative Particle Dynamics (DPD) module. The last application used density-based Mesoscale modeling as implemented in the Mesodyn module.

Maiti, A; Wescott, J; Kung, P; Goldbeck-Wood, G

2005-02-11

376

Engineered spider silk protein-based composites for drug delivery.  

PubMed

Silk protein-based materials are promising materials for the delivery of drugs and other active ingredients, due to their processability, biocompatibility, and biodegradability. The preparation of films composed of an engineered spider silk protein (eADF4(C16)) in combination with either a polyester (polycaprolactone) or a polyurethane (pellethane), and their physical properties are described. The release profiles are affected by both the film composition and the presence of enzymes, and release can be observed over a period of several weeks. Such silk-based composites have potential as drug eluting biocompatible coatings or implantable devices. PMID:23881554

Hardy, John G; Leal-Egaña, Aldo; Scheibel, Thomas R

2013-10-01

377

Novel biomimetic polymersomes as polymer therapeutics for drug delivery  

Microsoft Academic Search

Novel amphiphilic diblock copolymers, cholesterol-end-capped poly(2-methacryloyloxyethyl phosphorylcholine) (CMPC), which have poly(2-methacryloyloxyethyl phosphorylcholine) (poly(MPC)) as hydrophilic segment and cholesterol as hydrophobic segment, was specially designed as drug delivery systems. Fluorescence probe technique and transmission electron microscope (TEM) characterizations indicated that this novel amphiphilic copolymer formed micelles structure in water and the critical micelle concentration (CMC) was determined to be 1.57×10?7 mol\\/l.

Jian-Ping Xu; Jian Ji; Wei-Dong Chen; Jia-Cong Shen

2005-01-01

378

Electrohydrodynamics: A facile technique to fabricate drug delivery systems  

Microsoft Academic Search

Electrospinning and electrospraying are facile electrohydrodynamic fabrication methods that can generate drug delivery systems (DDS) through a one-step process. The nanostructured fiber and particle morphologies produced by these techniques offer tunable release kinetics applicable to diverse biomedical applications. Coaxial electrospinning\\/electrospraying, a relatively new technique of fabricating core–shell fibers\\/particles have added to the versatility of these DDS by affording a near

Syandan Chakraborty; I-Chien Liao; Andrew Adler; Kam W. Leong

2009-01-01

379

MEMS-based micropumps in drug delivery and biomedical applications  

Microsoft Academic Search

This paper briefly overviews progress on the development of MEMS-based micropumps and their applications in drug delivery and other biomedical applications such as micrototal analysis systems (?TAS) or lab-on-a-chip and point of care testing systems (POCT). The focus of the review is to present key features of micropumps such as actuation methods, working principles, construction, fabrication methods, performance parameters and

A. Nisar; Nitin Afzulpurkar; Banchong Mahaisavariya; Adisorn Tuantranont

2008-01-01

380

Breakthrough discoveries in drug delivery technologies: the next 30 years.  

PubMed

What if we could open the 2044 special issue of the Journal of Controlled Release? Which drug delivery technologies will have led the field? Which ones will have successfully reached the marketplace? In attempting to answer these questions, we selected a few recent technologies and concepts that could, in our opinion, play a crucial role in coming years. In each case, emblematic papers are cited to introduce and discuss the selected topic. PMID:24794899

Brambilla, Davide; Luciani, Paola; Leroux, Jean-Christophe

2014-09-28

381

Engineering and evaluating drug delivery particles in microfluidic devices.  

PubMed

The development of new and improved particle-based drug delivery is underpinned by an enhanced ability to engineer particles with high fidelity and integrity, as well as increased knowledge of their biological performance. Microfluidics can facilitate these processes through the engineering of spatiotemporally highly controlled environments using designed microstructures in combination with physical phenomena present at the microscale. In this review, we discuss microfluidics in the context of addressing key challenges in particle-based drug delivery. We provide an overview of how microfluidic devices can: (i) be employed to engineer particles, by providing highly controlled interfaces, and (ii) be used to establish dynamic in vitro models that mimic in vivo environments for studying the biological behavior of engineered particles. Finally, we discuss how the flexible and modular nature of microfluidic devices provides opportunities to create increasingly realistic models of the in vivo milieu (including multi-cell, multi-tissue and even multi-organ devices), and how ongoing developments toward commercialization of microfluidic tools are opening up new opportunities for the engineering and evaluation of drug delivery particles. PMID:24794898

Björnmalm, Mattias; Yan, Yan; Caruso, Frank

2014-09-28

382

Overcoming cellular and tissue barriers to improve liposomal drug delivery  

NASA Astrophysics Data System (ADS)

Forty years of liposome research have demonstrated that the anti-tumor efficacy of liposomal therapies is, in part, driven by three parameters: 1) liposome formulation and lipid biophysics, 2) accumulation and distribution in the tumor, and 3) release of the payload at the site of interest. This thesis outlines three studies that improve on each of these delivery steps. In the first study, we engineer a novel class of zwitterlipids with an inverted headgroup architecture that have remarkable biophysical properties and may be useful for drug delivery applications. After intravenous administration, liposomes accumulate in the tumor by the enhanced permeability and retention effect. However, the tumor stroma often limits liposome efficacy by preventing distribution into the tumor. In the second study, we demonstrate that depletion of hyaluronan in the tumor stroma improves the distribution and efficacy of DoxilRTM in murine 4T1 tumors. Once a liposome has distributed to the therapeutic site, it must release its payload over the correct timescale. Few facile methods exist to quantify the release of liposome therapeutics in vivo. In the third study, we outline and validate a simple, robust, and quantitative method for tracking the rate and extent of release of liposome contents in vivo. This tool should facilitate a better understanding of the pharmacodynamics of liposome-encapsulated drugs in animals. This work highlights aspects of liposome behavior that have prevented successful clinical translation and proposes alternative approaches to improve liposome drug delivery.

Kohli, Aditya G.

