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1

Tuberculosis chemotherapy: current drug delivery approaches  

PubMed Central

Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance. PMID:16984627

du Toit, Lisa Claire; Pillay, Viness; Danckwerts, Michael Paul

2006-01-01

2

Current perspectives on intrathecal drug delivery  

PubMed Central

Advances in intrathecal analgesia and intrathecal drug delivery systems have allowed for a range of medications to be used in the control of pain and spasticity. This technique allows for reduced medication doses that can decrease the side effects typically associated with oral or parenteral drug delivery. Recent expert panel consensus guidelines have provided care paths in the treatment of nociceptive, neuropathic, and mixed pain syndromes. While the data for pain relief, adverse effect reduction, and cost-effectiveness with cancer pain control are compelling, the evidence is less clear for noncancer pain, other than spasticity. Physicians should be aware of mechanical, pharmacological, surgical, and patient-specific complications, including possible granuloma formation. Newer intrathecal drug delivery systems may allow for better safety and quality of life outcomes.

Bottros, Michael M; Christo, Paul J

2014-01-01

3

Oral transmucosal drug delivery--current status and future prospects.  

PubMed

Oral transmucosal drug delivery (OTDD) dosage forms have been available since the 1980s. In contrast to the number of actives currently delivered locally to the oral cavity, the number delivered as buccal or sublingual formulations remains relatively low. This is surprising in view of the advantages associated with OTDD, compared with conventional oral drug delivery. This review examines a number of aspects related to OTDD including the anatomy of the oral cavity, models currently used to study OTDD, as well as commercially available formulations and emerging technologies. The limitations of current methodologies to study OTDD are considered as well as recent publications and new approaches which have advanced our understanding of this route of drug delivery. PMID:24879936

Sattar, Mohammed; Sayed, Ossama M; Lane, Majella E

2014-08-25

4

Current Status of Intraperitoneal Antineoplastic Drug Delivery  

Microsoft Academic Search

Following the initial introduction of cytotoxic pharmaceutical agents into the armamentarium of physicians caring for patients with malignant disease, attempts were made to treat cancers involving the abdominal cavity (e.g., advanced cancers of the ovary stomach and colon) by instilling the drugs directly into this body compartment [1]. While these early efforts revealed malignant ascites formation could be reduced by

Maurie Markman

5

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

6

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

7

Analysis on the current status of targeted drug delivery to tumors  

PubMed Central

Targeted drug delivery to tumor sites is one of the ultimate goals in drug delivery. Recent progress in nanoparticle engineering has certainly improved drug targeting, but the results are not as good as expected. This is largely due to the fact that nanoparticles, regardless of how advanced they are, find the target as a result of blood circulation, like the conventional drug delivery systems do. Currently, the nanoparticle-based drug delivery to the target tumor tissues is based on wrong assumptions that most of the nanoparticles, either PEGylated or not, reach the target by the enhanced permeation and retention (EPR) effect. Studies have shown that so-called targeting moieties, i.e., antibodies or ligands, on the nanoparticle surface do not really improve delivery to target tumors. Targeted drug delivery to tumor sites is associated with highly complex biological, mechanical, chemical and transport phenomena, of which characteristics vary spatiotemporally. Yet, most of the efforts have been focused on design and surface manipulation of the drug carrying nanoparticles with relatively little attention to other aspects. This article examines the current misunderstandings and the main difficulties in targeted drug delivery. PMID:22800574

Kwon, Il Keun; Lee, Sang Cheon; Han, Bumsoo; Park, Kinam

2013-01-01

8

Electrospun matrices for localized drug delivery: current technologies and selected biomedical applications.  

PubMed

Electrospinning allows for the preparation of unique matrices with nano- to micrometer sized fibers using diverse materials and numerous fabrication techniques. A variety of post-spinning modification techniques add to the large repertoire and enable development of tailored drug delivery systems. Herein we provide an overview on current developments regarding different techniques to manufacture electrospun matrices and achieve efficient drug loading and release. The delivery systems discussed employ a broad range of drugs from small molecules like antibiotics to protein drugs such as growth factors as well as nucleic acids for gene delivery or mRNA knockdown. We further highlight various biomedical applications, where the combined features of fibrous electrospun matrices and drug delivery function have resulted in first valuable results or seem to bear interesting prospects. In summary, electrospun scaffolds are highly versatile systems for the incorporation of various drugs and allow for significant variation with regard to scaffold material, spatial design, and surface modification. However, the multiplicity of options and parameters to vary during development of electrospun scaffold based drug delivery systems may also have contributed to the small number of the concepts that were successfully translated into therapeutic reality. PMID:22342778

Meinel, Anne J; Germershaus, Oliver; Luhmann, Tessa; Merkle, Hans P; Meinel, Lorenz

2012-05-01

9

Ocular drug delivery.  

PubMed

Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases. PMID:20437123

Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

2010-09-01

10

Positron emission tomography image-guided drug delivery: current status and future perspectives.  

PubMed

Positron emission tomography (PET) is an important modality in the field of molecular imaging, which is gradually impacting patient care by providing safe, fast, and reliable techniques that help to alter the course of patient care by revealing invasive, de facto procedures to be unnecessary or rendering them obsolete. Also, PET provides a key connection between the molecular mechanisms involved in the pathophysiology of disease and the according targeted therapies. Recently, PET imaging is also gaining ground in the field of drug delivery. Current drug delivery research is focused on developing novel drug delivery systems with emphasis on precise targeting, accurate dose delivery, and minimal toxicity in order to achieve maximum therapeutic efficacy. At the intersection between PET imaging and controlled drug delivery, interest has grown in combining both these paradigms into clinically effective formulations. PET image-guided drug delivery has great potential to revolutionize patient care by in vivo assessment of drug biodistribution and accumulation at the target site and real-time monitoring of the therapeutic outcome. The expected end point of this approach is to provide fundamental support for the optimization of innovative diagnostic and therapeutic strategies that could contribute to emerging concepts in the field of "personalized medicine". This review focuses on the recent developments in PET image-guided drug delivery and discusses intriguing opportunities for future development. The preclinical data reported to date are quite promising, and it is evident that such strategies in cancer management hold promise for clinically translatable advances that can positively impact the overall diagnostic and therapeutic processes and result in enhanced quality of life for cancer patients. PMID:24865108

Chakravarty, Rubel; Hong, Hao; Cai, Weibo

2014-11-01

11

The effects of electric current applied to skin: A review for transdermal drug delivery  

Microsoft Academic Search

Electrical enhancement of transdermal drug delivery is limited by undesired side-effects, such as tissue damage and pain. To aid in the development of electrical protocols which safely increase transport across skin, this review discusses the effects of electrical current on: skin electrical properties; sensation, pain, and muscle stimulation; and safety considerations. Quantitative relationships are presented whenever possible. First, the magnitudes

Mark R. Prausnitz

1996-01-01

12

Combining Microbubbles and Ultrasound for Drug Delivery to Brain Tumors: Current Progress and Overview  

PubMed Central

Malignant glioma is one of the most challenging central nervous system (CNS) diseases, which is typically associated with high rates of recurrence and mortality. Current surgical debulking combined with radiation or chemotherapy has failed to control tumor progression or improve glioma patient survival. Microbubbles (MBs) originally serve as contrast agents in diagnostic ultrasound but have recently attracted considerable attention for therapeutic application in enhancing blood-tissue permeability for drug delivery. MB-facilitated focused ultrasound (FUS) has already been confirmed to enhance CNS-blood permeability by temporally opening the blood-brain barrier (BBB), thus has potential to enhance delivery of various kinds of therapeutic agents into brain tumors. Here we review the current preclinical studies which demonstrate the reports by using FUS with MB-facilitated drug delivery technology in brain tumor treatment. In addition, we review newly developed multifunctional theranostic MBs for FUS-induced BBB opening for brain tumor therapy. PMID:24578726

Liu, Hao-Li; Fan, Ching-Hsiang; Ting, Chien-Yu; Yeh, Chih-Kuang

2014-01-01

13

Intracochlear Drug Delivery Systems  

PubMed Central

Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

Borenstein, Jeffrey T.

2011-01-01

14

Nanostructure-based platforms-current prospective in ophthalmic drug delivery  

PubMed Central

The topically applied drugs as drops are washed off from the eye in very short period, resulting in low ocular bioavailability of drugs. Number of approaches have been attempted to increase the bioavailability and the duration of action of ocular drugs. This review provides an insight into various novel approaches; hydrophilic nanogels, solid lipid nanoparticles, and nanosponges applied very recently in the delivery of insoluble drugs, prolonging the ocular residence time, minimize pre-corneal drug loss and, therefore, bioavailability and therapeutic efficacy of the drugs. Despite various scientific approaches, efficient ocular drug delivery remains a challenge for pharmaceutical scientists. PMID:25116766

Sharma, Rakesh Kumar; Yassin, Alaa Eldeen B

2014-01-01

15

In situ drug delivery.  

PubMed Central

Drug delivery to tumours and the accessibility of tumour cells to drugs remains a problem of foremost importance and is affected by many factors. We will discuss models we have developed for drug delivery from tumour capillaries to tumour cells, and drug delivery from well perfused, well oxygenated tumour regions to less well perfused hypoxic regions in terms of computer simulation of drug delivery for the anticancer agent BCNU and the hypoxic cell radiosensitizer misonidazole. PMID:6932949

Levin, V. A.; Wright, D. C.; Landahl, H. D.; Patlak, C. S.; Csejtey, J.

1980-01-01

16

Transdermal drug delivery  

Microsoft Academic Search

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, noncavitational ultrasound and iontophoresis have also resulted

Mark R Prausnitz; Robert Langer

2008-01-01

17

MRI in ocular drug delivery  

PubMed Central

Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. PMID:18186077

Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

2008-01-01

18

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

19

Iontophoretic transdermal delivery of glycyrrhizin: effects of pH, drug concentration, co-ions, current intensity, and chemical enhancers.  

PubMed

The aim of the present study was to evaluate the feasibility of transdermal delivery of glycyrrhizin, an agent used in the treatment of chronic hepatitis C, by cathodal iontophoresis using Ag/AgCl electrodes in vitro. The effects of donor pH (pH 4-7), concentration of drug (0.025-0.2% (w/v)), concentration of external chloride ions (Cl(-)) (0-133 mM), current strength (0-0.5 mA/cm(2)), and permeation enhancers (urea and Tween 80) on the skin permeability of glycyrrhizin were examined in in vitro skin permeation studies using porcine ear skin as the membrane. The cumulative amount of permeated glycyrrhizin and the steady-state skin permeation flux of glycyrrhizin across porcine skin increased in a pH-dependent manner. The skin permeability of glycyrrhizin was independent of the concentration of drug and competed only with a high external Cl(-) concentration. The skin permeation flux of glycyrrhizin increased with the current (R(2)=0.8955). The combination of iontophoresis and enhancers provided an additive or synergistic effect, and a skin permeation flux of about 60 µg/h/cm(2) was achieved. The plasma concentration of glycyrrhizin in humans, extrapolated from the in vitro steady-state permeation flux across porcine skin, was within the therapeutic level. These results suggest that cathodal iontophoresis can be used as a transdermal drug delivery system for glycyrrhizin using reasonable patch sizes and acceptable levels of current intensity. PMID:24292789

Yamamoto, Rie; Takasuga, Shinri; Kominami, Katsuya; Sutoh, Chiyo; Kinoshita, Mine; Kanamura, Kiyoshi; Takayama, Kozo

2013-01-01

20

Mucoadhesive drug delivery systems  

PubMed Central

Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal). PMID:21430958

Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.

2011-01-01

21

Microfabricated drug delivery devices  

Microsoft Academic Search

We review newest developments in the design and fabrication of drug delivery devices based on micropatterned structures. Electronic devices have now reached a stage of dimensions comparable to those of biological macromolecules. This raises exciting possibilities for combining microelectronics and biotechnology to develop new technologies with unprecedented power and versatility. While molecular electronics use the unique self-assembly, switching and dynamic

J. Zachary Hilt; Nicholas A. Peppas

2005-01-01

22

Physically facilitating drug-delivery systems  

PubMed Central

Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years. PMID:22485192

Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

2012-01-01

23

Photomechanical drug delivery  

NASA Astrophysics Data System (ADS)

Photomechanical waves (PW) are generated by Q-switched or mode-locked lasers. Ablation is a reliable method for generating PWs with consistent characteristics. Depending on the laser wavelength and target material, PWs with different parameters can be generated which allows the investigation of PWs with cells and tissue. PWs have been shown to permeabilize the stratum corneum (SC) in vivo and facilitate the transport of drugs into the skin. Once a drug has diffused into the dermis it can enter the vasculature, thus producing a systemic effect. Fluorescence microscopy of biopsies show that 40-kDa molecules can be delivered to a depth of > 300 micrometers into the viable skin of rats. Many important drugs such as insulin, and erythropoietin are smaller or comparable in size, making the PWs attractive for transdermal drug delivery. There are three possible pathways through the SC: Transappendageal via hair follicles or other appendages, transcellular through the corneocytes, and intercellular via the extracellular matrix. The intracellular route appears to be the most likely pathway of drug delivery through the SC.

Doukas, Apostolos G.; Lee, Shun

2000-05-01

24

Bioinspired drug delivery systems.  

PubMed

The way Nature designs, processes and assembles molecular building blocks to fabricate high performance materials with a minimum of resources is a suitable model for the design of drug delivery systems (DDS) with advanced functionalities. Bioinspired preparation methods that involve the use of superhydrophobic surfaces, layer-by-layer assembly or protein-driven growth are being successfully implemented to create a wide range of polymeric and hybrid structures. Mimicking the surface, shape, texture and movement of cells and microorganisms help to overcome phagocytosis and attain efficient targeting of the drug carriers, while transposition of the feed-back regulation mechanisms and the functions of membrane channels and physiological receptors may notably enhance the spatiotemporal control of drug release. These aspects are addressed in the present review. PMID:23465754

Alvarez-Lorenzo, Carmen; Concheiro, Angel

2013-12-01

25

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

26

Ultrasound and transdermal drug delivery  

Microsoft Academic Search

Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Application of ultrasound to the skin increases its permeability (sonophoresis) and enables the delivery of various substances into and through the skin. This review presents

Ilana Lavon; Joseph Kost

2004-01-01

27

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

28

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

29

Nanoparticles for Targeted Drug Delivery  

E-print Network

Nanoparticles were synthesized and modified for target drug delivery. The research involved the aqueous synthesis of near infrared (NIR) sensitive Au-Au2S nanoparticles. An anti-cancer drug (cis-platin) ...

Chow, Gan-Moog

30

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

31

Transdermal drug delivery: Microfabrication insights  

Microsoft Academic Search

The paper presented an enhancement solution for transdermal drug delivery using microneedles array with biodegradable tips. The microneedles array was fabricated by using deep reactive ion etching (DRIE) and the biodegradable tips were made to be porous by electrochemical etching process. The porous silicon microneedle tips can greatly enhance the transdermal drug delivery in a minimum invasion, painless, and convenient

Ciprian Iliescu; Bangtao Chen; Jiashen Wei; Zhilian Yue

2009-01-01

32

Osmotic micropumps for drug delivery.  