383

Polyphosphazenes: Multifunctional, Biodegradable Vehicles for Drug and Gene Delivery  

PubMed Central

Poly[(organo)phosphazenes] are a unique class of extremely versatile polymers with a range of applications including tissue engineering and drug delivery, as hydrogels, shape memory polymers and as stimuli responsive materials. This review aims to divulge the basic principles of designing polyphosphazenes for drug and gene delivery and portray the huge potential of these extremely versatile materials for such applications. Polyphosphazenes offer a number of distinct advantages as carriers for bioconjugates; alongside their completely degradable backbone, to non-toxic degradation products, they possess an inherently and uniquely high functionality and, thanks to recent advances in their polymer chemistry, can be prepared with controlled molecular weights and narrow polydispersities, as well as self-assembled supra-molecular structures. Importantly, the rate of degradation/hydrolysis of the polymers can be carefully tuned to suit the desired application. In this review we detail the recent developments in the chemistry of polyphosphazenes, relevant to drug and gene delivery and describe recent investigations into their application in this field. PMID:24729871

Teasdale, Ian; Brüggemann, Oliver

2014-01-01

384

Autonomous Rhythmic Drug Delivery Systems Based on Chemical and Biochemomechanical Oscillators  

Microsoft Academic Search

While many drug delivery systems target constant, or zero-order drug release, certain drugs and hormones must be delivered in rhythmic pulses in order to achieve their optimal effect. Here we describe studies with two model autonomous rhythmic delivery systems. The first system is driven by a pH oscillator that modulates the ionization state of a model drug, benzoic acid, which

Ronald A. Siegel

2009-01-01

385

J Drug Target . Author manuscript Targeted delivery of a proapoptotic peptide to tumors in vivo  

E-print Network

J Drug Target . Author manuscript Page /1 10 Targeted delivery of a proapoptotic peptide to tumors of perfectly controlled, targeted drug delivery systems. Author Keywords drug vectorization ; cancer ; integrin for tumour imaging and drug targeting. We designed the molecule RAFT-(c -RGDfK- ) , a constrained

Boyer, Edmond

386

Enzyme-responsive hydrogel microparticles for pulmonary drug delivery.  

PubMed

Poly(ethylene glycol) based hydrogel microparticles were developed for pulmonary drug delivery. Hydrogels are particularly attractive for pulmonary delivery because they can be size engineered for delivery into the bronchi, yet also swell upon reaching their destination to avoid uptake and clearance by alveolar macrophages. To develop enzyme-responsive hydrogel microparticles for pulmonary delivery a new synthesis method based on a solution polymerization was developed. This method produces spherical poly(ethylene glycol) (PEG) microparticles from high molecular weight poly(ethylene glycol) diacrylate (PEGDA)-based precursors that incorporate peptides in the polymer chain. Specifically, we have synthesized hydrogel microparticles that degrade in response to matrix metalloproteinases that are overexpressed in pulmonary diseases. Small hydrogel microparticles with sizes suitable for lung delivery by inhalation were obtained from solid precursors when PEGDA was dissolved in water at a high concentration. The average diameter of the particles was between 2.8 and 4 ?m, depending on the molecular weight of the precursor polymer used and its concentration in water. The relation between the physical properties of the particles and their enzymatic degradation is also reported, where an increased mesh size corresponds to increased degradation. PMID:24926532

Secret, Emilie; Kelly, Stefan J; Crannell, Kelsey E; Andrew, Jennifer S

2014-07-01

387

Carrier-free, functionalized pure drug nanorods as a novel cancer-targeted drug delivery platform  

NASA Astrophysics Data System (ADS)

A one-dimensional drug delivery system (1D DDS) is highly attractive since it has distinct advantages such as enhanced drug efficiency and better pharmacokinetics. However, drugs in 1D DDSs are all encapsulated in inert carriers, and problems such as low drug loading content and possible undesirable side effects caused by the carriers remain a serious challenge. In this paper, a novel, carrier-free, pure drug nanorod-based, tumor-targeted 1D DDS has been developed. Drugs are first prepared as nanorods and then surface functionalized to achieve excellent water dispersity and stability. The resulting drug nanorods show enhanced internalization rates mainly through energy-dependent endocytosis, with the shape-mediated nanorod (NR) diffusion process as a secondary pathway. The multiple endocytotic mechanisms lead to significantly improved drug efficiency of functionalized NRs with nearly ten times higher cytotoxicity than those of free molecules and unfunctionalized NRs. A targeted drug delivery system can be readily achieved through surface functionalization with targeting group linked amphipathic surfactant, which exhibits significantly enhanced drug efficacy and discriminates between cell lines with high selectivity. These results clearly show that this tumor-targeting DDS demonstrates high potential toward specific cancer cell lines.

Li, Yanan; Yang, Yinlong; An, Feifei; Liu, Zhuang; Zhang, Xiujuan; Zhang, Xiaohong

2013-01-01

388

Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine  

PubMed Central

Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. PMID:24039404

Hong, Xiaoyun; Wei, Liangming; Wu, Fei; Wu, Zaozhan; Chen, Lizhu; Liu, Zhenguo; Yuan, Weien

2013-01-01

389

Electrospun Nanofibers of Guar Galactomannan for Targeted Drug Delivery  

NASA Astrophysics Data System (ADS)

Guar galactomannan is a biodegradable polysaccharide used widely in the food industry but also in the cosmetics, pharmaceutical, oil drilling, textile and paper industries. Guar consists of a mannose backbone and galactose side groups that are both susceptible to enzyme degradation, a unique property that can be explored for targeted drug delivery especially since those enzymes are naturally secreted by the microflora in human colon. The present study can be divided into three parts. In the first part, we discuss ways to modify guar to produce nanofibers by electrospinning, a process that involves the application of an electric field to a polymer solution or melt to facilitate production of fibers in the sub-micron range. Nanofibers are currently being explored as the next generation of drug carriers due to its many advantages, none more important than the fact that nanofibers are on a size scale that is a fraction of a hair's width and have large surface-to-volume ratio. The incorporation and controlled release of nano-sized drugs is one way in which nanofibers are being utilized in drug delivery. In the second part of the study, we explore various methods to crosslink guar nanofibers as a means to promote water-resistance in a potential drug carrier. The scope and utility of water-resistant guar nanofibers can only be fully appreciated when subsequent drug release studies are carried out. To that end, the third part of our study focuses on understanding the kinetics and diffusion mechanisms of a model drug, Rhodamine B, through moderately-swelling (crosslinked) hydrogel nanofibers in comparison to rapidly-swelling (non-crosslinked) nanofibers. Along the way, our investigations led us to a novel electrospinning set-up that has a unique collector designed to capture aligned nanofibers. These aligned nanofiber bundles can then be twisted to hold them together like yarn. From a practical standpoint, these yarns are advantageous because they come freely suspended and without any attached support. As composites of aligned nanofibers, yarns potentially combine the inherent advantages of nanofibers with the strength and pliability of larger sized fibers. As such, we became interested in exploring the potential of nanofiber yarns as drug carriers. Our study evolved to accommodate comparative studies between the behavior of traditional nonwoven mats and nanofiber yarns. Throughout the process, we sought to answer the bigger question: Can guar galactomannan nanofibers be used as a new biodegradable platform for drug delivery?

Chu, Hsiao Mei Annie

2011-12-01

390

Project #15: Ravi Bellamkonda and Hongbin Han: Comparison of therapeutic efficacy of neuroprotective drugs between liposomal delivery and stereotactic simple diffusion delivery (SDD) via brain extracellular  

E-print Network

of neuroprotective drugs between liposomal delivery and stereotactic simple diffusion delivery (SDD) via brain extracellular space in the treatment of Alzheimer's disease Limited delivery of neuroprotective drugs into the central nervous system (CNS) by systemic administration has led to poor treatment efficacy. Drug delivery

Weber, Rodney

391

Nanostructured lipid carriers and their current application in targeted drug delivery.  