PubMed

This paper reviews miniaturized drug delivery systems applying osmotic principles for pumping. Osmotic micropumps require no electrical energy and consequently enable drug delivery systems of smallest size for a broad field of new applications. In contrast to common tablets, these pumps provide constant (zero-order) drug release rates. This facilitates systems for long term use not limited by gastrointestinal transit time and first-pass metabolism. The review focuses on parenteral routes of administration targeting drug delivery either in a site-specific or systemic way. Osmotic pumps consist of three building blocks: osmotic agent, solvent, and drug. This is used to categorize pumps into (i) single compartment systems using water from body fluids as solvent and the drug itself as the osmotic agent, (ii) two compartment systems employing a separate osmotic agent, and (iii) multi-compartment architectures employing solvent, drug and osmotic agent separately. In parallel to the micropumps, relevant applications and therapies are discussed. PMID:22370615

Herrlich, Simon; Spieth, Sven; Messner, Stephan; Zengerle, Roland

2012-11-01

33

Drug Delivery Systems for Platinum Drugs  

NASA Astrophysics Data System (ADS)

Since the discovery of cisplatin, drugs based on platinum, have made a significant impact on the treatment of various cancers. The administration of platinum drugs is however accompanied by significant side effects. This chapter discusses the types of drug delivery systems that have been developed in order to enable the targeted delivery while maintaining controlled temporal supply of the drug. The sizes of carriers range from nanometer to micrometer sized particles. The most common types of drug carriers are micelles, liposomes, nanoparticles, and dendrimers, but also a few microspheres have been developed. Most striking aspect of the delivery of platinum drugs is the possibility of physical encapsulation but also the binding of the drug to the polymer carrier coordinate covalent bond. Since platinum drugs have typically two permanent and two leaving ligands, the polymer can be part of either ligand. As the leaving ligand, the platinum drug is released often as cisplatin. If the polymer provides the functionality for the permanent ligand, a new macromolecular drug has been formed. In addition to the attachment of pt(II) drugs, recent offorts are devoted to the conjugation via the Pt((IV) prodrug.

Huynh, Vien T.; Scarano, Wei; Stenzel, Martina H.

2013-09-01

34

Chitosan microspheres in novel drug delivery systems.  

PubMed

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

2011-07-01

35

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

36

Colloidal drug delivery systems in vaccine delivery.  

PubMed

Vaccines play a vital role in the field of community medicine to combat against several diseases of human existence. Vaccines primarily trigger the acquired immune system to develop long-lasting immunity against pathogens. Conventional approaches for vaccine delivery lacks potential to target a particular antigen to develop acquired immunity by specific antibodies. Recent advancements in vaccine delivery showed that inclusion of adjuvants in vaccine formulations or delivery of them in a carrier helps in achieving desired targeting ability, reducing the immunogenicity and significant augmentation in the immune response. Colloidal carriers (liposomes, niosomes, microspheres, proteosomes, virosomes and virus like particles (VLPs), antigen cochleates, dendrimers and carbon nanotubes) have been widely explored for vaccine delivery. Further, surface engineering of these carriers with ligands, functional moieties and monoclonal antibodies tend to enhance the immune recognition potential of vaccines by differentiation of antigen specific memory T-cells. The current review, therefore, provides an updated account on the recent advancements in various colloidal delivery systems in vaccine delivery, outlining the mechanism of immune response initiated by them along with potential applications and marketed instances in an explicit manner. PMID:23072326

Beg, Sarwar; Samad, Abdus; Nazish, Iram; Sultana, Ruksar; Rahman, Mahfoozur; Ahmad, Md Zaki; Akbar, Md

2013-01-01

37

Supplementary Data Drug delivery  

E-print Network

to polymerize and dry at room temperature for 12 to 36 hours depending on the ambient humidity. 2. "Yeast paste temperature for 12 to 36 hours depending on the ambient humidity. 3. "On food" delivery: Appropriate volumes then allowed to dry at room temperature for 12 to 36 hours depending on the ambient humidity. Fly Cultures

Seroude, Laurent

38

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

39

Anticancer drug delivery with nanoparticles.  

PubMed

Nanotechnology provides a variety of nanoscale tools for medicine. Among them nanoparticles are revolutionizing the field of drug delivery. These drug nanocarriers have the potential to enhance the therapeutic efficacy of a drug, since they can be engineered to modulate the release and the stability and to prolong the circulation time of a drug, protecting it from elimination by phagocytic cells or premature degradation. Moreover, nanoscale carriers can be tailored to accumulate in tumour cells and tissues, due to enhanced permeability and a retention effect or by active targeting using ligands designed to recognize tumour-associated antigens. Could these nanomedicine tools mark an end to the necessity for loco-regional drug delivery? PMID:17203748

Conti, Matteo; Tazzari, Valeria; Baccini, Cesare; Pertici, Gianni; Serino, Lorenzo Pio; De Giorgi, Ugo

2006-01-01

40

Graphing Current Drug Data  

NSDL National Science Digital Library

Graphing Current Drug Data gives (1) some current views on the drug issue, (2) a history of drug use, (3) specific data on alcohol, caffeine, cocaine, marijuana and nicotine, and (4) data on high school drug trends from 1975-1985. The unit could supply graphing data for any math class 7-12, and could also be used in a social studies class.

2007-04-18

41

Nanocarriers for delivery of platinum anticancer drugs?  

PubMed Central

Platinum based anticancer drugs have revolutionized cancer chemotherapy, and continue to be in widespread clinical use especially for management of tumors of the ovary, testes, and the head and neck. However, several dose limiting toxicities associated with platinum drug use, partial anti-tumor response in most patients, development of drug resistance, tumor relapse, and many other challenges have severely limited the patient quality of life. These limitations have motivated an extensive research effort towards development of new strategies for improving platinum therapy. Nanocarrier-based delivery of platinum compounds is one such area of intense research effort beginning to provide encouraging preclinical and clinical results and may allow the development of the next generation of platinum chemotherapy. This review highlights current understanding on the pharmacology and limitations of platinum compounds in clinical use, and provides a comprehensive analysis of various platinum–polymer complexes, micelles, dendrimers, liposomes and other nanoparticles currently under investigation for delivery of platinum drugs. PMID:24113520

Oberoi, Hardeep S.; Nukolova, Natalia V.; Kabanov, Alexander V.; Bronich, Tatiana K.

2014-01-01

42

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

43

Nanotech approaches to drug delivery and imaging  

Microsoft Academic Search

Nanotechnology, a multidisciplinary scientific undertaking, involves creation and utilization of materials, devices or systems on the nanometer scale. The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to create innovations and play a critical role in various biomedical applications, not only in drug delivery, but also in molecular imaging, biomarkers and biosensors. Target-specific

Sanjeeb K. Sahoo; Vinod Labhasetwar

2003-01-01

44

Micromachined needles for the transdermal delivery of drugs  

Microsoft Academic Search

Although modern biotechnology has produced extremely sophisticated and potent drugs, many of these compounds cannot be effectively delivered using current drug delivery techniques (e.g., pills and injections). Administration across skin by transdermal drug delivery is an attractive alternative, but it is limited by the remarkably poor permeability of the skin. Because the primary barrier to transport is located in the

S. Henry; D. V. McAllister; M. G. Allen; M. R. Prausnitz

1998-01-01

45

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.

46

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

47

Gelatin Used for Drug Delivery  

NSDL National Science Digital Library

In this activity, learners discover how gelatin can be used as a medium for drug delivery. Learners create colored gelatin and then cut out pieces of the gelatin to simulate medicine (pills). Learners then put their simulated pills in a pan of hot water. Since gelatin is a thermoreversible or cold-setting polymer, gelatin will convert back to a liquid if put in a hot environment. As the gelatin returns to its liquid form, it releases its embedded dye. The dye eventually diffuses completely out of the gelatin which simulates the slow release of a drug from a pill. From this activity, learners learn more about diffusion and drug delivery. Adult supervision recommended.

Mississippi, University O.

2003-01-01

48

Nanoparticulate delivery systems for antiviral drugs.  

PubMed

Nanomedicine opens new therapeutic avenues for attacking viral diseases and for improving treatment success rates. Nanoparticulate-based systems might change the release kinetics of antivirals, increase their bioavailability, improve their efficacy, restrict adverse drug side effects and reduce treatment costs. Moreover, they could permit the delivery of antiviral drugs to specific target sites and viral reservoirs in the body. These features are particularly relevant in viral diseases where high drug doses are needed, drugs are expensive and the success of a therapy is associated with a patient's adherence to the administration protocol. This review presents the current status in the emerging area of nanoparticulate delivery systems in antiviral therapy, providing their definition and description, and highlighting some peculiar features. The paper closes with a discussion on the future challenges that must be addressed before the potential of nanotechnology can be translated into safe and effective antiviral formulations for clinical use. PMID:21107015

Lembo, David; Cavalli, Roberta

2010-01-01

49

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

50

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

51

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

52

Ultrasound mediated nanoparticle drug delivery  

NASA Astrophysics Data System (ADS)

Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems. Ultrasound parameters are optimized to achieve maximum cell internalization of molecules and increased nanoparticle delivery to a cell layer on a coverslip. In-vivo studies demonstrate the possibility of using a lower dose of paclitaxel to slow tumor growth rates, increase doxorubicin concentration in tumor tissue, and enhance tumor delivery of fluorescent molecules through treatments that combine nanoparticles with ultrasound and microbubbles.

Mullin, Lee B.

53

New Approaches to Targeted Drug Delivery  

NASA Astrophysics Data System (ADS)

For targeted drug delivery, one of the primary drawbacks lies with the inability to design a delivery system that can be loaded with a variety of drugs and biomolecules. Motivated by this challenge, we will present data showing 400 nm liposomes loaded via the novel method of lysenin pores. These pores are approximately 3 nm in diameter and can be closed with divalent and trivalent ions in addition to charged polymers. This new method allows for the controllable passage of large biomolecules such as DNA and protein without the inherent problems common to active and passive loading methods. We will show proof-of-concept results of this method using fluorescent calcein as a drug simulator. Furthermore, data demonstrating current attempts at loading DNA will also be presented.

Cooper, James; Oliver, William; Fologea, Daniel

2013-03-01

54

Nanoparticle drug delivery enhances the cytotoxicity of hydrophobichydrophilic drug conjugates  

E-print Network

Nanoparticle drug delivery enhances the cytotoxicity of hydrophobic­hydrophilic drug conjugates, Accepted 4th October 2011 DOI: 10.1039/c1jm13834k We report a drug conjugation approach to concurrently load both hydrophobic and hydrophilic drugs into the same drug delivery nanocarrier in a precisely

Zhang, Liangfang

55

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

56

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

57

Transdermal drug delivery: from micro to nano  

NASA Astrophysics Data System (ADS)

Delivery across skin offers many advantages compared to oral or intravenous routes of drug administration. Skin however is highly impermeable to most molecules on the basis of size, hydrophilicity, lipophilicity and charge. For this reason it is often necessary to temporarily alter the barrier properties of skin for effective administration. This can be done by applying chemical enhancers, which alter the lipid structure of the top layer of skin (the stratum corneum, SC), by applying external forces such as electric currents and ultrasounds, by bypassing the stratum corneum via minimally invasive microneedles or by using nano-delivery vehicles that can cross and deliver their payload to the deeper layers of skin. Here we present a critical summary of the latest technologies used to increase transdermal delivery.

Pegoraro, Carla; MacNeil, Sheila; Battaglia, Giuseppe

2012-03-01

58

Continuous drug delivery in Parkinson's disease.  

PubMed

Development of motor and non-motor complications during the course of Parkinson's disease (PD) is a major challenge for therapeutic management. At advanced disease stages, patients frequently fluctuate between PD symptoms-such as bradykinesia-and dyskinesias, in response to fluctuations in drug concentrations. Continuous subcutaneous infusion of the dopamine agonist apomorphine or intestinal infusion of levodopa reduce such fluctuations in both pharmacokinetics and motor function. This is the basis for the concept of continuous drug delivery in PD, and the more theoretical concept of continuous dopaminergic stimulation. These expressions are sometimes used to describe a treatment that is more continuous in its pharmacokinetic profile or that produces more sustained effects, compared with immediate-release levodopa, i.e. not only pump treatments. For example, sustained-release formulations of levodopa or dopamine agonists, transdermal delivery of rotigotine, and addition of catechol-O-methyltransferase inhibitors or monoamine oxidase-B inhibitors have been developed with the aim to provide more continuous drug concentrations, sustained benefits and minimized side effects. Progress has been made, but there are still knowledge gaps regarding how these treatment alternatives can be optimally used. New treatments are currently being developed to provide the continuous drug delivery that is known to successfully alleviate motor and non-motor complications. Hopefully, although not yet proven, these new methods may also prevent or postpone some of the late-stage complications. PMID:24323838

Senek, Marina; Nyholm, Dag

2014-01-01

59

Amphiphilic block copolymers for drug delivery.  

PubMed

Amphiphilic block copolymers (ABCs) have been used extensively in pharmaceutical applications ranging from sustained-release technologies to gene delivery. The utility of ABCs for delivery of therapeutic agents results from their unique chemical composition, which is characterized by a hydrophilic block that is chemically tethered to a hydrophobic block. In aqueous solution, polymeric micelles are formed via the association of ABCs into nanoscopic core/shell structures at or above the critical micelle concentration. Upon micellization, the hydrophobic core regions serve as reservoirs for hydrophobic drugs, which may be loaded by chemical, physical, or electrostatic means, depending on the specific functionalities of the core-forming block and the solubilizate. Although the Pluronics, composed of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide), are the most widely studied ABC system, copolymers containing poly(L-amino acid) and poly(ester) hydrophobic blocks have also shown great promise in delivery applications. Because each ABC has unique advantages with respect to drug delivery, it may be possible to choose appropriate block copolymers for specific purposes, such as prolonging circulation time, introduction of targeting moieties, and modification of the drug-release profile. ABCs have been used for numerous pharmaceutical applications including drug solubilization/stabilization, alteration of the pharmacokinetic profile of encapsulated substances, and suppression of multidrug resistance. The purpose of this minireview is to provide a concise, yet detailed, introduction to the use of ABCs and polymeric micelles as delivery agents as well as to highlight current and past work in this area. PMID:12820139

Adams, Monica L; Lavasanifar, Afsaneh; Kwon, Glen S

2003-07-01

60

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

61

Polymers for Colon Targeted Drug Delivery  

PubMed Central

The colon targeted drug delivery has a number of important implications in the field of pharmacotherapy. Oral colon targeted drug delivery systems have recently gained importance for delivering a variety of therapeutic agents for both local and systemic administration. Targeting of drugs to the colon via oral administration protect the drug from degradation or release in the stomach and small intestine. It also ensures abrupt or controlled release of the drug in the proximal colon. Various drug delivery systems have been designed that deliver the drug quantitatively to the colon and then trigger the release of drug. This review will cover different types of polymers which can be used in formulation of colon targeted drug delivery systems. PMID:21969739

Rajpurohit, H.; Sharma, P.; Sharma, S.; Bhandari, A.

2010-01-01

62

Biodegradable polymer microneedles: Fabrication, mechanics and transdermal drug delivery  

E-print Network

Biodegradable polymer microneedles: Fabrication, mechanics and transdermal drug delivery Jung the skin's barrier properties that block transdermal delivery of most drugs, arrays of microscopic needles; Transdermal drug delivery; Biodegradable polymer; Failure force 1. Introduction Most drugs are administered

63

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

64

Noninvasive ocular drug delivery: potential transcorneal and other alternative delivery routes for therapeutic molecules in glaucoma.  

PubMed

Drug delivery to the eye is made difficult by multiple barriers (such as the tear film, cornea, and vitreous) between the surface of the eye and the treatment site. These barriers are difficult to surmount for the purposes of drug delivery without causing toxicity. Using nanotechnology tools to control, manipulate, and study delivery systems, new approaches to delivering drugs, genes, and antigens that are effective and safe can be developed. Topical administration to the ocular surface would be the safest method for delivery, as it is noninvasive and painless compared with other delivery methods. However, there is only limited success using topical delivery methods, especially for gene therapy. Current thinking on treatments of the future enabled by nanodelivery systems and the identification of target specificity parameters that require deeper understanding to develop successful topical delivery systems for glaucoma is highlighted. PMID:25275915

Foldvari, Marianna

2014-01-01

65

Targeted drug delivery for brain cancer treatment  

Microsoft Academic Search

The blood brain barrier (BBB) and the systemic toxicity of conventional chemotherapy present obstacles to the success of future blood-borne drug therapies of brain tumors. The work with polymer-encapsulated cancer drugs suggests an alternative and more focused treatment approach. Our experimental strategy integrates direct intracerebral drug delivery, sustained drug release from liposomes or polymer implants, and increased targeting of the

Robert L Gutman; Gina Peacock; D. Robert Lu

2000-01-01

66

Pulmonary drug delivery systems: recent developments and prospects.  

PubMed

Targeting drug delivery into the lungs has become one of the most important aspects of systemic or local drug delivery systems. Consequently, in the last few years, techniques and new drug delivery devices intended to deliver drugs into the lungs have been widely developed. Currently, the main drug targeting regimens include direct application of a drug into the lungs, mostly by inhalation therapy using either pressurized metered dose inhalers (pMDI) or dry powder inhalers (DPI). Intratracheal administration is commonly used as a first approach in lung drug delivery in vivo. To convey a sufficient dose of drug to the lungs, suitable drug carriers are required. These can be either solid, liquid, or gaseous excipients. Liposomes, nano- and microparticles, cyclodextrins, microemulsions, micelles, suspensions, or solutions are all examples of this type of pharmaceutical carrier that have been successfully used to target drugs into the lungs. The use of microreservoir-type systems offers clear advantages, such as high loading capacity and the possibility of controlling size and permeability, and thus of controlling the release kinetics of the drugs from the carrier systems. These systems make it possible to use relatively small numbers of vector molecules to deliver substantial amounts of a drug to the target. This review discusses the drug carriers administered or intended to be administered into the lungs. The transition to CFC-free inhalers and drug delivery systems formulated with new propellants are also discussed. Finally, in addition to the various advances made in the field of pulmonary-route administration, we describe new systems based on perfluorooctyl bromide, which guarantee oxygen delivery in the event of respiratory distress and drug delivery into the lungs. PMID:12661699

Courrier, H M; Butz, N; Vandamme, Th F

2002-01-01

67

Transdermal delivery of drugs for the treatment of bone diseases  

Microsoft Academic Search

The current status of transdermal drug delivery for the treatment of bone diseases is described in this review. The structure, physiology and function of skin and their importance in determining delivery into and across skin are discussed. Special emphasis has been devoted to a description of the major pathways of transport across the skin and the quite continuing controversy over

Chandrasekharan Ramachandran; David Fleisher

2000-01-01

68

Impact of nanotechnology on drug delivery.  

PubMed

Nanotechnology is the engineering and manufacturing of materials at the atomic and molecular scale. In its strictest definition from the National Nanotechnology Initiative, nanotechnology refers to structures roughly in the 1-100 nm size regime in at least one dimension. Despite this size restriction, nanotechnology commonly refers to structures that are up to several hundred nanometers in size and that are developed by top-down or bottom-up engineering of individual components. Herein, we focus on the application of nanotechnology to drug delivery and highlight several areas of opportunity where current and emerging nanotechnologies could enable entirely novel classes of therapeutics. PMID:19206243

Farokhzad, Omid C; Langer, Robert

2009-01-27

69

Colloidal microgels in drug delivery applications  

PubMed Central

Colloidal microgels have recently received attention as environmentally responsive systems and now are increasingly used in applications as carriers for therapeutic drugs and diagnostic agents. Synthetic microgels consist of a crosslinked polymer network that provides a depot for loaded drugs, protection against environmental hazards and template for post-synthetic modification or vectorization of the drug carriers. The aim of this manuscript is to review recent attempts to develop new microgel formulations for oral drug delivery, to design metal-containing microgels for diagnostic and therapeutic applications, and to advance approaches including the systemic administration of microgels. Novel nanogel drug delivery systems developed in the authors’ laboratory are discussed in details including aspects of their synthesis, vectorization and recent applications for encapsulation of low molecular weight drugs or formulation of biological macromolecules. The findings reviewed here are encouraging for further development of the nanogels as intelligent drug carriers with such features as targeted delivery and triggered drug release. PMID:17168773

Vinogradov, Serguei V.

2005-01-01

70

76 FR 51038 - Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...  

Federal Register 2010, 2011, 2012, 2013

...Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...industry entitled ``Residual Drug in Transdermal and Related Drug Delivery Systems...developers and manufacturers of transdermal drug delivery systems...

2011-08-17

71

Survey of the current use of pharmacokinetic model-driven drug delivery in small animal anaesthesia and analgesia in Italy  

Microsoft Academic Search

Veterinary surgeons in Italy were surveyed about their current practice with regard to the use of propofol and intravenous opioids during anaesthesia and for treatment of acute pain in small animals. Questionnaires were e-mailed to all 171 members of the Italian Society of Veterinary Regional Anaesthesia and Pain Medicine. Information was requested on the type of practice the veterinarians worked

L. Novello; B. Carobbi

2010-01-01

72

Novel Approaches for Retinal Drug and Gene Delivery  

PubMed Central

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.

Kim, Stephen J.

2014-01-01

73

Nanotechnology-based drug delivery systems  

PubMed Central

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

74

Ocular Drug Delivery for Glaucoma Management  

PubMed Central

Current glaucoma management modalities are hindered by low patient compliance and adherence. This can be due to highly complex treatment strategies or poor patient understanding. Treatments focus on the management or reduction of intraocular pressure. This is most commonly done through the use of daily topical eye drops. Unfortunately, despite effective therapies, glaucoma continues to progress, possibly due to patients not adhering to their treatments. In order to mitigate these patient compliance issues, many sustained release treatments are being researched and are entering the clinic. Conjunctival, subconjunctival, and intravitreal inserts, punctal plugs, and drug depots are currently in clinical development. Each delivery system has hurdles, yet shows promise and could potentially mitigate the current problems associated with poor patient compliance. PMID:24300188

Gooch, Nathan; Molokhia, Sarah A.; Condie, Russell; Burr, Randon Michael; Archer, Bonnie; Ambati, Balamurali K.; Wirostko, Barbara

2012-01-01

75

Radiation sterilization of new drug delivery systems  

PubMed Central

Radiation sterilization has now become a commonly used method for sterilization of several active ingredients in drugs or drug delivery systems containing these substances. In this context, many applications have been performed on the human products that are required to be sterile, as well as on pharmaceutical products prepared to be developed. The new drug delivery systems designed to deliver the medication to the target tissue or organ, such as microspheres, nanospheres, microemulsion, and liposomal systems, have been sterilized by gamma (?) and beta (?) rays, and more recently, by e-beam sterilization. In this review, the sterilization of new drug delivery systems was discussed other than conventional drug delivery systems by ? irradiation. PMID:24936306

Abuhano?lu, Gürhan

2014-01-01

76

Recent expansions in an emergent novel drug delivery technology: Emulgel.  

PubMed

Emulgel is an emerging topical drug delivery system to which if more effort is paid towards its formulation & development with more number of topically effective drugs it will prove a boon for derma care & cosmetology. Emulgels are either emulsion of oil in water or water in oil type, which is gelled by mixing it with gelling agent. Incorporation of emulsion into gel increases its stability & makes it a dual control release system. Due to lack of excess oily bases & insoluble excipients, it shows better drug release as compared to other topical drug delivery system. Presence of gel phase makes it a non greasy & favors good patient compliance. These reviews give knowledge about Emulgel including its properties, advantages, formulation considerations, and its recent advances in research field. All factors such as selection of gelling agent, oil agent, emulsifiers influencing the stability and efficacy of Emulgel are discussed. All justifications are described in accordance with the research work carried out by various scientists. These brief reviews on formulation method have been included. Current research works that carried out on Emulgel are also discussed and highlighted the wide utility of Emulgel in topical drug delivery system. After the vast study, it can be concluded that the Emulgels appear better & effective drug delivery system as compared to other topical drug delivery system. The comprehensive analysis of rheological and release properties will provide an insight into the potential usage of Emulgel formulation as drug delivery system. PMID:23831051

Ajazuddin; Alexander, Amit; Khichariya, Ajita; Gupta, Saurabh; Patel, Ravish J; Giri, Tapan Kumar; Tripathi, Dulal Krishna

2013-10-28

77

Transdermal microneedles for drug delivery applications  

Microsoft Academic Search

Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to

Ai Ling Teo; Christopher Shearwood; Kian Chye Ng; Jia Lu; Shabbir Moochhala

2006-01-01

78

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

79

A Review of Current Intravaginal Drug Delivery Approaches Employed for the Prophylaxis of HIV\\/AIDS and Prevention of Sexually Transmitted Infections  

Microsoft Academic Search

The objective of this review is to describe the current status of several intravaginal anti-HIV microbicidal delivery systems\\u000a these delivery systems and microbicidal compounds in the context of their stage within clinical trials and their potential\\u000a cervicovaginal defence successes. The global Human Immuno-Deficiency Virus (HIV) pandemic continues to spread at a rate of\\u000a more than 15,000 new infections daily and

Valence M. K. Ndesendo; Viness Pillay; Yahya E. Choonara; Eckhart Buchmann; David N. Bayever; Leith C. R. Meyer

2008-01-01

80

Perspectives on transdermal ultrasound mediated drug delivery  

PubMed Central

The use of needles for multiple injection of drugs, such as insulin for diabetes, can be painful. As a result, prescribed drug noncompliance can result in severe medical complications. Several noninvasive methods exist for transdermal drug delivery. These include chemical mediation using liposomes and chemical enhancers or physical mechanisms such as microneedles, iontophoresis, electroporation, and ultrasound. Ultrasound enhanced transdermal drug delivery offers advantages over traditional drug delivery methods which are often invasive and painful. A broad review of the transdermal ultrasound drug delivery literature has shown that this technology offers promising potential for noninvasive drug administration. From a clinical perspective, few drugs, proteins or peptides have been successfully administered transdermally because of the low skin permeability to these relatively large molecules, although much work is underway to resolve this problem. The proposed mechanism of ultrasound has been suggested to be the result of cavitation, which is discussed along with the bioeffects from therapeutic ultrasound. For low frequencies, potential transducers which can be used for drug delivery are discussed, along with cautions regarding ultrasound safety versus efficacy. PMID:18203426

Smith, Nadine Barrie

2007-01-01

81

Diatoms: a biotemplating approach to fabricating drug delivery reservoirs.  

PubMed

Biotemplating is a rapidly expanding subfield that utilizes nature-inspired systems and structures to create novel functional materials, and it is through these methods that the limitations of current engineering practices may be advanced. The diatom is an exceptional template for drug delivery applications, owing largely to its highly-ordered pores, large surface area, species-specific architecture, and flexibility for surface modifications. Diatoms have been studied in a wide range of biomedical applications and their potential as the next frontier of drug delivery has yet to be fully exploited. In this editorial, the authors aim to review the use of diatoms in the delivery of poorly water-soluble drugs as reported in the literature, discuss the progress and advancements that have been made thus far, identify the shortcomings and limitations in the field, and, lastly, present their expert opinion and convey the future outlook on biotemplating approaches for drug delivery. PMID:25146231

Chao, Joshua T; Biggs, Manus Jp; Pandit, Abhay S

2014-11-01

82

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

83

Inner Ear Drug Delivery for Auditory Applications  

PubMed Central

Many inner ear disorders cannot be adequately treated by systemic drug delivery. A blood-cochlear barrier exists, similar physiologically to the blood-brain barrier, which limits the concentration and size of molecules able to leave the circulation and gain access to the cells of the inner ear. However, research in novel therapeutics and delivery systems has led to significant progress in the development of local methods of drug delivery to the inner ear. Intratympanic approaches, which deliver therapeutics to the middle ear, rely on permeation through tissue for access to the structures of the inner ear, whereas intracochlear methods are able to directly insert drugs into the inner ear. Innovative drug delivery systems to treat various inner ear ailments such as ototoxicity, sudden sensorineural hearing loss, autoimmune inner ear disease, and for preserving neurons and regenerating sensory cells are being explored. PMID:18848590

Swan, Erin E. Leary; Mescher, Mark J.; Sewell, William F.; Tao, Sarah L.; Borenstein, Jeffrey T.

2008-01-01

84

Synthetic micro/nanomotors in drug delivery  

NASA Astrophysics Data System (ADS)

Nanomachines offer considerable promise for the treatment of diseases. The ability of man-made nanomotors to rapidly deliver therapeutic payloads to their target destination represents a novel nanomedicine approach. Synthetic nanomotors, based on a multitude of propulsion mechanisms, have been developed over the past decade toward diverse biomedical applications. In this review article, we journey from the use of chemically powered drug-delivery nanovehicles to externally actuated (fuel-free) drug-delivery nanomachine platforms, and conclude with future prospects and challenges for such practical propelling drug-delivery systems. As future micro/nanomachines become more powerful and functional, these tiny devices are expected to perform more demanding biomedical tasks and benefit different drug delivery applications.

Gao, Wei; Wang, Joseph

2014-08-01

85

The Conjunctival Barrier in Ocular Drug Delivery  

Microsoft Academic Search

Within the context of topical and local drug delivery to the eye, the mammalian conjunctiva functions as a unique biological\\u000a barrier. Various model systems as in vitro tools have been refined and validated over the years to assess drug absorption\\u000a across the conjunctiva. Passive and active drug transport as well as endocytic routes of transconjunctival drug permeation\\u000a have been extensively

Hovhannes J. Gukasyan; Kwang-Jin Kim; Vincent H. L. Lee

86

Electrospun Nanofibers in Oral Drug Delivery  

Microsoft Academic Search

In order to enhance the delivery of drugs with limited absorption due to poor solubility\\/dissolution, approaches are being\\u000a developed to improve the dissolution rates and solubility of drug molecules. These approaches include identification of water-soluble\\u000a salts of parent drugs, preparation of stable amorphous drug formulations, inclusion of solubility-enhancing agents in the\\u000a dosage form, and particle size reduction. Technologies to reduce

Francis Ignatious; Linghong Sun; Chao-Pin Lee; John Baldoni

2010-01-01

87

Novel Platforms for Oral Drug Delivery  

Microsoft Academic Search

The aim of this review is to provide the reader general and inspiring prospects on recent and promising fields of innovation\\u000a in oral drug delivery. Nowadays, inventive drug delivery systems vary from geometrically modified and modular matrices, more\\u000a close to “classic” pharmaceutical manufacturing processes, to futuristic bio micro-electro-mechanical systems (bioMEMS), based\\u000a on manufacturing techniques borrowed from electronics and other fields.

P. Colombo; F. Sonvico; G. Colombo; R. Bettini

2009-01-01

88

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

89

Gastroretentive drug delivery systems for the treatment of Helicobacter pylori  

PubMed Central

Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world’s population. It is the primary known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. However, combined drug therapy as the general treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse reactions and poor patient compliance are major obstacles to the eradication of H. pylori. Oral site-specific drug delivery systems that could increase the longevity of the treatment agent at the target site might improve the therapeutic effect and avoid side effects. Gastroretentive drug delivery systems potentially prolong the gastric retention time and controlled/sustained release of a drug, thereby increasing the concentration of the drug at the application site, potentially improving its bioavailability and reducing the necessary dosage. Recommended gastroretentive drug delivery systems for enhancing local drug delivery include floating systems, bioadhesive systems and expandable systems. In this review, we summarize the important physiological parameters of the gastrointestinal tract that affect the gastric residence time. We then focus on various aspects useful in the development of gastroretentive drug delivery systems, including current trends and the progress of novel forms, especially with respect to their application for the treatment of H. pylori infections. PMID:25071326

Zhao, Shan; Lv, Yan; Zhang, Jian-Bin; Wang, Bing; Lv, Guo-Jun; Ma, Xiao-Jun

2014-01-01

90

Microneedles for drug and vaccine delivery  

PubMed Central

Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990’s when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. PMID:22575858

Kim, Yeu-Chun; Park, Jung-Hwan; Prausnitz, Mark R.

2012-01-01

91

Stimuli sensitive hydrogels for ophthalmic drug delivery: A review.  