PubMed

In the last few decades, various drug-delivery technologies have emerged and a fascinating part of this has been the development of nanoscale drug delivery devices. Nanoparticles (NPs) and other colloidal drug-delivery systems modify the kinetics, drug distribution in the body and release profile of an associated drug. Nanostructured lipid carriers (NLCs) have been reported to be an alternative system to emulsions, liposomes, microparticles, solid lipid nanoparticles (SLNs) and their polymeric counterparts due to their numerous advantages. This paper basically reviews the types of NLCs, mechanism of skin penetration, stability related issues along with their production techniques, characterisation and applications towards targeted drug delivery. PMID:24813223

Jaiswal, Piyush; Gidwani, Bina; Vyas, Amber

2014-05-01

392

Lipid-based drug carriers for prodrugs to enhance drug delivery.  

PubMed

The combination of lipid drug delivery systems with prodrugs offers several advantages including improved pharmacokinetics, increased absorption, and facilitated targeting. Lipidization and use of lipid carriers can increase the pharmacological half-life of the drug, thus improving pharmacokinetics and allowing less frequent dosing. Lipids also offer advantages such as increased absorption through the intestines for oral drug absorption and to the CNS for brain delivery. Furthermore, the use of lipid delivery systems can enhance drug targeting. Endogenous proteins bind lipids in the blood and carry them to the liver to enable targeting of this organ. Drugs with significant side effects in the stomach can be specifically delivered to enterocytes by exploiting lipases for prodrug activation. Finally, lipids can be used to target the lymphatic system, thus bypassing the liver and avoiding first-pass metabolism. Lymphatic targeting is also important for antiviral drugs in the protection of B and T lymphocytes. In this review, both lipid-drug conjugates and lipid-based carriers will be discussed. An overview, including the chemistry and assembly of the systems, as well as examples from the clinic and in development, will be provided. PMID:25269430

Zaro, Jennica L

2015-01-01

393

Commercial potential for thermal & magnetic sensitive polymer in drug delivery applications  

E-print Network

Thermal and magnetically sensitive polymers are a new class of materials with unique properties suitable for applications in drug delivery. Specifically, these polymers can be combined with a drug reservoir to make a drug ...

Edward, Jonathan M. (Jonathan Mark)

2008-01-01

394

NIR-labeled perfluoropolyether nanoemulsions for drug delivery and imaging  

PubMed Central

Theranostic nanoparticle development recently took center stage in the field of drug delivery nanoreagent design. Theranostic nanoparticles combine therapeutic delivery systems (liposomes, micelles, nanoemulsions, etc.) with imaging reagents (MRI, optical, PET, CT). This combination allows for non-invasive in vivo monitoring of therapeutic nanoparticles in diseased organs and tissues. Here, we report a novel perfluoropolyether (PFPE) nanoemulsion with a water-insoluble lipophilic drug. The formulation enables non-invasive monitoring of nanoemulsion biodistribution using two imaging modalities, 19F MRI and near-infrared (NIR) optical imaging. The nanoemulsion is composed of PFPE-tyramide as a 19F MRI tracer, hydrocarbon oil, surfactants, and a NIR dye. Preparation utilizes a combination of self-assembly and high energy emulsification methods, resulting in droplets with average diameter 180 nm and low polydispersity index (PDI less than 0.2). A model nonsteroidal anti-inflammatory drug (NSAID), celecoxib, was incorporated into the formulation at 0.2 mg/mL. The reported nanoemulsion’s properties, including small particle size, visibility under 19F NMR and NIR fluorescence spectroscopy, and the ability to carry drugs make it an attractive potential theranostic agent for cancer imaging and treatment. PMID:22675234

O’Hanlon, Claire E.; Amede, Konjit G.; O’Hear, Meredith R.; Janjic, Jelena M.

2012-01-01

395

Drug carriers for the delivery of therapeutic peptides.  

PubMed

Peptides take on an increasingly important role as therapeutics in areas including diabetes, oncology, and metabolic, cardiovascular, and infectious diseases. In addition, many peptides such as insulin have been employed for many years. A challenge in the administration of peptide drugs is their often low hydrolytic stability, as well as other problems that are common to any drug treatment such as systemic distribution. There is a significant attention in the literature of protein drugs and their delivery strategies, but not many overviews are specifically dedicated to peptides. In this review, the different approaches to deliver peptides have been summarized where the focus is only on drug carriers based on organic materials. Initial discussion is on different methods of polymer-peptide conjugation before being followed by physical encapsulation techniques, which is divided into surfactant-based techniques and polymer carriers. Surfactant-based techniques are dominated by liposome, microemulsions and solid-lipid nanoparticles. The field widens further in the polymer field. The delivery of peptides has been enhanced using polymer-decorated liposomes, solid microspheres, polyelectrolyte complex, emulsions, hydrogels, and injectable polymers. The aim of this article is to give the reader an overview over the different types of carriers. PMID:24661025

Du, Alice W; Stenzel, Martina H

2014-04-14

396

Bionanocomposites containing magnetic graphite as potential systems for drug delivery.  

PubMed

New magnetic bio-hybrid matrices for potential application in drug delivery are developed from the assembly of the biopolymer alginate and magnetic graphite nanoparticles. Ibuprofen (IBU) intercalated in a Mg-Al layered double hydroxide (LDH) was chosen as a model drug delivery system (DDS) to be incorporated as third component of the magnetic bionanocomposite DDS. For comparative purposes DDS based on the incorporation of pure IBU in the magnetic bio-hybrid matrices were also studied. All the resulting magnetic bionanocomposites were processed as beads and films and characterized by different techniques with the aim to elucidate the role of the magnetic graphite on the systems, as well as that of the inorganic brucite-like layers in the drug-loaded LDH. In this way, the influence of both inorganic components on the mechanical properties, the water uptake ability, and the kinetics of the drug release from these magnetic systems were determined. In addition, the possibility of modulating the levels of IBU release by stimulating the bionanocomposites with an external magnetic field was also evaluated in in vitro assays. PMID:25455784

Ribeiro, Lígia N M; Alcântara, Ana C S; Darder, Margarita; Aranda, Pilar; Herrmann, Paulo S P; Araújo-Moreira, Fernando M; García-Hernández, Mar; Ruiz-Hitzky, Eduardo

2014-12-30

397

Drug Delivery by Tattooing to Treat Cutaneous Leishmaniasis  

PubMed Central

This study establishes a proof-of-concept that a tattoo device can target intra-dermal drug delivery against cutaneous leishmaniasis (CL). The selected drug is oleylphosphocholine (OlPC) formulated as liposomes, particles known to be prone to macrophage ingestion. We first show that treatment of cultured Leishmania-infected macrophages with OlPC-liposomes results in a direct dose-dependent killing of intracellular parasites. Based on this, in vivo efficacy is demonstrated using a 10 day tattooing-mediated treatment in mice infected with L. major and L. mexicana. In both models this regimen results in rapid clinical recovery with complete regression of skin lesions by Day 28. Parasite counts and histopathology examination confirm high treatment efficacy at the parasitic level. Low amount of drug required for tattooing combined with fast clinical recovery may have a positive impact on CL patient management. This first example of tattoo-mediated drug delivery could open to new therapeutic interventions in the treatment of skin diseases. PMID:24561704

Shio, Marina Temi; Paquet, Marilene; Martel, Caroline; Bosschaerts, Tom; Stienstra, Stef; Olivier, Martin; Fortin, Anny

2014-01-01

398

Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles.  