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 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

2012-04-01

92

Recent Applications of Liposomes in Ophthalmic Drug Delivery  

PubMed Central

Liposomal formulations were significantly explored over the last decade for the ophthalmic drug delivery applications. These formulations are mainly composed of phosphatidylcholine (PC) and other constituents such as cholesterol and lipid-conjugated hydrophilic polymers. Liposomes are biodegradable and biocompatible in nature. Current approaches for topical delivery of liposomes are focused on improving the corneal adhesion and permeation by incorporating various bioadhesive and penetration enhancing polymers. In the case of posterior segment disorders improvement in intravitreal half life and targeted drug delivery to the retina is achieved by liposomes. In this paper we have attempted to summarize the applications of liposomes in the field of ophthalmic drug delivery by citing numerous investigators over the last decade. PMID:21490757

Mishra, Gyan P.; Bagui, Mahuya; Tamboli, Viral; Mitra, Ashim K.

2011-01-01

93

Microfabrication Technologies for Oral Drug Delivery  

PubMed Central

Micro-/nanoscale technologies such as lithographic techniques and microfluidics offer promising avenues to revolutionalize the fields of tissue engineering, drug discovery, diagnostics and personalized medicine. Microfabrication techniques are being explored for drug delivery applications due to their ability to combine several features such as precise shape and size into a single drug delivery vehicle. They also offer to create unique asymmetrical features incorporated into single or multiple reservoir systems maximizing contact area with the intestinal lining. Combined with intelligent materials, such microfabricated platforms can be designed to be bioadhesive and stimuli-responsive. Apart from drug delivery devices, microfabrication technologies offer exciting opportunities to create biomimetic gastrointestinal tract models incorporating physiological cell types, flow patterns and brush-border like structures. Here we review the recent developments in this field with a focus on the applications of microfabrication in the development of oral drug delivery devices and biomimetic gastrointestinal tract models that can be used to evaluate the drug delivery efficacy. PMID:22166590

Sant, Shilpa; Tao, Sarah L.; Fisher, Omar; Xu, Qiaobing; Peppas, Nicholas A.; Khademhosseini, Ali

2012-01-01

94

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

95

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

96

Ultrasonic Drug Delivery - A General Review  

PubMed Central

Ultrasound (US) has an ever-increasing role in the delivery of therapeutic agents including genetic material, proteins, and chemotherapeutic agents. Cavitating gas bodies such as microbubbles are the mediators through which the energy of relatively non-interactive pressure waves is concentrated to produce forces that permeabilize cell membranes and disrupt the vesicles that carry drugs. Thus the presence of microbubbles enormously enhances delivery of genetic material, proteins and smaller chemical agents. Delivery of genetic material is greatly enhanced by ultrasound in the presence of microbubbles. Attaching the DNA directly to the microbubbles or to gas-containing liposomes enhances gene uptake even further. US-enhanced gene delivery has been studied in various tissues including cardiac, vascular, skeletal muscle, tumor and even fetal tissue. US-enhanced delivery of proteins has found most application in transdermal delivery of insulin. Cavitation events reversibly disrupt the structure of the stratus corneum to allow transport of these large molecules. Other hormones and small proteins could also be delivered transdermally. Small chemotherapeutic molecules are delivered in research settings from micelles and liposomes exposed to ultrasound. Cavitation appears to play two roles: it disrupts the structure of the carrier vesicle and releases the drug; it also makes the cell membranes and capillaries more permeable to drugs. There remains a need to better understand the physics of cavitation of microbubbles and the impact that such cavitation has upon cells and drug-carrying vesicles. PMID:16296719

Pitt, William G.; Husseini, Ghaleb A.; Staples, Bryant J.

2006-01-01

97

Clinical aspects of drug delivery to tumors.  

PubMed

This report describes our experience on enhancement of drug delivery to solid tumors. Results of our preclinical and clinical studies including a randomized prospective phase III trial have validated the concept that enhanced drug delivery can significantly improve the treatment efficacy of intravesical mitomycin C therapy of superficial bladder cancer. The report further describes the roles of interstitial space, drug removal by capillaries, tissue structure and tissue composition on drug distribution. In general, drug distribution favors interstitial space and vasculature, with little penetration in muscles. The transport of highly protein-bound drugs such as paclitaxel and doxorubicin in a solid tumor is retarded by a high tumor cell density and enhanced by drug-induced apoptosis. Results of in vitro studies using solid tumor histocultures and in vivo studies using tumor-bearing animals demonstrate that the delivery of highly protein-bound drugs to tumor can be enhanced using a pretreatment that induces apoptosis and reduces cell density, and by using treatment schedules designed to take advantage of these drug-induced changes in tumor tissue composition. PMID:11772451

Au, Jessie L-S; Jang, Seong H; Wientjes, M Guill

2002-01-17

98

Ultrasonic-Activated Micellar Drug Delivery for Cancer Treatment  

PubMed Central

The use of nanoparticles and ultrasound in medicine continues to evolve. Great strides have been made in the areas of producing micelles, nanoemulsions and solid nanoparticles that can be used in drug delivery. An effective nanocarrier allows for the delivery of a high concentration of potent medications to targeted tissue while minimizing the side effect of the agent to the rest of the body. Polymeric micelles have been shown to encapsulate therapeutic agents and maintain their structural integrity at lower concentrations. Ultrasound is currently being used in drug delivery as well as diagnostics, and has many advantages that elevate its importance in drug delivery. The technique is non-invasive, thus no surgery is needed; the ultrasonic waves can be easily controlled by advanced electronic technology so that they can be focused on the desired target volume. Additionally, the physics of ultrasound are widely used and well understood; thus ultrasonic application can be tailored towards a particular drug delivery system. In this article, we review the recent progress made in research that utilizes both polymeric micelles and ultrasonic power in drug delivery. PMID:18506804

Husseini, Ghaleb A.; Pitt, William G.

2008-01-01

99

Nanoliposomal minocycline for ocular drug delivery  

PubMed Central

Nanoliposomal technology is a promising drug delivery system that could be employed to improve the pharmacokinetic properties of clearance and distribution in ocular drug delivery to the retina. We developed a nanoscale version of an anionic, cholesterol-fusing liposome that can encapsulate therapeutic levels of minocycline capable of drug delivery. We demonstrate that size extrusion followed by size-exclusion chromatography can form a stable 80-nm liposome that encapsulates minocycline at a concentration of 450 ± 30 ?M, which is 2% to 3% of loading material. More importantly, these nontoxic nanoliposomes can then deliver 40% of encapsulated minocycline to the retina after a subconjunctival injection in the STZ model of diabetes. Efficacy of therapeutic drug delivery was assessed via transcriptomic and proteomic biomarker panels. For both the free minocycline and encapsulated minocycline treatments, proinflammatory markers of diabetes were downregulated at both the messenger RNA and protein levels, validating the utility of biomarker panels for the assessment of ocular drug delivery vehicles. PMID:22465498

Kaiser, James M.; Imai, Hisanori; Haakenson, Jeremy K.; Brucklacher, Robert M.; Fox, Todd E.; Shanmugavelandy, Sriram S.; Unrath, Kellee A.; Pedersen, Michelle M.; Dai, Pingqi; Freeman, Willard M.; Bronson, Sarah K.; Gardner, Thomas W.; Kester, Mark

2012-01-01

100

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

101

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

102

Gastroretentive microparticles for drug delivery applications.  

PubMed

Many strategies have been proposed to explore the possibility of exploiting gastroretention for drug delivery. Such systems would be useful for local delivery, for drugs that are poorly soluble at higher pH or primarily absorbed from the proximal small intestine. Generally, the requirements of such strategies are that the vehicle maintains controlled drug release and exhibits prolonged residence time in the stomach. Despite widespread reporting of technologies, many have an inherent drawback of variability in transit times. Microparticulate systems, capable of distributing widely through the gastrointestinal tract, can potentially minimise this variation. While being retained in the stomach, the drug content is released slowly at a desired rate, resulting in reduced fluctuations in drug levels. This review summarises the promising role of microencapsulation in this field, exploring both floating and mucoadhesive microparticles and their application in the treatment of Helicobacter pylori, highlighting the clinical potential of eradication of this widespread infection. PMID:21726124

Adebisi, Adeola; Conway, Barbara R

2011-01-01

103

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

104

Drug Formulation / Drug Delivery Raj Suryanarayanan (Sury)  

E-print Network

for Lung CancerMagnetic Hyperthermia for Lung Cancerg yp gg yp g Department of DefenseDepartment of Defense Polymeric Systems for Cancer Prevention/TreatmentPolymeric Systems for Cancer Prevention/Treatment NCI of rodents Disease induction in animal models (e.g. cancer) #12;1. Drug solubilization through engineering

Blanchette, Robert A.

105

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

106

Insights into drug delivery across the nail plate barrier.  

PubMed

Abstract 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

107

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

108

Surface functionalized gold nanoparticles for drug delivery.  

PubMed

Gold nanoparticles have been widely explored as cancer therapeutics and diagnostic agents in recent years. With their unique subcellular size and good biocompatibility, gold nanoparticles are a promising drug delivery vehicle. In this study, folic acid-coated gold nanoparticles conjugated with fluorophore FITC through amine terminated poly(ethylene glycol) were prepared and confocal microscopy together with bright-field differential interference contrast imaging data showed that folic acid-coated gold nanoparticles accumulated mainly in cytoplasm of primary human fibroblasts, without causing any observable cytotoxicity upon exposure for 48 hours. Through the further development of a drug delivery system that conjugates doxorubicin onto the surface of gold nanoparticles with a poly(ethylene glycol) spacer via an SMCC linker, we demonstrated that multidrug resistance in cancer cells can be significantly overcome by a combination of highly efficient cellular entry and enhanced cytotoxicity of Au-SMCC-DOX nanoconjugates, as revealed both by confocal microscopy imaging and cytotoxicity assay. The prepared Au-SMCC-DOX nanoconjugates demonstrated enhanced drug accumulation and retention in multidrug resistant hepG2-R cancer cells when it was compared with free doxorubicin, with a cytoplasm accumulation profile. The results indicated that gold nanoparticles are a kind of promising drug delivery vehicle with good biocompatibility and suitable for further applications in drug delivery for improved chemotherapy, especially for overcoming multidrug resistance. PMID:23926802

Cheng, Jinping; Gu, Yan-Juan; Cheng, Shuk Han; Wong, Wing-Tak

2013-08-01

109

Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery.  

PubMed

The use of nanoparticulate pharmaceutical drug delivery systems (NDDSs) to enhance the in vivo effectiveness of drugs is now well established. The development of multifunctional and stimulus-sensitive NDDSs is an active area of current research. Such NDDSs can have long circulation times, target the site of the disease and enhance the intracellular delivery of a drug. This type of NDDS can also respond to local stimuli that are characteristic of the pathological site by, for example, releasing an entrapped drug or shedding a protective coating, thus facilitating the interaction between drug-loaded nanocarriers and target cells or tissues. In addition, imaging contrast moieties can be attached to these carriers to track their real-time biodistribution and accumulation in target cells or tissues. Here, I highlight recent developments with multifunctional and stimuli-sensitive NDDSs and their therapeutic potential for diseases including cancer, cardiovascular diseases and infectious diseases. PMID:25287120

Torchilin, Vladimir P

2014-11-01

110

Nano-Sized Carriers for Drug Delivery  

Microsoft Academic Search

Drug delivery is an important issue, especially with a new generation of therapeutics, which are either unstable in the biological\\u000a environment, have poor transport properties across biological membranes, are insoluble in water, or have very low bioavailability.\\u000a Nano-sized drug carriers can address some of the above issues and enhance their therapeutic efficacy. Different types of nano-sized\\u000a carriers, such as nanoparticles,

Sanjeeb K. Sahoo; Tapan K. Jain; Maram K. Reddy; Vinod Labhasetwar

111

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

112

Improved treatment of nicotine addiction and emerging pulmonary drug delivery.  

PubMed

Nicotine addiction remains the leading cause of death and disease in developed and developing nations and a major cause of mortality around the world. Currently, nicotine replacement therapies (NRTs), bupropion, and varenicline are approved by the regulatory agencies as first-line treatments for nicotine addiction. Emerging evidence indicates that varenicline and bupropion have some therapeutic limitations for treating nicotine addiction with oral route of administration. Thus, continued investigation of innovative drug delivery for nicotine addiction remains a critical priority. This review will discuss some novel strategies and future directions for pulmonary drug delivery, an emerging route of administration for smoking cessation. It is anticipated that the advancement of knowledge on pulmonary drug delivery will provide better management for nicotine addiction and other addictive disorders. PMID:22890202

Islam, Nazrul; Rahman, Shafiqur

2012-06-01

113

Ion Exchange Resins Transforming Drug Delivery Systems.  

PubMed

Ion-exchange resins are light, porous, three-dimensional high molecular weight cross -linked matrix of hydrocarbon chains carrying positively or negatively charged sites that can attract an ion of opposite charge from the surrounding medium. There is stoichiometric exchange of mobile ions between the solid and the solution called as Ion-exchange which does not lead to any radical change in the properties and structure of the solid. Depending upon the type of Ionexchanged it can be either Cation-exchange or Anion-exchange. They are prepared in the form of granules, beads or sheets. As drug delivery systems they have received considerable attention after the 1950s due to their inertness, freedom from side effects, high drug loading capacity, ease of sterilization and the fact that their structure can be easily altered to achieve the desired drug release characteristics. Their use is revolutionizing all traditional delivery systems namely- oral, nasal, ophthalmic and parenteral. Ion- exchange resins have been used for the development of novel drug delivery systems (NDDSs), to modify the characteristics of the dosage form and various other biomedical applications. The present article deals with the varied applications of ion-exchange resins for taste making, as resinates (simple and microencapsulated or coated), Pennkinetic systems, in selective recovery of pharmaceuticals, in pH and ionic strength responsive systems, in gastro-retentive systems, in hollow fiber systems, as sigmoidal release systems, as site specific delivery systems and as inotophoretically assisted transdermal drug delivery systems. They also have an immense importance when used as disintegrants/ superdisintegrants in formulation of orodispersible tablets, powder processing aids and in the dissolution and stabilization of drugs. PMID:20497105

Gupta, Shweta; Benien, Parul; Sahoo, P K

2010-05-24

114

Ion Exchange Resins Transforming Drug Delivery Systems.  

PubMed

Ion-exchange resins are light, porous, three-dimensional high molecular weight cross -linked matrix of hydrocarbon chains carrying positively or negatively charged sites that can attract an ion of opposite charge from the surrounding medium. There is stoichiometric exchange of mobile ions between the solid and the solution called as Ion-exchange which does not lead to any radical change in the properties and structure of the solid. Depending upon the type of Ion-exchanged it can be either Cation-exchange or Anion-exchange. They are prepared in the form of granules, beads or sheets. As drug delivery systems they have received considerable attention after the 1950s due to their inertness, freedom from side effects, high drug loading capacity, ease of sterilization and the fact that their structure can be easily altered to achieve the desired drug release characteristics. Their use is revolutionizing all traditional delivery systems namely- oral, nasal, ophthalmic and parenteral. Ion- exchange resins have been used for the development of novel drug delivery systems (NDDSs), to modify the characteristics of the dosage form and various other biomedical applications. The present article deals with the varied applications of ion-exchange resins for taste making, as resinates (simple and microencapsulated or coated), Pennkinetic systems, in selective recovery of pharmaceuticals, in pH and ionic strength responsive systems, in gastro-retentive systems, in hollow fiber systems, as sigmoidal release systems, as site specific delivery systems and as inotophoretically assisted transdermal drug delivery systems. They also have an immense importance when used as disintegrants / superdisintegrants in formulation of orodispersible tablets, powder processing aids and in the dissolution and stabilization of drugs. PMID:20158479

Gupta, Shweta; Parul; Sahoo, P K

2010-02-17

115

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

116

Proniosome based drug delivery system of piroxicam  

Microsoft Academic Search

Piroxicam is a widely used potent non-steroidal anti-inflammatory drug, with due potential for dermal delivery. Permeation of piroxicam from proniosome based reservoir type transdermal gel formulation across excised rat abdominal skin was investigated using Keshery Chein diffusion cell. There was considerable improvement in flux over the control gel formulation. The lipid vesicles were evaluated for entrapment efficiency and vesicle size

A. Chandra; P. K. Sharma

2008-01-01

117

REVIEW NANOPARTICLES IN DELIVERY OF CARDIOVASCULAR DRUGS  

Microsoft Academic Search

Everything in nature is built upward from the atomic level to define limits and structures to everything. Nanomedicines marked the field of medicine from nanobiotechnology, biological micro-electromechanical systems, microfluidics, biosensors, drug delivery, microarrays to tissue microengineering. Since then nanoparticles has overcome many challenges from blood brain barrier to targeting tumors. Where solid biodegradable nanoparticles were a step up liposome, targeting

M. SAEED ARAYNE; NAJMA SULTANA; FAIZA QURESHI

118

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

119

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

120

Intestinal lymphatic transport for drug delivery.  