PubMed

The lymphatic system plays a crucial role in the immune system's recognition and response to disease, and most solid cancers initially spread from the primary site via the tumor's surrounding lymphatics before hematological dissemination. Hence, the lymphatic system is an important target for developing new vaccines, cancer treatments, and diagnostic agents. Targeting the lymphatic system by subcutaneous, intestinal, and pulmonary routes has been evaluated and subsequently utilized to improve lymphatic penetration and retention of drug molecules, reduce drug-related systemic toxicities, and enhance bioavailability of poorly soluble and unstable drugs. Lymphatic imaging is an essential tool for the detection and staging of cancer. New nano-based technologies offer improved detection and characterization of the nodal diseases, while new delivery devices can better target and confine treatments to tumors within the nodal space while sparing healthy tissues. This manuscript reviews recent advances in the field of lymphatic drug delivery and imaging and focuses specifically on the development of liposomes and solid lipid nanoparticles for lymphatic introduction via the subcutaneous, intestinal, and pulmonary routes. PMID:21712055

Cai, Shuang; Yang, Qiuhong; Bagby, Taryn R; Forrest, M Laird

2011-09-10

399

Biodegradable polymer-metal complexes for gene and drug delivery.  

PubMed

The delivery of genes and drugs into cells has increasingly attracted attention for the generation of genetically engineered cells. Successful drug delivery will have enormous academic, clinical, and practical impacts on gene therapy, cell and molecular biology, pharmaceutical and food industries, and bio-production. The major aim of gene therapy is to deliver genetic materials into cells effectively, genetically modifying and repairing cell functions with the possibility of inducing therapeutic healing of disease. The genetic material includes DNA, RNA, antisense, decoy DNA, and ribozymes. The aim is that the appropriate transfection would allow diseased cells to return to a healthy condition. The genetic manipulation is often manifested in the mechanisms of intracellular actions of genes and proteins, and may play an important role in making clear the key genes associated with various diseases. Based on fundamental and scientific knowledge, the delivery technology of genetic material should be applicable to producing various proteins of pharmaceutical value (e.g. cytokines, growth factors, and antibodies) and also to producing seeds resistant to harmful insects and cold weather damage. This implies that the cells might be enhanced to produce valuable pharmaceutical and food products. For each approach, it is important, for successful gene expression, to select an appropriate gene to be delivered as well as to develop the gene delivery technology to enhance transfection efficiency. This review will provide an overview of the enhanced gene expression of plasmid DNA complexed with new non-viral gene delivery vehicles by biodegradable biopolymer-metal complex, introducing our recent research data to emphasize the technical feasibility of biopolymer-metal complexes in gene therapy and biotechnology. PMID:19149528

Hosseinkhani, Hossein; Hosseinkhani, Mohsen

2009-01-01

400

Safe and efficient drug delivery system with liposomes for intrathecal application of an antivasospastic drug, fasudil.  

PubMed

Pharmacological treatment for cerebral ischemia and cerebral vasospasm following subarachnoid hemorrhage (SAH) cannot attain sufficiently high concentrations of the drugs in the cerebrospinal fluid (CSF) without precipitating systemic side effects. We recently developed a liposomal drug delivery system for intrathecal application that can maintain effective concentrations of cerebral vasodilator, fasudil, in the CSF. A single intrathecal injection of liposomal fasudil could maintain a therapeutic drug concentration in the CSF over a period time due to their sustained-release property, significantly decreasing infarct size in a rat model of acute ischemia and reducing vasoconstriction of the rat and dog basilar artery in a model of SAH. In this review, we are introducing our new less-invasive intrathecal drug delivery system that provides an alternative and safe method to deliver therapeutic agents. PMID:16508135

Ishida, Tatsuhiro; Takanashi, Yoshihiro; Kiwada, Hiroshi

2006-03-01

401

Nasal drug delivery - recent developments and future prospects.  

PubMed

The present review sets out to discuss recent developments and prospects of absorption promoters and absorption modulator systems being developed commercially by companies specialising in nasal drug delivery of normal small molecular weight drugs and biological drugs such as peptide and proteins. The absorption promoter systems selected for discussion in this review are those with the most promising preclinical and/or clinical data and sufficient toxicology data and/or company development efforts to warrant use in marketed products i.e. CPE-215 (cyclopenta decalactone (azone)) developed by CPEX Pharma, Intravail (alkylsaccharides) developed by Aegis Therapeutics, ChiSys(TM) (chitosan) and PecSys(TM) (low methylated pectin) in development by Archimedes Pharma and CriticalSorb(TM) (polyglycol mono- and diesters of 12-hydroxystearate (70%), polyethylene glycol (30%)) developed by Critical Pharmaceuticals. PMID:22300620

Illum, Lisbeth

2012-07-20

402

Topical Delivery of Aceclofenac: Challenges and Promises of Novel Drug Delivery Systems  

PubMed Central

Osteoarthritis (OA), a common musculoskeletal disorder, is projected to affect about 60 million people of total world population by 2020. The associated pain and disability impair the quality of life and also pose economic burden to the patient. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in OA, while diclofenac is the most prescribed one. Oral NSAIDs are not very patient friendly, as they cause various gastrointestinal adverse effects like bleeding, ulceration, and perforation. To enhance the tolerability of diclofenac and decrease the common side effects, aceclofenac (ACE) was developed by its chemical modification. As expected, ACE is more well-tolerated than diclofenac and possesses superior efficacy but is not completely devoid of the NSAID-tagged side effects. A series of chemical modifications of already planned drug is unjustified as it consumes quanta of time, efforts, and money, and this approach will also pose stringent regulatory challenges. Therefore, it is justified to deliver ACE employing tools of drug delivery and nanotechnology to refine its safety profile. The present review highlights the constraints related to the topical delivery of ACE and the various attempts made so far for the safe and effective topical delivery employing the novel materials and methods. PMID:25045671

Kumar, Manish; Kumar, Pramod; Malik, Ruchi; Sharma, Gajanand; Kaur, Manmeet; Katare, O. P.

2014-01-01

403

Topical delivery of aceclofenac: challenges and promises of novel drug delivery systems.  