PubMed

Intestinal lymphatic transport has been shown to be an absorptive pathway following oral administration of lipids and an increasing number of lipophilic drugs, which once absorbed, diffuse across the intestinal enterocyte and while in transit associate with secretable enterocyte lipoproteins. The chylomicron-associated drug is then secreted from the enterocyte into the lymphatic circulation, rather than the portal circulation, thus avoiding the metabolically-active liver, but still ultimately returning to the systemic circulation. Because of this parallel and potentially alternative absorptive pathway, first-pass metabolism can be reduced while increasing lymphatic drug exposure, which opens the potential for novel therapeutic modalities and allows the implementation of lipid-based drug delivery systems. This review discusses the physiological features of the lymphatics, enterocyte uptake and metabolism, links between drug transport and lipid digestion/re-acylation, experimental model (in vivo, in vitro, and in silico) of lymphatic transport, and the design of lipid- or prodrug-based drug delivery systems for enhancing lymphatic drug transport. PMID:21689702

Yáñez, Jaime A; Wang, Stephen W J; Knemeyer, Ian W; Wirth, Mark A; Alton, Kevin B

2011-09-10

121

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

122

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

123

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

124

Multiscale modeling of transdermal drug delivery  

NASA Astrophysics Data System (ADS)

This study addresses the modeling of transdermal diffusion of drugs, to better understand the permeation of molecules through the skin, and especially the stratum corneum, which forms the main permeation barrier of the skin. In transdermal delivery of systemic drugs, the drugs diffuse from a patch placed on the skin through the epidermis to the underlying blood vessels. The epidermis is the outermost layer of the skin and can be further divided into the stratum corneum (SC) and the viable epidermis layers. The SC consists of keratinous cells (corneocytes) embedded in the lipid multi-bilayers of the intercellular space. It is widely accepted that the barrier properties of the skin mostly arises from the ordered structure of the lipid bilayers. The diffusion path, at least for lipophilic molecules, seems to be mainly through the lipid bilayers. Despite the advantages of transdermal drug delivery compared to other drug delivery routes such as oral dosing and injections, the low percutaneous permeability of most compounds is a major difficulty in the wide application of transdermal drug delivery. In fact, many transdermal drug formulations include one or more permeation enhancers that increase the permeation of the drug significantly. During the last two decades, many researchers have studied percutaneous absorption of drugs both experimentally and theoretically. However, many are based on pharmacokinetic compartmental models, in which steady or pseudo-steady state conditions are assumed, with constant diffusivity and partitioning for single component systems. This study presents a framework for studying the multi-component diffusion of drugs coupled with enhancers through the skin by considering the microstructure of the stratum corneum (SC). A multiscale framework of modeling the transdermal diffusion of molecules is presented, by first calculating the microscopic diffusion coefficient in the lipid bilayers of the SC using molecular dynamics (MD). Then a homogenization procedure is performed over a model unit cell of the heterogeneous SC, resulting in effective diffusion parameters. These effective parameters are the macroscopic diffusion coefficients for the homogeneous medium that is "equivalent" to the heterogeneous SC, and thus can be used in finite element simulations of the macroscopic diffusion process.

Rim, Jee Eun

125

Revival of the abandoned therapeutic wortmannin by nanoparticle drug delivery.  

PubMed

One of the promises of nanoparticle (NP) carriers is the reformulation of promising therapeutics that have failed clinical development due to pharmacologic challenges. However, current nanomedicine research has been focused on the delivery of established and novel therapeutics. Here we demonstrate proof of the principle of using NPs to revive the clinical potential of abandoned compounds using wortmannin (Wtmn) as a model drug. Wtmn is a potent inhibitor of phosphatidylinositol 3' kinase-related kinases but failed clinical translation due to drug-delivery challenges. We engineered a NP formulation of Wtmn and demonstrated that NP Wtmn has higher solubility and lower toxicity compared with Wtmn. To establish the clinical translation potential of NP Wtmn, we evaluated the therapeutic as a radiosensitizer in vitro and in vivo. NP Wtmn was found to be a potent radiosensitizer and was significantly more effective than the commonly used radiosensitizer cisplatin in vitro in three cancer cell lines. The mechanism of action of NP Wtmn radiosensitization was found to be through the inhibition of DNA-dependent protein kinase phosphorylation. Finally, NP Wtmn was shown to be an effective radiosensitizer in vivo using two murine xenograft models of cancer. Our results demonstrate that NP drug-delivery systems can promote the readoption of abandoned drugs such as Wtmn by overcoming drug-delivery challenges. PMID:22547809

Karve, Shrirang; Werner, Michael E; Sukumar, Rohit; Cummings, Natalie D; Copp, Jonathan A; Wang, Edina C; Li, Chenxi; Sethi, Manish; Chen, Ronald C; Pacold, Michael E; Wang, Andrew Z

2012-05-22

126

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

127

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

128

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

129

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

130

Continuous On-Chip Micropumping for Microneedle Enhanced Drug Delivery  

Microsoft Academic Search

Microneedles are promising microfabricated devices for minimally invasive drug delivery applications. Needles can be integrated into a variety of devices. However, any portable drug delivery device with integrated microneedles will need an equally compact means to deliver therapeutics. This work presents microneedles integrated with an on-chip MEMS positive displacement micropump for continuous drug delivery applications. The generation and collapse of

Jeffrey D. Zahn; Ajay deshmukh; Albert P. Pisano; Dorian Liepmann

2004-01-01

131

Liposomes and Niosomes as Topical Drug Delivery Systems  

Microsoft Academic Search

The skin acts as a major target as well as a principle barrier for topical\\/transdermal (TT) drug delivery. The stratum corneum plays a crucial role in barrier function for TT drug delivery. Despite major research and development efforts in TT systems and the advantages of these routes, low stratum corneum permeability limits the usefulness of topical drug delivery. To overcome

M. J. Choi; H. I. Maibach

2005-01-01

132

Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging  

Microsoft Academic Search

Drug delivery is an interdisciplinary and independent field of research and is gaining the attention of pharmaceutical researchers, medical doctors and industry. A safe and targeted drug delivery could improve the performance of some classic medicines already on the market, and moreover, will have implications for the development and success of new therapeutic strategies such as anticancer drug delivery, peptide

Suphiya Parveen; Ranjita Misra; Sanjeeb K. Sahoo

133

BASIC INVESTIGATIONS Ultrasound-Enhanced Transcorneal Drug Delivery  

E-print Network

of transdermal drug delivery.8 Im- provement of as much as 1000-fold was achieved in the deliv- eryBASIC 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

Clark, John

134

Bharatbook.com - Drug Delivery Systems forecasts for 2012 & 2017  

Microsoft Academic Search

Oral drug delivery systems will remain the largest method used for drug delivery. Orally disintegrating tablets and transmucosal drugs will generate strong growth opportunities in the delivery of pain control and other critical care medication. Ease of administration advantages will promote the widening use of chewable tablet dosages for nutritional, respiratory and central nervous system agents, especially pediatric preparations. Better

2008-01-01

135

Zein in controlled drug delivery and tissue engineering.  

PubMed

Controlled delivery of a bioactive to specific organ, cellular and sub-cellular level is a desired feature of a drug carrier system. In order to achieve this goal, formulation scientists search for better alternatives of biomaterials to deliver the therapeutics in more precise and controlled manner in vivo. Zein, a plant protein obtained from corn, is a useful biomaterial for several industrial applications including agriculture, cosmetics, packaging and pharmaceuticals. Being a hydrophobic protein, which is biodegradable, biocompatible, economic to use and with generally regarded safe "GRAS" status, it is an attractive biomaterial for human use. Novel biomedical applications of zein such as controlled and targeted delivery of bioactives and tissue engineering are the current research interests of the scientific fraternity. Here we attempt to review the literature on zein as a biopolymer for drug/vaccine/gene delivery and its applicability in tissue engineering. PMID:24993426

Paliwal, Rishi; Palakurthi, Srinath

2014-09-10

136

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

137

Local Inner Ear Drug Delivery and Pharmacokinetics  

PubMed Central

Summary A number of drugs are in widespread clinical use for the treatment of inner ear disorders by applying them directly to the inner ear. Many new substances and drug delivery systems specific to the inner ear are under development, and in some cases are undergoing evaluations in animal experiments and in clinical studies. The pharmacokinetics of drugs in the inner ear, however, is not well defined and the field is plagued by technical problems in obtaining pure samples of the inner ear fluids for analysis. Nevertheless, a basic understanding of the mechanisms of drug dispersal in the inner ear has emerged that facilitates the design and interpretation of future pharmacokinetic studies. PMID:16214674

Salt, Alec N.; Plontke, Stefan K.R.

2008-01-01

138

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

139

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

140

Floating drug delivery systems for prolonging gastric residence time: a review.  

PubMed

Oral delivery of the drug is the most preferable route of drug delivery due to the ease of administration, patient compliance and flexibility in the formulations. Recent technological advancements have been made in controlled oral drug delivery systems by overcoming physiological difficulties, such as short gastric residence time and highly variable gastric emptying time. Gastroretentive dosage forms have been designed over the past three decades to overcome these difficulties. Several technical approaches are currently utilized in the prolongation of gastric residence time, including highdensity, swelling and expanding, polymeric mucoadhesive, ion-exchange, raft forming, magnetic and floating drug delivery systems (FDDS), as well as other delayed gastric emptying devices. In this review, the current technological developments of FDDS including patented delivery systems and marketed products, and their advantages and future potential for oral controlled drug delivery are discussed. PMID:21696354

Sathish, D; Himabindu, S; Kumar, Y Shravan; Shayeda; Rao, Y Madhusudan

2011-09-01

141

75 FR 45640 - Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...  

Federal Register 2010, 2011, 2012, 2013

...Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...industry entitled ``Residual Drug in Transdermal and Related Drug Delivery Systems...developers and manufacturers of transdermal drug delivery systems...

2010-08-03

142

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

143

Pulmonary drug delivery: Implication for new strategy for pharmacotherapy for neurodegenerative disorders.  

PubMed

Innovative drug delivery in the treatment of brain neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD) has the potential to avoid many unwanted side effects over current medications. Advances in understanding of these diseases and their treatments have led to the search for novel modes of drug delivery. In this review, we have highlighted new strategies and future prospects for pulmonary delivery of drugs for the management of these important neurological disorders. The advancement of knowledge on pulmonary drug delivery will provide novel therapeutic formulations for better management of the PD and AD patients throughout the world. PMID:22504719

Islam, N; Rahman, S

2008-10-01

144

Biosimilar drugs: Current status  

PubMed Central

Biologic products are being developed over the past three decades. The expiry of patent protection for many biological medicines has led to the development of biosimilars in UK or follow on biologics in USA. This article reviews the literature on biosimilar drugs that covers the therapeutic status and regulatory guidelines. Appraisal of published articles from peer reviewed journals for English language publications, search from PubMed, and guidelines from European Medicines Agency, US Food Drug Administration (FDA) and India were used to identify data for review. Literature suggest that biosimilars are similar biological products, i.e., comparable but not identical to the reference product, are not generic version of innovator product and do not ensure therapeutic equivalence. Biosimilars present more challenges than conventional generics and marketing approval is also more complicated. To improve access, US Congress passed the Biologics Price Competition and Innovation act 2009 and US FDA allowed “abbreviated pathway” for their approval. U.S law has defined new standards and terms and EMA scientific guidelines have also set detailed approval standards. India being one of the most preferred manufacturing destinations of biosimilars, there is a need for stringent safety and regulatory guidelines. The New India Guidelines “Draft Guidelines on Similar Biologics were announced in June 2012, by Department of Biotechnology at Boston bio and available online. PMID:25143877

Kumar, Rajiv; Singh, Jagjit

2014-01-01

145

Biosimilar drugs: Current status.  

PubMed

Biologic products are being developed over the past three decades. The expiry of patent protection for many biological medicines has led to the development of biosimilars in UK or follow on biologics in USA. This article reviews the literature on biosimilar drugs that covers the therapeutic status and regulatory guidelines. Appraisal of published articles from peer reviewed journals for English language publications, search from PubMed, and guidelines from European Medicines Agency, US Food Drug Administration (FDA) and India were used to identify data for review. Literature suggest that biosimilars are similar biological products, i.e., comparable but not identical to the reference product, are not generic version of innovator product and do not ensure therapeutic equivalence. Biosimilars present more challenges than conventional generics and marketing approval is also more complicated. To improve access, US Congress passed the Biologics Price Competition and Innovation act 2009 and US FDA allowed "abbreviated pathway" for their approval. U.S law has defined new standards and terms and EMA scientific guidelines have also set detailed approval standards. India being one of the most preferred manufacturing destinations of biosimilars, there is a need for stringent safety and regulatory guidelines. The New India Guidelines "Draft Guidelines on Similar Biologics were announced in June 2012, by Department of Biotechnology at Boston bio and available online. PMID:25143877

Kumar, Rajiv; Singh, Jagjit

2014-07-01

146

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

147

Drug delivery strategies for the treatment of malignant gliomas.  

PubMed

As primary brain tumors, malignant gliomas are known to be one of the most insidious types of brain cancer afflicting the humans. The current standard strategy for the treatment of malignant gliomas includes the surgical resection of the tumor when possible, followed by a combination of radiotherapy and/or a certain chemotherapeutic protocol. However, due to the short mean survival, frequent recurrences, and poor prognosis associated with the tumors, new therapeutic strategies are investigated consecutively. These novel drug delivery approaches can be subdivided as systemic and local drug administration. This review focuses on localized drug delivery strategies for the treatment of malignant gliomas, including the injections, infusions, trans-nasal delivery systems, convection enhanced delivery (CED) systems, and various types of polymeric implants. Furthermore, systemic strategies to increase the drug penetration into the brain, such as temporary disruption of the blood brain barrier (BBB), chemical modification of the available therapeutic substances, and utilization of endogenous transport systems will be briefly discussed. PMID:22721856

Allhenn, Daniela; Boushehri, Maryam Alsadat Shetab; Lamprecht, Alf

2012-10-15

148

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

149

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 mother or fetus...

Audus, Kenneth L.

1999-01-01

150

A resorbable polymeric microreservoir device for controlled release drug delivery  

E-print Network

The method by which a drug is delivered can have a significant effect on the drug's therapeutic efficacy. Pulsatile delivery of certain drugs and molecules (such as hormones) has been shown to more efficacious than continuous ...

Grayson, Amy Catherine Richards, 1975-

2003-01-01

151

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 targeting; cancer nanomedicine; micelle pharmacokinetics; polymer micelles; responsive drug release with greatly improved drug pharmacokinetics and efficacious response in cancer treatment. Typical

Gao, Jinming

152

In Vitro Performance Testing for Pulmonary Drug Delivery  

Microsoft Academic Search

\\u000a This chapter provides a detailed review of in vitro testing methods for inhalation products. Specifically, the current compendial\\u000a methods for pulmonary drug delivery are presented, discussion of cascade impactor use and simplification, determination of\\u000a aerosol electrostatics, static characterization of particles and powders, solubility screening, and a review of research leading\\u000a to improved dissolution studies for these products.

Yoen-Ju Son; Jolyon P. Mitchell; Jason T. McConville

153

Targeted delivery of drugs for liver fibrosis.  