PubMed

Osteoarthritis (OA), a common musculoskeletal disorder, is projected to affect about 60 million people of total world population by 2020. The associated pain and disability impair the quality of life and also pose economic burden to the patient. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in OA, while diclofenac is the most prescribed one. Oral NSAIDs are not very patient friendly, as they cause various gastrointestinal adverse effects like bleeding, ulceration, and perforation. To enhance the tolerability of diclofenac and decrease the common side effects, aceclofenac (ACE) was developed by its chemical modification. As expected, ACE is more well-tolerated than diclofenac and possesses superior efficacy but is not completely devoid of the NSAID-tagged side effects. A series of chemical modifications of already planned drug is unjustified as it consumes quanta of time, efforts, and money, and this approach will also pose stringent regulatory challenges. Therefore, it is justified to deliver ACE employing tools of drug delivery and nanotechnology to refine its safety profile. The present review highlights the constraints related to the topical delivery of ACE and the various attempts made so far for the safe and effective topical delivery employing the novel materials and methods. PMID:25045671

Raza, Kaisar; Kumar, Manish; Kumar, Pramod; Malik, Ruchi; Sharma, Gajanand; Kaur, Manmeet; Katare, O P

2014-01-01

404

Silk Fibroin as an Organic Polymer for Controlled Drug Delivery  

SciTech Connect

The pharmaceutical utility of silk fibroin (SF) materials for drug delivery was investigated. SF films were prepared from aqueous solutions of the fibroin protein polymer and crystallinity was induced and controlled by methanol treatment. Dextrans of different molecular weights, as well as proteins, were physically entrapped into the drug delivery device during processing into films. Drug release kinetics were evaluated as a function of dextran molecular weight, and film crystallinity. Treatment with methanol resulted in an increase in {beta}-sheet structure, an increase in crystallinity and an increase in film surface hydrophobicity determined by FTIR, X-ray and contact angle techniques, respectively. The increase in crystallinity resulted in the sustained release of dextrans of molecular weights ranging from 4 to 40 kDa, whereas for less crystalline films sustained release was confined to the 40 kDa dextran. Protein release from the films was studied with horseradish peroxidase (HRP) and lysozyme (Lys) as model compounds. Enzyme release from the less crystalline films resulted in a biphasic release pattern, characterized by an initial release within the first 36 h, followed by a lag phase and continuous release between days 3 and 11. No initial burst was observed for films with higher crystallinity and subsequent release patterns followed linear kinetics for HRP, or no substantial release for Lys. In conclusion, SF is an interesting polymer for drug delivery of polysaccharides and bioactive proteins due to the controllable level of crystallinity and the ability to process the biomaterial in biocompatible fashion under ambient conditions to avoid damage to labile compounds to be delivered.

Hofmann,S.; Wong Po Foo, C.; Rossetti, F.; Textor, M.; Vunjak-Novakovic, G.; Kaplan, D.; Merkle, H.; Meinel, L.

2006-01-01

405

MRI-Guided Focused Ultrasound as a New Method of Drug Delivery  

PubMed Central

Ultrasound-mediated drug delivery under the guidance of an imaging modality can improve drug disposition and achieve site-specific drug delivery. The term focal drug delivery has been introduced to describe the focal targeting of drugs in tissues with the help of imaging and focused ultrasound. Focal drug delivery aims to improve the therapeutic profile of drugs by improving their specificity and their permeation in defined areas. Focused-ultrasound- (FUS-) mediated drug delivery has been applied with various molecules to improve their local distribution in tissues. FUS is applied with the aid of microbubbles to enhance the permeability of bioactive molecules across BBB and improve drug distribution in the brain. Recently, FUS has been utilised in combination with MRI-labelled liposomes that respond to temperature increase. This strategy aims to “activate” nanoparticles to release their cargo locally when triggered by hyperthermia induced by FUS. MRI-guided FUS drug delivery provides the opportunity to improve drug bioavailability locally and therefore improve the therapeutic profiles of drugs. This drug delivery strategy can be directly translated to clinic as MRg FUS is a promising clinically therapeutic approach. However, more basic research is required to understand the physiological mechanism of FUS-enhanced drug delivery. PMID:23738076

Thanou, M.; Gedroyc, W.

2013-01-01

406

Potential of magnetic nanoparticles for targeted drug delivery  

PubMed Central

Nanoparticles (NPs) play an important role in the molecular diagnosis, treatment, and monitoring of therapeutic outcomes in various diseases. Their nanoscale size, large surface area, unique capabilities, and negligible side effects make NPs highly effective for biomedical applications such as cancer therapy, thrombolysis, and molecular imaging. In particular, nontoxic superparamagnetic magnetic NPs (MNPs) with functionalized surface coatings can conjugate chemotherapeutic drugs or be used to target ligands/proteins, making them useful for drug delivery, targeted therapy, magnetic resonance imaging, transfection, and cell/protein/DNA separation. To optimize the therapeutic efficacy of MNPs for a specific application, three issues must be addressed. First, the efficacy of magnetic targeting/guidance is dependent on particle magnetization, which can be controlled by adjusting the reaction conditions during synthesis. Second, the tendency of MNPs to aggregate limits their therapeutic use in vivo; surface modifications to produce high positive or negative charges can reduce this tendency. Finally, the surface of MNPs can be coated with drugs which can be rapidly released after injection, resulting in targeting of low doses of the drug. Drugs therefore need to be conjugated to MNPs such that their release is delayed and their thermal stability enhanced. This chapter describes the creation of nanocarriers with a high drug-loading capacity comprised of a high-magnetization MNP core and a shell of aqueous, stable, conducting polyaniline derivatives and their applications in cancer therapy. It further summarizes some newly developed methods to synthesize and modify the surfaces of MNPs and their biomedical applications. PMID:24198498

Yang, Hung-Wei; Hua, Mu-Yi; Liu, Hao-Li; Huang, Chiung-Yin; Wei, Kuo-Chen

2012-01-01

407

Chitosan in nasal delivery systems for therapeutic drugs.  

PubMed

There is an obvious need for efficient and safe nasal absorption enhancers for the development of therapeutically efficacious nasal products for small hydrophilic drugs, peptides, proteins, nucleic acids and polysaccharides, which do not easily cross mucosal membranes, including the nasal. Recent years have seen the development of a range of nasal absorption enhancer systems such as CriticalSorb (based on Solutol HS15) (Critical Pharmaceuticals Ltd), Chisys based on chitosan (Archimedes Pharma Ltd) and Intravail based on alkylsaccharides (Aegis Therapeutics Inc.), that is presently being tested in clinical trials for a range of drugs. So far, none of these absorption enhancers have been used in a marketed nasal product. The present review discusses the evaluation of chitosan and chitosan derivatives as nasal absorption enhancers, for a range of drugs and in a range of formulations such as solutions, gels and nanoparticles and finds that chitosan and its derivatives are able to efficiently improve the nasal bioavailability. The revirtew also questions whether chitosan nanoparticles for systemic drug delivery provide any real improvement over simpler chitosan formulations. Furthermore, the review also evaluates the use of chitosan formulations for the improvement of transport of drugs directly from the nasal cavity to the brain, based on its mucoadhesive characteristics and its ability to open tight junctions in the olfactory and respiratory epithelia. It is found that the use of chitosan nanoparticles greatly increases the transport of drugs from nose to brain over and above the effect of simpler chitosan formulations. PMID:24818769

Casettari, Luca; Illum, Lisbeth

2014-09-28

408

Potential of magnetic nanoparticles for targeted drug delivery.  

PubMed

Nanoparticles (NPs) play an important role in the molecular diagnosis, treatment, and monitoring of therapeutic outcomes in various diseases. Their nanoscale size, large surface area, unique capabilities, and negligible side effects make NPs highly effective for biomedical applications such as cancer therapy, thrombolysis, and molecular imaging. In particular, nontoxic superparamagnetic magnetic NPs (MNPs) with functionalized surface coatings can conjugate chemotherapeutic drugs or be used to target ligands/proteins, making them useful for drug delivery, targeted therapy, magnetic resonance imaging, transfection, and cell/protein/DNA separation. To optimize the therapeutic efficacy of MNPs for a specific application, three issues must be addressed. First, the efficacy of magnetic targeting/guidance is dependent on particle magnetization, which can be controlled by adjusting the reaction conditions during synthesis. Second, the tendency of MNPs to aggregate limits their therapeutic use in vivo; surface modifications to produce high positive or negative charges can reduce this tendency. Finally, the surface of MNPs can be coated with drugs which can be rapidly released after injection, resulting in targeting of low doses of the drug. Drugs therefore need to be conjugated to MNPs such that their release is delayed and their thermal stability enhanced. This chapter describes the creation of nanocarriers with a high drug-loading capacity comprised of a high-magnetization MNP core and a shell of aqueous, stable, conducting polyaniline derivatives and their applications in cancer therapy. It further summarizes some newly developed methods to synthesize and modify the surfaces of MNPs and their biomedical applications. PMID:24198498

Yang, Hung-Wei; Hua, Mu-Yi; Liu, Hao-Li; Huang, Chiung-Yin; Wei, Kuo-Chen

2012-01-01

409

Synthetic Aptamer-Polymer Hybrid Constructs for Programmed Drug Delivery into Specific Target Cells  

E-print Network

Synthetic Aptamer-Polymer Hybrid Constructs for Programmed Drug Delivery into Specific Target Cells effective drug delivery with fewer side effects.8,9 The systems that have made the greatest progress. They achieve this by performing a coordinated series of complex functions, resulting in delivery that is far

Akhmedov, Azer

410

Tunable physiologic interactions of adhesion molecules for inflamed cell-selective drug delivery  

E-print Network

Tunable physiologic interactions of adhesion molecules for inflamed cell-selective drug delivery delivery a b s t r a c t Dysregulated inflammation contributes to the pathogenesis of various diseases-directed drug delivery systems would thus render more effective and safer treatments by increasing local dosage

Daniel, Susan

411

A cell cycle automaton model for probing circadian patterns of anticancer drug delivery  

E-print Network

A cell cycle automaton model for probing circadian patterns of anticancer drug delivery Atilla 2006 Available online 28 June 2007 Abstract To optimize the temporal patterning of drug delivery used that the cytotoxic effect of 5-FU is minimum for the circadian delivery peaking at 4 a.m., and maximum

Goldbeter, Albert

412

Nanocapsules: The Weapons for Novel Drug Delivery Systems  

PubMed Central

Introduction Nanocapsules, existing in miniscule size, range from 10 nm to 1000 nm. They consist of a liquid/solid core in which the drug is placed into a cavity, which is surrounded by a distinctive polymer membrane made up of natural or synthetic polymers. They have attracted great interest, because of the protective coating, which are usually pyrophoric and easily oxidized and delay the release of active ingredients. Methods Various technical approaches are utilized for obtaining the nanocapsules; however, the methods of interfacial polymerization for monomer and the nano-deposition for preformed polymer are chiefly preferred. Most important characteristics in their preparation is particle size and size distribution which can be evaluated by using various techniques like X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolu¬tion transmission electron microscopy, X-ray photoelectron spectroscopy, superconducting quantum interference device, multi angle laser light scattering and other spectroscopic techniques. Results Nanocapsules possessing extremely high reproducibility have a broad range of life science applications. They may be applied in agrochemicals, genetic engineering, cosmetics, cleansing products, wastewater treatments, adhesive component applications, strategic delivery of the drug in tumors, nanocapsule bandages to fight infec¬tion, in radiotherapy and as liposomal nanocapsules in food science and agriculture. In addition, they can act as self-healing materials. Conclusion The enhanced delivery of bio¬active molecules through the targeted delivery by means of a nanocapsule opens numerous challenges and opportunities for the research and future development of novel improved therapies. PMID:23678444

Kothamasu, Pavankumar; Kanumur, Hemanth; Ravur, Niranjan; Maddu, Chiranjeevi; Parasuramrajam, Radhika; Thangavel, Sivakumar

2012-01-01

413

Nanostructured Surfaces for Drug Delivery and Anti-Fibrosis  

NASA Astrophysics Data System (ADS)

Effective and cost-efficient healthcare is at the forefront of public discussion; on both personal and policy levels, technologies that improve therapeutic efficacy without the use of painful hypodermic needle injections or the use of harsh chemicals would prove beneficial to patients. Nanostructured surfaces as structure-mediated permeability enhancers introduce a potentially revolutionary approach to the field of drug delivery. Parental administration routes have been the mainstay technologies for delivering biologics because these therapeutics are too large to permeate epithelial barriers. However, there is a significant patient dislike for hypodermic needles resulting in reduced patient compliance and poor therapeutic results. We present an alternative strategy to harness the body's naturally occurring biological processes and transport mechanisms to enhance the drug transport of biologics across the epithelium. Our strategy offers a paradigm shift from traditional biochemical drug delivery vehicles by using nanotopography to loosen the epithelial barrier. Herein, we demonstrate that nanotopographical cues can be used to enable biologics > 66 kDa to be transported across epithelial monolayers by increasing paracellular transport. When placed in contact with epithelial cells, nanostructured films significantly increase the transport of albumin, IgG, and a model therapeutic, etanercept. Our work highlights the potential to use drug delivery systems which incorporate nanotopographical cues to increase the transport of biologics across epithelial tissue. Furthermore, we describe current advancements in nano- and microfabrication for applications in anti-fibrosis and wound healing. Influencing cellular responses to biomaterials is crucial in the field of tissue engineering and regenerative medicine. Since cells are surrounded by extracellular matrix features that are on the nanoscale, identifying nanostructures for imparting desirable cellular function could greatly impact the field. Due to the rise in micro and nanofabrication techniques borrowed from the advances in the microelectronics industry, previously unattainable nanostructured surfaces on a variety of biomaterials can be generated. We investigated how nanostructured surfaces with varying nanofeature aspect ratios can influence fibrosis. Thus, nanostructured surfaces show substantial progress for therapeutic applications in drug delivery and wound healing.