PubMed

Liver fibrosis and its end stage disease cirrhosis are a major cause of mortality and morbidity around the world. There is no effective pharmaceutical intervention for liver fibrosis at present. Many drugs that show potent antifibrotic activities in vitro often show only minor effects in vivo because of insufficient concentrations of drugs accumulating around the target cell and their adverse effects as a result of affecting other non-target cells. Hepatic stellate cells (HSC) play a critical role in the fibrogenesis of liver, so they are the target cells of antifibrotic therapy. Several kinds of targeted delivery system that could target the receptors expressed on HSC have been designed, and have shown an attractive targeted potential in vivo. After being carried by these delivery systems, many agents showed a powerful antifibrotic effect in animal models of liver fibrosis. These targeted delivery systems provide a new pathway for the therapy of liver fibrosis. The characteristics of theses targeted carriers are reviewed in this paper. PMID:19413460

Li, Feng; Wang, Ji-yao

2009-05-01

154

Thermosensitive liposomal drug delivery systems: state of the art review  

PubMed Central

Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or high intensity focused ultrasound. In vivo results have demonstrated strong evidence that external targeting is superior over passive targeting achieved by highly stable long-circulating drug formulations like PEGylated liposomal doxorubicin. Up to March 2014, the Web of Science listed 371 original papers in this field, with 45 in 2013 alone. Several formulations have been developed since 1978, with lysolipid-containing, low temperature-sensitive liposomes currently under clinical investigation. This review summarizes the historical development and effects of particular phospholipids and surfactants on the biophysical properties and in vivo efficacy of thermosensitive liposome formulations. Further, treatment strategies for solid tumors are discussed. Here we focus on temperature-triggered intravascular and interstitial drug release. Drug delivery guided by magnetic resonance imaging further adds the possibility of performing online monitoring of a heating focus to calculate locally released drug concentrations and to externally control drug release by steering the heating volume and power. The combination of external targeting with thermosensitive liposomes and magnetic resonance-guided drug delivery will be the unique characteristic of this nanotechnology approach in medicine.

Kneidl, Barbara; Peller, Michael; Winter, Gerhard; Lindner, Lars H; Hossann, Martin

2014-01-01

155

DISSOLVABLE-TIPPED, DRUG-RESERVOIR INTEGRATED MICRONEEDLE ARRAY FOR TRANSDERMAL DRUG DELIVERY  

E-print Network

DISSOLVABLE-TIPPED, DRUG-RESERVOIR INTEGRATED MICRONEEDLE ARRAY FOR TRANSDERMAL DRUG DELIVERY Seung array for transdermal drug delivery. The hydrogel-based dissolvable tips are formed in a reusable. INTRODUCTION Microneedles are attractive tools for transdermal drug-delivery and vaccination due

156

Photocrosslinked DNA nanospheres for drug delivery.  

PubMed

DNA has been employed as both a genetic and a generic material. X-shaped DNA (X-DNA) in particular has four branched arms, providing multivalent functionalities that can allow for simultaneous multiple crosslinking. Here we report the synthesis of four acrylate-functionalized X-DNA monomers that can be further photocrosslinked to form monodisperse and tunable DNA nanospheres. In particular, the size and surface charge of these nanospheres were precisely controlled in a linear fashion, simply by tuning the monomer concentration in the reaction. The morphology and surface properties of the nanospheres were characterized using FT-IR, HPLC, TEM, AFM, zeta potential, and DLS analysis. In vitro studies in mammalian cells revealed that these DNA nanospheres demonstrated significant efficacy in the delivery of doxorubicin. These results highlight the potential of using DNA as material building blocks to design novel nanocarriers with properties tailored for the delivery of drugs in general and DNA/RNA in particular. PMID:21590877

Roh, Young Hoon; Lee, Jong Bum; Tan, Shawn J; Kim, Bojeong; Park, Hyeongsu; Rice, Edward J; Luo, Dan

2010-07-01

157

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

158

CCMR: Controlled Drug Delivery from New Biomaterials  

NSDL National Science Digital Library

Fabrication of new biomaterials for drug delivery has a great impact on todayâs industries and developments. The improvement of efficiency and control of this process can benefit every human being, thus requires a complete understanding of all behavior related to these processes. Our main objective was to synthesize biodegradable polyesters based on dihydroxyacetone dimer and sebacic acid. It was also of our concern to characterize this polymer through different methods such as 1H-NMR and GPC to establish the material properties. Optimization of this synthesis was based on variations of different parameters in order to obtain the most desirable properties for the material.

Pelet, Jeisa

2005-08-17

159

Importance of novel drug delivery systems in herbal medicines  

PubMed Central

Novel drug delivery system is a novel approach to drug delivery that addresses the limitations of the traditional drug delivery systems. Our country has a vast knowledge base of Ayurveda whose potential is only being realized in the recent years. However, the drug delivery system used for administering the herbal medicine to the patient is traditional and out-of-date, resulting in reduced efficacy of the drug. If the novel drug delivery technology is applied in herbal medicine, it may help in increasing the efficacy and reducing the side effects of various herbal compounds and herbs. This is the basic idea behind incorporating novel method of drug delivery in herbal medicines. Thus it is important to integrate novel drug delivery system and Indian Ayurvedic medicines to combat more serious diseases. For a long time herbal medicines were not considered for development as novel formulations owing to lack of scientific justification and processing difficulties, such as standardization, extraction and identification of individual drug components in complex polyherbal systems. However, modern phytopharmaceutical research can solve the scientific needs (such as determination of pharmacokinetics, mechanism of action, site of action, accurate dose required etc.) of herbal medicines to be incorporated in novel drug delivery system, such as nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, solid lipid nanoparticles and so on. This article summarizes various drug delivery technologies, which can be used for herbal actives together with some examples. PMID:22228938

Devi, V. Kusum; Jain, Nimisha; Valli, Kusum S.

2010-01-01

160

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

161

Interfacial kinetics effects on transdermal drug delivery: a computer modeling  

E-print Network

Interfacial kinetics effects on transdermal drug delivery: a computer modeling Malcolm M. Q. Xing1 a transdermal drug delivery process. A more realistic multilayer structure, including the patch, SC and viable words: transdermal drug ­ interphase barrier ­ multi- layer finite-element model ­ contact transfer

Pan, Ning

162

Antibody Drug Conjugate Bioinformatics: Drug Delivery through the Letterbox  

PubMed Central

Antibodies appear to be the first line of defence in the adaptive immune response of vertebrates and thereby are involved in a multitude of biochemical mechanisms, such as regulation of infection, autoimmunity, and cancer. It goes without saying that a full understanding of antibody function is required for the development of novel antibody-interacting drugs. These drugs are the Antibody Drug Conjugates (ADCs), which are a new type of targeted therapy, used for example for cancer. They consist of an antibody (or antibody fragment such as a single-chain variable fragment [scFv]) linked to a payload drug (often cytotoxic). Because of the targeting, the side effects should be lower and give a wider therapeutic window. Overall, the underlying principle of ADCs is to discern the delivery of a drug that is cytotoxic to a target that is cancerous, hoping to increase the antitumoural potency of the original drug by reducing adverse effects and side effects, such as toxicity of the cancer target. This is a pioneering field that employs state-of-the-art computational and molecular biology methods in the fight against cancer using ADCs. PMID:23853668

Vlachakis, Dimitrios

2013-01-01

163

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

164

Polymeric micelles for acyclovir drug delivery.  

PubMed

Polymeric prodrug micelles for delivery of acyclovir (ACV) were synthesized. First, ACV was used directly to initiate ring-opening polymerization of ?-caprolactone to form ACV-polycaprolactone (ACV-PCL). Through conjugation of hydrophobic ACV-PCL with hydrophilic methoxy poly(ethylene glycol) (MPEG) or chitosan, polymeric micelles for drug delivery were formed. (1)H NMR, FTIR, and gel permeation chromatography were employed to show successful conjugation of MPEG or chitosan to hydrophobic ACV-PCL. Through dynamic light scattering, zeta potential analysis, transmission electron microscopy, and critical micelle concentration (CMC), the synthesized ACV-tagged polymeric micelles were characterized. It was found that the average size of the polymeric micelles was under 200nm and the CMCs of ACV-PCL-MPEG and ACV-PCL-chitosan were 2.0mgL(-1) and 6.6mgL(-1), respectively. The drug release kinetics of ACV was investigated and cytotoxicity assay demonstrates that ACV-tagged polymeric micelles were non-toxic. PMID:25193154

Sawdon, Alicia J; Peng, Ching-An

2014-10-01

165

Vaults Engineered for Hydrophobic Drug Delivery  

PubMed Central

The vault nanoparticle is one of the largest known ribonucleoprotein complexes in the sub-100 nm range. Highly conserved and almost ubiquitously expressed in eukaryotes, vaults form a large nanocapsule with a barrel-shaped morphology surrounding a large hollow interior. These properties make vaults an ideal candidate for development into a drug delivery vehicle. In this study, we report the first example of using vaults towards this goal. We engineered recombinant vaults to encapsulate the highly insoluble and toxic hydrophobic compound All-trans Retinoic Acid (ATRA) using a vault binding lipoprotein complex that forms a lipid bilayer nanodisk. These recombinant vaults offer protection to the encapsulated ATRA from external elements. Furthermore, a cryo-electron tomography (cryo-ET) reconstruction shows the vault binding lipoprotein complex sequestered within the vault lumen. Finally, these ATRA loaded vaults have enhanced cytotoxicity against the hepatocellular carcinoma cell line HepG2. The ability to package therapeutic compounds into the vault is an important achievement toward their development into a viable and versatile platform for drug delivery. PMID:21506266

Buehler, Daniel C.; Toso, Daniel B.; Kickhoefer, Valerie A.; Zhou, Z. Hong

2013-01-01

166

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

167

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

168

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

169

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

170

Transdermal microconduits by microscission for drug delivery and sample acquisition  

E-print Network

Background Painless, rapid, controlled, minimally invasive molecular transport across human skin for drug delivery and analyte acquisition is of widespread interest. Creation of microconduits through the stratum corneum ...

Gonzalez, Salvador

171

Enhancing pharmaceutical formulations to improve efficacy and delivery of drug molecules  

E-print Network

Major impediments to the full utility of current and potential drugs include issues of resistance and delivery. To address these challenges, in this thesis two directions of research were pursued: (1) the use of multivalent ...

Weight, Alisha K. (Alisha Kessel)

2013-01-01

172

Design of a multiple drug delivery system directed at periodontitis.  

PubMed

Periodontal disease is highly prevalent, with 90% of the world population affected by either periodontitis or its preceding condition, gingivitis. These conditions are caused by bacterial biofilms on teeth, which stimulate a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The present research sought to demonstrate development of a multiple drug delivery system for stepwise treatment of different stages of periodontal disease. More specifically, multilayered films were fabricated from an association polymer comprising cellulose acetate phthalate and Pluronic F-127 to achieve sequential release of drugs. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. Different erosion times and adjustable sequential release profiles were achieved by modifying the number of layers or by inclusion of a slower-eroding polymer layer. Analysis of antibiotic and anti-inflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. The multilayered CAPP delivery system offers a versatile approach for releasing different drugs based on the pathogenesis of periodontitis and other conditions. PMID:23948165

Sundararaj, Sharath C; Thomas, Mark V; Peyyala, Rebecca; Dziubla, Thomas D; Puleo, David A

2013-11-01

173

Design of a Multiple Drug Delivery System Directed at Periodontitis  

PubMed Central

Periodontal disease is highly prevalent, with 90% of the world population affected by either periodontitis or its preceding condition, gingivitis. These conditions are caused by bacterial biofilms on teeth, which stimulate a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The present research sought to demonstrate development of a multiple drug delivery system for stepwise treatment of different stages of periodontal disease. More specifically, multilayered films were fabricated from an association polymer comprising cellulose acetate phthalate and Pluronic F-127 to achieve sequential release of drugs. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. Different erosion times and adjustable sequential release profiles were achieved by modifying the number of layers or by inclusion of a slower-eroding polymer layer. Analysis of antibiotic and anti-inflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. The multilayered CAPP delivery system offers a versatile approach for releasing different drugs based on the pathogenesis of periodontitis and other conditions. PMID:23948165

Sundararaj, Sharath C.; Thomas, Mark V.; Peyyala, Rebecca; Dziubla, Thomas D.; Puleo, David A.

2013-01-01

174

Microencapsulation: A promising technique for controlled drug delivery  

PubMed Central

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.

2010-01-01

175

Automated modular synthesis of aptamer-drug conjugates for targeted drug delivery.  

PubMed

Aptamer-drug conjugates (ApDCs) are promising targeted drug delivery systems for reducing toxicity while increasing the efficacy of chemotherapy. However, current ApDC technologies suffer from problems caused by the complicated preparation and low controllability of drug-aptamer conjugation. To solve such problems, we have designed and synthesized a therapeutic module for solid phase synthesis, which is a phosphoramdite containing an anticancer drug moiety and a photocleavable linker. Using this module, we have realized automated and modular synthesis of ApDCs, and multiple drugs were efficiently incorporated into ApDCs at predesigned positions. The ApDCs not only recognize target cancer cells specifically, but also release drugs in a photocontrollable manner. We demonstrated the potential of automated and modular ApDC technology for applications in targeted cancer therapy. PMID:24483627

Wang, RuoWen; Zhu, Guizhi; Mei, Lei; Xie, Yan; Ma, Haibin; Ye, Mao; Qing, Feng-Ling; Tan, Weihong

2014-02-19

176

Extended Release Drug Delivery Strategies in Psychiatry  

PubMed Central

Objective: An overview of the emerging field of long-term delivery strategies for improved convenience and adherence with psychiatric medications is provided. This review is motivated by the hypothesis that adherence to treatment is an important determinant of clinical outcomes in a wide range of settings and is particularly important in psychiatry practice where patients require treatment for months or years and premature discontinuation can have serious consequences for patient health and quality of life. Design: The author reviews the relevant literature and highlights several approaches to providing improved access to continuous medication through new and innovative delivery strategies ranging from days to annual intervals. Benefits and Disadvantages: Several solutions to the problem of discontinuous access to pharmacotherapy are being developed in the form of new, long-acting drug-delivery systems, which gradually release medication over a period of several days or weeks with a single application. Long-acting formulations of psychiatric medications offer a number of potential benefits in comparison with conventional immediate-release agents, including improved safety and effectiveness. Potential limitations to using long-acting formulations may include pain and discomfort at the injection site, perceived inconvenience of a new treatment method, preference for oral medications, and length of time to titrate down to the lowest effective dose. Conclusions: The introduction of new, long-acting drug formulations could provide significant improvements in clinical outcomes and patient satisfaction for many patients, including those with affective disorders, schizophrenia, and alcohol dependence. Switching from oral administration to these new agents requires careful monitoring to reach the optimal dose, and patient concerns regarding the use of new delivery methods must be addressed. Long-acting formulations are not intended to be a sole form of treatment, and the use of psychotherapy as an adjunct form of treatment is still required. Controlled clinical trials of these new formulations have only recently been completed, offering clinicians a new option in their treatment regimens; however, as technologies improve, several new formulations are likely to enter clinical trials during the next few years. Psychiatrists will need to become acquainted with these technologies and educate their patients about them so they may work together to determine the most effective treatment option. PMID:21152152

2005-01-01

177

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

178

Experimental strategies for investigating passive and ultrasound-enhanced transdermal drug delivery  

E-print Network

Transdermal drug delivery offers many advantages over traditional drug delivery methods. However, the natural resistance of the skin to drug permeation represents a major challenge that transdermal drug delivery needs to ...

Seto, Jennifer Elizabeth

2011-01-01

179

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

180

Prodrug and conjugate drug delivery strategies for improving HIV/AIDS therapy  

PubMed Central

Despite the wide variety of highly potent anti-HIV drugs that have been developed and made available in clinical practice over the years, eradication of HIV infection has not been achieved. Currently, HIV infection and AIDS are thought to be chronically treatable. HIV attacks host immune cells namely macrophages and CD4+T-cells and sequesters itself into sanctuary and reservoir sites such as the lymphoid tissues, testes, and brain. Initial drug delivery efforts with prodrugs and drug conjugates focused on improving the physicochemical (i.e. solubility), biopharmaceutic (i.e. absorption, metabolism), and pharmacokinetic (i.e. blood concentrations) properties of the parent drugs. Eradicating HIV, however, will require advanced drug delivery approaches in order to access and maintain effective drug concentrations for prolonged periods of time in sanctuary sites. The current review discusses prodrug/conjugate efforts, clinical successes and describes drug delivery challenges and approaches for eradicating HIV infection. PMID:20717488

Palombo, M.S.; Singh, Y.; Sinko, P.J.

2009-01-01

181

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

182

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

183

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

184

Herbal Excipients in Novel Drug Delivery Systems  

PubMed Central

The use of natural excipients to deliver the bioactive agents has been hampered by the synthetic materials. However advantages offered by these natural excipients are their being non-toxic, less expensive and freely available. The performance of the excipients partly determines the quality of the medicines. The traditional concept of the excipients as any component other than the active substance has undergone a substantial evolution from an inert and cheap vehicle to an essential constituent of the formulation. Excipients are any component other than the active substance(s) intentionally added to formulation of a dosage form. This article gives an overview of herbal excipients which are used in conventional dosage forms as well as novel drug delivery systems. PMID:20046764

Shirwaikar, A.; Shirwaikar, Annie; Prabu, S. Lakshmana; Kumar, G. Aravind

2008-01-01

185

Kontrollierte therapeutische Systeme (Controlled drug delivery systems)  

NASA Astrophysics Data System (ADS)

Es gibt eine grosse Anzahl von Arzneistoffen, die nicht mit der höchsten Effizienz eingesetzt werden können, weil das geeignete therapeutische System (drug delivery system) für die optimale Applikation fehlt. Viele Arzneistoffe setzen eine häufige Anwendung voraus und sind oft mit mehr oder weniger starken Nebenwirkungen oder aber mit Beeinträchtigungen von Arbeits- und Lebensrhythmus der Patienten verbunden. Der therapeutische Erfolg einer medikamentösen Behandlung setzt eine korrekte Diagnose, die Wahl der richtigen Wirksubstanz sowie ihr Vorliegen in geeigneter Darreichungsform voraus. Zudem muss ein genauer Verabreichungsplan erstellt werden, dessen Einhaltung seitens der Patienten eine wesentliche Voraussetzung für die optimale Wirkung des Arzneistoffes ist. Das Mass, mit dem eine Wirksubstanz therapeutisch voll genutzt werden kann, korreliert direkt mit der Darreichungsform, in der sie angewandt wird. Da viele hochwirksame Arzneimittel bereits existieren, hat sich, neben Neuentwicklungen, das Interesse im vergangenen Jahrzehnt der Optimierung von Arzneimittelwirkungen durch neue Darreichungsformen zugewandt.

Ha, Suk-Woo; Wintermantel, Erich

186

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

187

Preactivated thiomers for vaginal drug delivery vehicles.  

PubMed

It was the purpose of this study to design and evaluate a chitosan derivative as mucoadhesive excipient for vaginal drug delivery systems. The chemical modification of chitosan was achieved by conjugation of thioglycolic acid (TGA) resulting in 1594 ?mol thiol groups per gram of polymer followed by the linkage of mercaptonicotinic acid (MNA) to the immobilized thiol groups via disulfide bonding leading to 702 ?mol ligand per gram of preactivated polymer. The mucoadhesive properties of these polymers within newly designed vaginal formulations (Chitosan-TGA and Chitosan-TGA-MNA) and commercially available vaginal formulations (Candibene®, Daktarin®, Dalacin®, GynoPevaryl®) were tested over a time period of 24 h via a mucoadhesion test system simulating vaginal conditions, tensile studies and mucus polymer interaction studies via viscosity measurements. Within the vaginal test system simulating vaginal in situ conditions, a 1.5-fold increase in mucoadhesion could be observed for preactivated thiomer formulations after 24 h in comparison to commercially available formulations. Similar results were achieved for tensile studies, as the chitosan-TGA-MNA containing formulation resulted in a 4.9-fold increase in total work of adhesion (TWA) in comparison to Candibene which showed the highest TWA value of all tested commercial formulations. Also in terms of rheology investigations of mucus/formulation mixtures, a 5.8-fold increase in dynamic viscosity for chitosan-TGA-MNA containing mixtures could be observed in comparison to the mucus-free control. In contrast, commercially available formulations achieved a maximum enhancement of 1.9-fold. These outcomes confirm that the newly developed polymer is a promising tool for vaginal drug delivery likely providing a prolonged vaginal residence time due to its comparatively high mucoadhesive properties. PMID:23886732

Friedl, Heike E; Dünnhaupt, Sarah; Waldner, Claudia; Bernkop-Schnürch, Andreas

2013-10-01

188

The Benefits and Challenges Associated with the Use of Drug Delivery Systems in Cancer Therapy  

PubMed Central

The use of Drug Delivery Systems as nanocarriers for chemotherapeutic agents can improve the pharmacological properties of drugs by altering drug pharmacokinetics and biodistribution. Among the many drug delivery systems available, both micelles and liposomes have gained the most attention in recent years due to their clinical success. There are several formulations of these nanocarrier systems in various stages of clinical trials, as well as currently clinically approved liposomal-based drugs. In this review, we discuss these drug carrier systems, as well as current efforts that are being made in order to further improve their delivery efficacy through the incorporation of targeting ligands. In addition, this review discusses aspects of drug resistance attributed to the remodeling of the extracellular matrix that occurs during tumor development and progression, as well as to the acidic, hypoxic, and glucose deprived tumor microenvironment. Finally, we address future prospective approaches to overcoming drug resistance by further modifications made to these drug delivery systems, as well as the possibility of coencapsulation/coadministration of various drugs aimed to surmount some of these microenvironmental-influenced obstacles for efficacious drug delivery in chemotherapy. PMID:20417189

Cukierman, Edna; Khan, David R.

2010-01-01

189

Oral Drug Delivery with Polymeric Nanoparticles: The Gastrointestinal Mucus Barriers  

PubMed Central

Oral delivery is the most common method for drug administration. However, poor solubility, stability, and bioavailability of many drugs make achieving therapeutic levels via the gastrointestinal (GI) tract challenging. Drug delivery must overcome numerous hurdles, including the acidic gastric environment and the continuous secretion of mucus that protects the GI tract. Nanoparticle drug carriers that can shield drugs from degradation and deliver them to intended sites within the GI tract may enable more efficient and sustained drug delivery. However, the rapid secretion and shedding of GI tract mucus can significantly limit the effectiveness of nanoparticle drug delivery systems. Many types of nanoparticles are efficiently trapped in and rapidly removed by mucus, making controlled release in the GI tract difficult. This review addresses the protective barrier properties of mucus secretions, how mucus affects the fate of orally administered nanoparticles, and recent developments in nanoparticles engineered to penetrate the mucus barrier. PMID:22212900

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

2012-01-01

190

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

191

Synergistic Effect of Enhancers for Transdermal Drug Delivery  

Microsoft Academic Search

Transdermal drug delivery offers a non-invasive route of drug administration, although its applications are limited by low skin permeability. Various enhancers including iontophoresis, chemicals, ultrasound, and electroporation have been shown to enhance transdermal drug transport. Although all these meth- ods have been individually shown to enhance transdermal drug transport, their combinations have often been found to enhance transdermal transport more

Samir Mitragotri

2000-01-01

192

Hollow Microneedle Arrays for Intradermal Drug Delivery and DNA Electroporation  

E-print Network

Hollow Microneedle Arrays for Intradermal Drug Delivery and DNA Electroporation Lie´vin Daugimont of microneedles with electric pulses causing electroporation could result in an efficient and less painful delivery of drugs and DNA into the skin. Hollow conductive microneedles were used for (1) needle- free

Ljubljana, University of

193

Scanning probe microscopy in the field of drug delivery  

Microsoft Academic Search

The scanning probe microscopes (SPMs) are a group of powerful surface sensitive instruments which when used complimentarily with traditional analytical techniques can provide invaluable, definitive information aiding our understanding and development of drug delivery systems. In this review, the main use of the SPMs (particularly the atomic force microscopy (AFM)) and their successes in forwarding drug delivery are highlighted and

Ya Tsz A. Turner; Clive J. Roberts; Martyn C. Davies

2007-01-01

194

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

195

A practical assessment of transdermal drug delivery by skin electroporation  

Microsoft Academic Search

Transdermal drug delivery has many potential advantages, but the skin's poorly-permeable stratum corneum blocks delivery of most drugs at therapeutic levels. Short high-voltage pulses have been used to electroporate the skin's lipid bilayer barriers and thereby deliver compounds at rates increased by as much as four orders of magnitude. Evidence that the observed flux enhancement is due to physical alteration

Mark R Prausnitz

1999-01-01

196

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

197

Pharmacosomes: An Emerging Novel Vesicular Drug Delivery System for Poorly Soluble Synthetic and Herbal Drugs  

PubMed Central

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

2013-01-01

198

Supramolecular Polymers Based on Cyclodextrins for Drug and Gene Delivery  

Microsoft Academic Search

\\u000a Supramolecular polymers based on cyclodextrins (CDs) have inspired interesting and rapid developments as novel biomaterials\\u000a in a broad range of drug and gene delivery applications, due to their low cytotoxicity, controllable size, and unique architecture.\\u000a This review will summarize the potential applications of polyrotaxanes in the field of drug delivery and gene delivery. Generally,\\u000a cyclodextrin-based biodegradable polypseudorotaxane hydrogels could be

Jia Jing Li; Feng Zhao; Jun Li

199

Infrared free electron laser enhanced transdermal drug delivery  

NASA Astrophysics Data System (ADS)

It is necessary to control enhancement of transdermal drug delivery with non-invasive. The present study was investigated to assess the effectivity of enhancing the drug delivery by irradiating 6-?m region mid infrared free electron laser (MIR-FEL). The enhancement of transdermal drug (lidocaine) delivery of the samples (hairless mouse skin) irradiated with lasers was examined for flux (?g/cm2/h) and total penetration amount (?g/cm2) of lidocaine by High performance Liquid Chromatography (HPLC). The flux and total amount penatration date was enhanced 200-300 fold faster than the control date by the laser irradiation. FEL irradiating had the stratum corneum, and had the less thermal damage in epidermis. The effect of 6-?m region MIR-FEL has the enhancement of transdermal drug delivery without removing the stratum corneum because it has the less thermal damage. It leads to enhancement drug delivery system with non-invasive laser treatment.

Awazu, Kunio; Uchizono, Takeyuki; Suzuki, Sachiko; Yoshikawa, Kazushi

2005-08-01

200

UNC study shows potential to revive abandoned cancer drug by nanoparticle drug delivery  

Cancer.gov

Current nanomedicine research has focused on the delivery of established and novel therapeutics. But a UNC team is taking a different approach. They developed nanoparticle carriers to successfully deliver therapeutic doses of a cancer drug that had previously failed clinical development due to pharmacologic challenges. They report their proof of principle findings in the April 30, 2012 early online edition of Proceedings of the National Academy of Sciences.

201

[Research advances in brain-targeted nanoscale drug delivery system].  

PubMed

The blood-brain barrier (BBB) exerts its central nervous system (CNS) protective function as it hinders the delivery of diagnostic and therapeutic agents to the brain. With the development of nanotechnology during the last thirty years, the nanocarriers for delivering drugs make it possible to transport drugs across the BBB. The brain-targeted drug delivery system usually consists of two parts: nanocarriers and brain-targeted strategies. In this review, several kinds of nanocarriers are introduced for brain-targeted drug delivery. We focus on several possible strategies for brain-targeting and comment on their advantages and disadvantages in application. PMID:24417079

Liu, Yang; Jiang, Chen

2013-10-01

202

Microemulsion: New Insights into the Ocular Drug Delivery  

PubMed Central

Delivery of drugs into eyes using conventional drug delivery systems, such as solutions, is a considerable challenge to the treatment of ocular diseases. Drug loss from the ocular surface by lachrymal fluid secretion, lachrymal fluid-eye barriers, and blood-ocular barriers are main obstacles. A number of ophthalmic drug delivery carriers have been made to improve the bioavailability and to prolong the residence time of drugs applied topically onto the eye. The potential use of microemulsions as an ocular drug delivery carrier offers several favorable pharmaceutical and biopharmaceutical properties such as their excellent thermodynamic stability, phase transition to liquid-crystal state, very low surface tension, and small droplet size, which may result in improved ocular drug retention, extended duration of action, high ocular absorption, and permeation of loaded drugs. Further, both lipophilic and hydrophilic characteristics are present in microemulsions, so that the loaded drugs can diffuse passively as well get significantly partitioned in the variable lipophilic-hydrophilic corneal barrier. This review will provide an insight into previous studies on microemulsions for ocular delivery of drugs using various nonionic surfactants, cosurfactants, and associated irritation potential on the ocular surface. The reported in vivo experiments have shown a delayed effect of drug incorporated in microemulsion and an increase in the corneal permeation of the drug. PMID:23936681

Hegde, Rahul Rama; Verma, Anurag; Ghosh, Amitava

2013-01-01

203

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

204

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

205

A PZT insulin pump integrated with a silicon microneedle array for transdermal drug delivery  

Microsoft Academic Search

Many of the compounds in drugs cannot be effectively delivered using current drug delivery techniques (e.g., pills and injections). Transdermal delivery is an attractive alternative, but it is limited by the extremely low permeability of the skin. As the primary barrier to transport is located in the upper tissue, Micro-Electro-Mechanical-System (MEMS) technology provides novel means, such as microneedle array and

Bin Ma; Sheng Liu; Zhiyin Gan; Guojun Liu; Xinxia Cai; Honghai Zhang; Zhigang Yang

2006-01-01

206

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

207

BULK TITANIUM MICRONEEDLES WITH EMBEDDED MICROFLUIDIC NETWORKS FOR TRANSDERMAL DRUG DELIVERY  

E-print Network

BULK TITANIUM MICRONEEDLES WITH EMBEDDED MICROFLUIDIC NETWORKS FOR TRANSDERMAL DRUG DELIVERY E. R, robust platform for transdermal drug delivery applications. 1. INTRODUCTION Microfabrication techniques for low-cost transdermal drug delivery and diagnostic applications. Owing to its biocompatibility

MacDonald, Noel C.

208

Sustained Release Intraocular Drug Delivery Devices for Treatment of Uveitis  

PubMed Central

Corticosteroids have been the mainstay of uveitis therapy. When intraocular inflammation is unresponsive to steroids, or steroid related side effects become a concern, steroid-sparing medications may be administered which can be classified into immunosuppressive and immunomodulatory agents. Uveitis treatment can be delivered systemically, topically, periocularly or intraocularly. All of the above mentioned medications can entail significant systemic side effects, particularly if administered for prolonged durations, which may become treatment-limiting. Some medications, particularly hydrophobic compounds, may poorly cross the blood–retinal barrier. Topical medications, which have the least side effects, do not penetrate well into the posterior segment and are unsuitable for posterior uveitis which is often sight-threatening. Intraocular or periocular injections can deliver relatively high doses of drug to the eye with few or no systemic side effects. However, such injections are associated with significant complications and must often be repeated at regular intervals. Compliance with any form of regular medication can be a problem, particularly if its administration is associated with discomfort or if side effects are unpleasant. To overcome the above-mentioned limitations, an increasing number of sustained-release drug delivery devices using different mechanisms and containing a variety of agents have been developed to treat uveitis. This review discusses various current and future sustained-release ophthalmic drug delivery systems for treatment of uveitis. PMID:22454753

Haghjou, Nahid; Soheilian, Masoud; Abdekhodaie, Mohammad Jafar

2011-01-01

209

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

210

Novel nanocarriers for topical drug delivery: investigating delivery efficiency and distribution in skin using two-photon microscopy  

NASA Astrophysics Data System (ADS)

The complex structure of skin represents an effective barrier against external environmental factors, as for example, different chemical and biochemical compounds, yeast, bacterial and viral infections. However, this impermeability prevents efficient transdermal drug delivery which limits the number of drugs that are able to penetrate the skin efficiently. Current trends in drug application through skin focus on the design and use of nanocarriers for transport of active compounds. The transport systems applied so far have several drawbacks, as they often have low payload, high toxicity, a limited variability of inclusion molecules, or long degradation times. The aim of these current studies is to investigate novel topical drug delivery systems, e.g. nanocarriers based on cyclic oligosaccharides - cyclodextrins (CD) or iron (III)-based metal-organic frameworks (MOF). Earlier studies on cell cultures imply that these drug nanocarriers show promising characteristics compared to other drug delivery systems. In our studies, we use two-photon microscopy to investigate the ability of the nanocarriers to deliver compounds through ex-vivo skin samples. Using near infrared light for excitation in the so called optical window of skin allows deep-tissue visualization of drug distribution and localization. In addition, it is possible to employ two-photon based fluorescence correlation spectroscopy for quantitative analysis of drug distribution and concentrations in different cell layers.