Kam, Kimberly Renee

414

Chitosan-Derivative Based Hydrogels as Drug Delivery Platforms: Applications in Drug Delivery and Tissue Engineering  

Microsoft Academic Search

\\u000a Chitosan is a biodegradable, biocompatible and non-irritant polymer that exhibits good mechanical strength and adhesion. These\\u000a characteristics make it suitable for applications in controlled delivery systems and tissue engineering. Chitosan gels may\\u000a be easily obtained by a cross-linking reaction. These hydrogels exhibit good swelling properties and are widely used as a\\u000a temporary extracellular matrix in tissue engineering and regenerative medicine

Marta Roldo; Dimitrios G. Fatouros

415

Development of ocular drug delivery systems using molecularly imprinted soft contact lenses.  

PubMed

Abstract Recently, significant advances have been made in order to optimize drug delivery to ocular tissues. The main problems in ocular drug delivery are poor bioavailability and uncontrollable drug delivery of conventional ophthalmic preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new ocular drug delivery systems. Increase of hydrogel loading capacity, optimization of drug residence time on the ocular surface and biocompatibility with the eye tissue has been the main focus of previous studies. Molecular imprinting technology provided the opportunity to fulfill the above-mentioned objectives. Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel drug delivery systems for the treatment of eye disorders. This technique is used for the preparation of polymers with specific binding sites for a template molecule. Previous studies indicated that molecular imprinting technology could be successfully applied for the preparation of SCLs as ocular drug delivery systems. Previous research, particularly in vivo studies, demonstrated that molecular imprinting is a versatile and effective method in optimizing the drug release behavior and enhancing the loading capacity of SCLs as new ocular drug delivery systems. This review highlights various potentials of molecularly imprinted contact lenses in enhancing the drug-loading capacity and controlling the drug release, compared to other ocular drug delivery systems. We have also studied the effects of contributing factors such as the type of comonomer, template/functional monomer molar ratio, crosslinker concentration in drug-loading capacity, and the release properties of molecularly imprinted hydrogels. PMID:25113431

Tashakori-Sabzevar, Faezeh; Mohajeri, Seyed Ahmad

2014-08-12

416

Challenges in the delivery of peptide drugs: an industry perspective.  

PubMed

Due mainly to their poor stability and short plasma half-life, peptides are usually administered by injection, often several times daily. Injectable sustained-release formulations of peptides based on biodegradable polymer microparticles or implants early demonstrated the power of drug delivery technologies to enhance patient adherence and convenience, and increase safety and efficacy. Injectable sustained-release formulations are likely to remain a significant part of new peptide products. However, a new generation of technologies that enable solvent-free formulations and manufacturing processes, injection through narrow gauge needles and ready-to-use presentations will be increasingly used. In addition, the tremendous developments in noninvasive routes of delivery are likely to result in more and more peptides being delivered by the oral, transdermal, nasal or inhalation routes. PMID:25690084

Lewis, Andrew L; Richard, Joël

2015-02-01

417

Pharmaceutical and Toxicological Properties of Engineered Nanomaterials for Drug Delivery  

PubMed Central

Novel engineered nanomaterials (ENMs) are being developed to enhance therapy. The physicochemical properties of ENMs can be manipulated to control/direct biodistribution and target delivery, but these alterations also have implications for toxicity. It is well known that size plays a significant role in determining ENM effects since simply nanosizing a safe bulk material can render it toxic. However, charge, shape, rigidity, and surface modifications also have a significant influence on the biodistribution and toxicity of nanoscale drug delivery systems (NDDSs). In this review, NDDSs are considered in terms of platform technologies, materials, and physical properties that impart their pharmaceutical and toxicological effects. Moving forward, the development of safe and effective nanomedicines requires standardized protocols for determining the physical characteristics of ENMs as well as assessing their potential long-term toxicity. When such protocols are established, the remarkable promise of nanomedicine to improve the diagnosis and treatment of human disease can be fulfilled. PMID:24160695

Palombo, Matthew; Deshmukh, Manjeet; Myers, Daniel; Gao, Jieming; Szekely, Zoltan; Sinko, Patrick J.

2014-01-01

418

Silver nanoscale antisense drug delivery system for photoactivated gene silencing.  

PubMed

The unique photophysical properties of noble metal nanoparticles contribute to their potential as photoactivated drug delivery vectors. Here we demonstrate the synthesis and characterization of 60-80 nm silver nanoparticles (SNPs) decorated with thiol-terminated photolabile DNA oligonucleotides. In vitro assays and fluorescent confocal microscopy of treated cell cultures show efficient UV-wavelength photoactivation of surface-tethered caged ISIS2302 antisense oligonucleotides possessing internal photocleavable linkers. As a demonstration of the advantages of these novel nanocarriers, we investigate properties including: enhanced stability to nucleases, increased hybridization activity upon photorelease, and efficient cellular uptake as compared to commercial transfection vectors. Their potential as multicomponent delivery agents for oligonucleotide therapeutics is shown through regulation of ICAM-1 (Intracellular Adhesion Molecule-1) silencing. Our results suggest a means to achieve light-triggered, spatiotemporally controlled gene silencing via nontoxic silver nanocarriers, which hold promise as tailorable platforms for nanomedicine, gene expression studies, and genetic therapies. PMID:23473419

Brown, Paige K; Qureshi, Ammar T; Moll, Alyson N; Hayes, Daniel J; Monroe, W Todd

2013-04-23

419

Pharmaceutical and toxicological properties of engineered nanomaterials for drug delivery.  

PubMed

Novel engineered nanomaterials (ENMs) are being developed to enhance therapy. The physicochemical properties of ENMs can be manipulated to control/direct biodistribution and target delivery, but these alterations also have implications for toxicity. It is well known that size plays a significant role in determining ENM effects since simply nanosizing a safe bulk material can render it toxic. However, charge, shape, rigidity, and surface modifications also have a significant influence on the biodistribution and toxicity of nanoscale drug delivery systems (NDDSs). In this review, NDDSs are considered in terms of platform technologies, materials, and physical properties that impart their pharmaceutical and toxicological effects. Moving forward, the development of safe and effective nanomedicines requires standardized protocols for determining the physical characteristics of ENMs as well as assessing their potential long-term toxicity. When such protocols are established, the remarkable promise of nanomedicine to improve the diagnosis and treatment of human disease can be fulfilled. PMID:24160695

Palombo, Matthew; Deshmukh, Manjeet; Myers, Daniel; Gao, Jieming; Szekely, Zoltan; Sinko, Patrick J

2014-01-01

420

PEG-based degradable networks for drug delivery applications  

NASA Astrophysics Data System (ADS)

The controlled delivery of therapeutic agents by biodegradable hydrogels has become a popular mechanism for drug administration in recent years. Hydrogels are three-dimensional networks of polymer chains held together by crosslinks. Although the changes which the hydrogel undergoes in solution are important to a wide range of experimental studies, they have not been investigated systematically and the factors which influence the degree of swelling have not been adequately described. Hydrogels made of poly(ethylene glycol) (PEG) will generally resist degradation in aqueous conditions, while a hydrogel made from a copolymer of poly(lactic acid) (PLA) and PEG will degrade via hydrolysis of the lactic acid group. This ability to degrade makes these hydrogels promising candidates for controlled release drug delivery systems. The goal of this research was to characterize the swelling and degradation of both degradable and non-degradable gels and to evaluate the release of different drugs from these hydrogels, where the key variable is the molecular weight of the PEG segment. These hydrogels were formed by the addition and subsequent chemically crosslinking of methacrylate end groups. During crosslinking, both PEG and LA-PEG-LA hydrogels of varied PEG molecular weight were loaded with Vitamin B12, Insulin, Haloperidol, and Dextran. It was shown that increasing PEG molecular weight produces a hydrogel with larger pores, thus increasing water uptake and degradation rate. While many environmental factors do not affect the swelling behavior, they do significantly impact the degradation of the hydrogel, and thus the release of incorporated therapeutic agents.

Ostroha, Jamie L.

421

Gamma-sterilization-induced radicals in biodegradable drug delivery systems.  

PubMed

Electron paramagnetic resonance (EPR) spectroscopy (1.2 and 9.25 GHz, 25 degrees C) was used to characterize free radicals in gamma-ray sterilized biodegradable polymers of the type which are in clinical use. Free radicals were detected in all irradiated polymer samples. The temperature of irradiation (25 degrees C vs dry ice temperature) had only a minor influence on the yield of radicals and the shape of the EPR spectra. In contrast, the composition of the polymers and the drugs incorporated in them did strongly influence the amount of radiation-induced free radicals and their reactivity. In general, polymers with high melting points and crystallinity had the highest yields of radicals observable at room temperature. We were able to use the free radicals induced by the usual sterilization procedures to follow the penetration of water and the degradation of the polymers in vitro and in vivo. The ability of in vivo EPR to follow drug delivery noninvasively and continuously in vivo, using the free radicals induced in the usual sterilization process indicates that this approach could be applied immediately for the characterization of these drug delivery systems in experimental animals and in the near future should be able to be used in human subjects. PMID:9022208

Mäder, K; Domb, A; Swartz, H M

1996-01-01

422

Cubic and Hexagonal Liquid Crystals as Drug Delivery Systems  

PubMed Central

Lipids have been widely used as main constituents in various drug delivery systems, such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-based lyotropic liquid crystals. Among them, lipid-based lyotropic liquid crystals have highly ordered, thermodynamically stable internal nanostructure, thereby offering the potential as a sustained drug release matrix. The intricate nanostructures of the cubic phase and hexagonal phase have been shown to provide diffusion controlled release of active pharmaceutical ingredients with a wide range of molecular weights and polarities. In addition, the biodegradable and biocompatible nature of lipids demonstrates the minimum toxicity and thus they are used for various routes of administration. Therefore, the research on lipid-based lyotropic liquid crystalline phases has attracted a lot of attention in recent years. This review will provide an overview of the lipids used to prepare cubic phase and hexagonal phase at physiological temperature, as well as the influencing factors on the phase transition of liquid crystals. In particular, the most current research progresses on cubic and hexagonal phases as drug delivery systems will be discussed. PMID:24995330

Chen, Yulin; Ma, Ping; Gui, Shuangying

2014-01-01

423

Ionic liquids as ingredients in topical drug delivery systems.  

PubMed

Because of their properties, ionic liquids (ILs) (Ranke et al.) offer many advantages in topical drug delivery systems. For example, ionic liquids can be used to increase the solubility of sparingly soluble drugs and to enhance their topical and transdermal delivery. Furthermore, ILs can be used either to synthesize active pharmaceutical ingredients or as antimicrobial ingredients. In the present work, the conventional oil-in-water (O/W) and water-in-oil (W/O) emulsions containing the hydrophilic IL [HMIM] [Cl] and the hydrophobic IL [BMIM] [PF6] were prepared, and the influence of the ILs on emulsion properties was evaluated. It was found that ILs could be successfully incorporated into the emulsion structure, resulting in stable formulations. The antimicrobial activity of ILs in the formulations was estimated, and their application as preservatives was confirmed by performing preservative efficacy tests. Evaluation of the in vitro cytotoxicity of the emulsions containing hydrophilic or hydrophobic ILs showed the low cytotoxicity of the carriers. Finally, penetration enhancement of a fluorescent dye as a model drug in the presence of ionic liquids was shown. PMID:23123180

Dobler, Dorota; Schmidts, Thomas; Klingenhöfer, Ines; Runkel, Frank

2013-01-30

424

Characterization of new drug delivery nanosystems using atomic force microscopy  

NASA Astrophysics Data System (ADS)

Liposomes are the most attractive lipid vesicles for targeted drug delivery in nanomedicine, behaving also as cell models in biophotonics research. The characterization of the micro-mechanical properties of drug carriers is an important issue and many analytical techniques are employed, as, for example, optical tweezers and atomic force microscopy. In this work, polyol hyperbranched polymers (HBPs) have been employed along with liposomes for the preparation of new chimeric advanced drug delivery nanosystems (Chi-aDDnSs). Aliphatic polyester HBPs with three different pseudogenerations G2, G3 and G4 with 16, 32, and 64 peripheral hydroxyl groups, respectively, have been incorporated in liposomal formulation. The atomic force microscopy (AFM) technique was used for the comparative study of the morphology and the mechanical properties of Chi-aDDnSs and conventional DDnS. The effects of both the HBPs architecture and the polyesters pseudogeneration number in the stability and the stiffness of chi-aDDnSs were examined. From the force-distance curves of AFM spectroscopy, the Young's modulus was calculated.

Spyratou, Ellas; Mourelatou, Elena A.; Demetzos, C.; Makropoulou, Mersini; Serafetinides, A. A.

2015-01-01

425

Targeted Liposomal Drug Delivery to Monocytes and Macrophages  

PubMed Central

As the role of monocytes and macrophages in a range of diseases is better understood, strategies to target these cell types are of growing importance both scientifically and therapeutically. As particulate carriers, liposomes naturally target cells of the mononuclear phagocytic system (MPS), particularly macrophages. Loading drugs into liposomes can therefore offer an efficient means of drug targeting to MPS cells. Physicochemical properties including size, charge and lipid composition can have a very significant effect on the efficiency with which liposomes target MPS cells. MPS cells express a range of receptors including scavenger receptors, integrins, mannose receptors and Fc-receptors that can be targeted by the addition of ligands to liposome surfaces. These ligands include peptides, antibodies and lectins and have the advantages of increasing target specificity and avoiding the need for cationic lipids to trigger intracellular delivery. The goal for targeting monocytes/macrophages using liposomes includes not only drug deliver