Kirejev, Vladimir; Guldbrand, Stina; Bauer, Brigitte; Smedh, Maria; Ericson, Marica B.

2011-03-01

211

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

212

Recent trends in oral drug delivery: a review.  

PubMed

There are many ways to deliver drugs into the body, viz oral (through swallowing), sub mucosal (through buccal and sublingual mucosa), parenteral (through injection), transdermal (through skin), pulmonary (through inhalation) etc. Among these deliveries oral delivery (by swallowing) is widely accepted. In oral drug delivery, many scientific challenges and breakthrough technologies are required to generate novel dosage forms raising drug delivery to higher level. Some are self emulsifying systems, solid self nanoemulsion, polymeric micelles, spray freezing, pH controlled systems, time delayed system, osmotic pumps, prodrugs etc. This paper reviews recent patents, technologies and products with their importance, manufacturing and novel approaches implemented till date to overcome the challenges in oral drug delivery systems. PMID:19519576

Gupta, Himanshu; Bhandari, Dinesh; Sharma, Aarti

2009-06-01

213

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

214

Novel therapeutic modalities and drug delivery in pancreatic cancer - an ongoing search for improved efficacy.  

PubMed

Pancreatic cancer is an incredibly challenging disease due to its high rates of resistance to traditional chemotherapy and radiotherapy. There has been little improvement in the prognosis of pancreatic cancer cases in the past decades, highlighting the crucial need for more effective therapeutic approaches. Erlotinib, an EGFR inhibitor, and gemcitabine, a nucleoside analog, are currently used in combination for chemotherapy treatment, but new developments in drug delivery systems using liposomes and nanoparticles may be promising new modalities for management of the disease. In addition to standard chemotherapeutic drugs, these delivery systems can be utilized to deliver therapeutic agents such as siRNA, oncolytic viruses, small molecule inhibitors, antibodies, and suicide genes. Further work is required to elucidate how ligands and antibodies could be used to enhance the targeted delivery of drugs, thus increasing specificity, improving stability, and reducing the effect of the drugs on healthy tissue. Despite significant preclinical data, there are currently very few clinical trials involving pancreatic cancer targeted drug delivery. This article summarizes current developments in targeted pancreatic cancer drug delivery, focusing on delivery systems, targets, and therapeutic agents. PMID:24432033

Zhang, Yuqing; Satoh, Kei; Li, Min

2012-12-11

215

Trends in drug delivery through tissue barriers containing tight junctions.  

PubMed

A limitation in the uptake of many drugs is the restricted permeation through tissue barriers. There are two general ways to cross barriers formed by cell layers: by transcytosis or by diffusion through the intercellular space. In the latter, tight junctions (TJs) play the decisive role in the regulation of the barrier permeability. Thus, transient modulation of TJs is a potent strategy to improve drug delivery. There have been extensive studies on surfactant-like absorption enhancers. One of the most effective enhancers found is sodium caprate. However, this modulates TJs in an unspecific fashion. A novel approach would be the specific modulation of TJ-associated marvel proteins and claudins, which are the main structural components of the TJs. Recent studies have identified synthetic peptidomimetics and RNA interference techniques to downregulate the expression of targeted TJ proteins. This review summarizes current progress and discusses the impact on TJs' barrier function. PMID:24665392

Tscheik, Christian; Blasig, Ingolf E; Winkler, Lars

2013-04-01

216

Microneedle technologies for (trans)dermal drug and vaccine delivery.  

PubMed

Microneedles have been used for the dermal and transdermal delivery of a broad range of drugs, such as small molecular weight drugs, oligonucleotides, DNA, peptides, proteins and inactivated viruses. However, until now there are no microneedle-based (trans)dermal drug delivery systems on the market. In the past decade various types of microneedles have been developed by a number of production processes. Numerous geometries of microneedles have been designed from various materials. These microneedles have been used for different approaches of microneedle-based (trans)dermal drug delivery. Following a brief introduction about dermal and transdermal drug delivery, this review describes different production methods for solid and hollow microneedles as well as conditions that influence skin penetration. Besides, the four microneedle-based (trans)dermal drug delivery approaches are discussed: "poke and flow", "poke and patch", "poke and release", and "coat and poke". A separate section of this review is devoted to the use of microneedles for the delivery of therapeutic proteins and vaccines. Finally, we give our view on research and development that is needed to render microneedle-based (trans)dermal drug delivery technologies clinically useful in the near future. PMID:22342643

van der Maaden, Koen; Jiskoot, Wim; Bouwstra, Joke

2012-07-20

217

Colonic drug delivery systems based on natural polysaccharides and their evaluation.  

PubMed

Natural polysaccharides are found in abundance, are inexpensive, safe and available in a variety of structures which can easily be modified chemically and biochemically. A number of natural gums and mucilages along with their chemically modified forms have been evaluated as controlled drug delivery devices. They are reported to be capable of providing the desired drug release profiles and in some cases, have shown comparable drug release properties with currently available sustained release products in the market. Colon specific drug delivery based on natural polysaccharides has highly been acclaimed in recent years. A colon specific drug delivery system should prevent drug release in the stomach as well as the small intestine. Several polysaccharides have been reported to be capable of preventing drug release in the upper GI tract while being susceptible to enzymatic degradation by colonic bacterial enzymes. A wide range of natural or modified polysaccharides has been investigated for peroral delivery of drugs to the colon. As the release of drug from these polysaccharides based systems is independent of pH and gastric emptying time these polysaccharides based systems are considered the most effective and preferable means for colonic drug delivery in terms of target specificity. PMID:24032514

Pachuau, Lalduhsanga; Mazumder, Bhaskar

2013-11-01

218

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

219

Development of polymer-polysaccharide hydrogels for controlling drug delivery  

NASA Astrophysics Data System (ADS)

The use of polymers as biomaterials has evolved over the past several decades, encompassing an expanding synthetic toolbox and many bio-mimetic approaches. Both synthetic and natural polymers have been used as components for biomaterials as their unique chemical structures can provide specific functions for desired applications. Of these materials, heparin, a highly sulfated naturally occurring polysaccharide, has been investigated extensively as a core component in drug delivery platforms and tissue engineering. The goal of this work was to further explore the use of heparin via conjugation with synthetic polymers for applications in drug delivery. We begin by investigating low molecular weight heparin (LMWH), a depolymerized heparin that is used medicinally in the prevention of thrombosis by subcutaneous injection or intravenous drip. Certain disease states or disorders require frequent administration with invasive delivery modalities leading to compliance issues for individuals on prolonged therapeutic courses. To address these issues, a long-term delivery method was developed for LMWH via subcutaneous injection of in situ hydrogelators. This therapy was accomplished by chemical modification of LMWH with maleimide functionality so that it may be crosslinked into continuous hydrogel networks with four-arm thiolated polyethylene glycol (PEG-SH). These hydrogels degrade via hydrolysis over a period of weeks and release bioactive LMWH with first-order kinetics as determined by in vitro and in vivo models, thus indicating the possibility of an alternative means of heparin delivery over current accepted methodologies. Evaluation of the maleimide-thiol chemistries applied in the LMWH hydrogels revealed reversibility for some conjugates under reducing conditions. Addition chemistries, such as maleimide-thiol reactions, are widely employed in biological conjugates and are generally accepted as stable. Here we show that the resulting succinimide thioether formed by the Michael type addition of thiol derivatives to N-ethylmaleimide (NEM) undergoes retro and exchange reactions in the presence of other thiol compounds at physiological pH and temperature. Model studies of NEM conjugated to various thiols (4-mercaptophenylacetic acid (MPA), N-acetylcysteine, or 3-mercaptopropionic acid (MP)), incubated with a naturally occurring reducing agent, glutathione, showed half-lives from 20-80 hrs with extents of conversion from 20-90% for MPA and N-acetylcysteine conjugates. The kinetics of the retro reactions and extent of exchange can be modulated by the Michael donor's reactivity; therefore the degradation of maleimide-thiol adducts could be tuned for controlled release of drugs or degradation of materials at timescales different than those currently possible via disulfide-mediated release. The reduction sensitive maleimide-thiol chemistry was then investigated as a crosslinking mechanism for LMWH hydrogels. Crosslinking maleimide functionalized LMWH with PEG functionalized with thiophenyl functionalities imparted glutathione sensitivity. 4-mercaptophenylpropionic acid and 2,2-dimethyl-3-(4-mercaptophenyl)propionic acid, induced sensitivity to glutathione as shown by a decrease in degradation time of 4x and 5x respectively. The pseudo-first order retro reaction constants were approximately an order of magnitude slower than hydrogels crosslinked via disulfide linkages, indicating the potential use of the retro succinimide-thioether covalent bonds for reduction mediated release and/or degradation with increased blood stability and prolonged drug delivery timescales compared to disulfide chemistries. In summary, this work highlights the use of polymer-polysaccharide hydrogels composed of LMWH and PEG as investigated for drug delivery and as a tool for elucidating a novel reduction sensitive controlled release mechanism.

Baldwin, Aaron David

220

Tumor-targeting drug delivery of new-generation taxoids  

PubMed Central

A long-standing problem of conventional cancer chemotherapy is the lack of tumor specificity. Tumor-targeting drug-delivery systems have been explored to overcome this problem. These systems combine a powerful cytotoxic anticancer agent with a tumor-targeting molecule via a ‘smart’ linker to form highly efficacious drug conjugates. These drug conjugates can deliver potent cytotoxic drugs specifically to tumors and tumor cells with minimal systemic toxicity. This review describes our groups’ research on the molecular approaches to the design and development of a novel drug-delivery system bearing highly potent new-generation taxoids for tumor-targeting chemotherapy in our laboratory. PMID:22168163

Ojima, Iwao; Zuniga, Edison S; Berger, William T; Seitz, Joshua D

2012-01-01

221

Tumor-targeting drug delivery of new-generation taxoids.  

PubMed

A long-standing problem of conventional cancer chemotherapy is the lack of tumor specificity. Tumor-targeting drug-delivery systems have been explored to overcome this problem. These systems combine a powerful cytotoxic anticancer agent with a tumor-targeting molecule via a 'smart' linker to form highly efficacious drug conjugates. These drug conjugates can deliver potent cytotoxic drugs specifically to tumors and tumor cells with minimal systemic toxicity. This review describes our groups' research on the molecular approaches to the design and development of a novel drug-delivery system bearing highly potent new-generation taxoids for tumor-targeting chemotherapy in our laboratory. PMID:22168163

Ojima, Iwao; Zuniga, Edison S; Berger, William T; Seitz, Joshua D

2012-01-01

222

Gaining the Upper Hand on Pulmonary Drug Delivery  

PubMed Central

Asthma, Chronic Obstructive Pulmonary Disease (COPD) and Cystic Fibrosis (CF) are all pulmonary diseases which are characterized by chronic inflammation and an increase in mucus production. Excess mucus in the airways correlates with pathophysiology such as a decline in lung function and prolonged bacterial infections. New drugs to treat these chronic respiratory diseases are currently being developed and include both inhaled and orally administered compounds. Whilst oral drugs may be easier to administer, they are more prone to side-effects due to higher bioavailability. Inhaled compounds may show reduced bioavailability, but face their own unique challenges. For example, thick mucus in the respiratory tracts of asthma, CF and COPD patients can act as a physical barrier that impedes drug delivery. Mucus also contains a high number of enzymes and proteases that may degrade compounds before they reach their site of action. Furthermore, some classes of drugs are rapidly absorbed across the respiratory epithelia into systemic circulation, which may limit their duration of action and/or cause off-target effects. This review discusses some of the different treatment options that are currently available and the considerations that need to be taken into account to produce new therapies for the treatment of chronic respiratory diseases. PMID:25126589

Tyrrell, Jean; Tarran, Robert

2014-01-01

223

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

224

Role of monocarboxylate transporters in drug delivery to the brain.  

PubMed

Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate and butyrate. Currently, fourteen members of this transporter family have been identified by sequence homology, of which only the first four members (MCT1- MCT4) have been shown to mediate the proton-linked transport of monocarboxylates. Another transporter family involved in the transport of endogenous monocarboxylates is the sodium coupled MCTs (SMCTs). These act as a symporter and are dependent on a sodium gradient for their functional activity. MCT1 is the predominant transporter among the MCT isoforms and is present in almost all tissues including kidney, intestine, liver, heart, skeletal muscle and brain. The various isoforms differ in terms of their substrate specificity and tissue localization. Due to the expression of these transporters in the kidney, intestine, and brain, they may play an important role in influencing drug disposition. Apart from endogenous short chain monocarboxylates, they also mediate the transport of exogenous drugs such as salicylic acid, valproic acid, and simvastatin acid. The influence of MCTs on drug pharmacokinetics has been extensively studied for ?-hydroxybutyrate (GHB) including distribution of this drug of abuse into the brain and the results will be summarized in this review. The physiological role of these transporters in the brain and their specific cellular localization within the brain will also be discussed. This review will also focus on utilization of MCTs as potential targets for drug delivery into the brain including their role in the treatment of malignant brain tumors. PMID:23789956

Vijay, Nisha; Morris, Marilyn E

2014-01-01

225

Understanding and Predicting Drug Delivery from Hydrophilic Matrix  

E-print Network

and diclofenac sodium was studied in phosphate buffer (pH 7.4) and 0.1 M HCl, respectively. The initial drugUnderstanding and Predicting Drug Delivery from Hydrophilic Matrix Tablets Using the "Sequential phenomena which are involved in the swelling and drug release from hydrophilic matrix tablets using

Peppas, Nicholas A.

226

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:1681­1702, 2008 Keywords: biodegradable polymers; imaging methods; cancer chemotherapy; drug transport; controlled release; mathematical model; drug targeting INTRODUCTION Cancer is an enormous health concern

Gao, Jinming

227

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

228

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

229

Dendrimeric systems and their applications in ocular drug delivery.  

PubMed

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; Pehlivan, Sibel Bozda?; Unlü, Nur?en

2013-01-01

230

Recent patents survey on self emulsifying drug delivery system.  

PubMed

Self-Emulsifying Drug Delivery System is a unique feasible approach to overcome low oral bioavailability problem which is associated with the hydrophobic drugs due to their unparalleled potential as a drug delivery with the broad range of application. The estimated 40% of active pharmaceuticals are poorly water soluble. Now recently, formulation containing oral SEDDS has received much interest as it solve problems related to oral bioavailability, intra and inter-subject variability and lack of dose proportionality of hydrophobic drugs. Now a days, it is the first way to investigate the development of any kind of innovative dosage forms. Many important in-vitro characteristics such as surfactant concentration, oil/surfactant ratio, emulsion polarity, droplet size and zeta potential play an important role in oral absorption of drug from SEEDS. It can be orally administered in the form of SGC or HGC and also enhances bioavailability of drugs to increase solubility and minimizes the gastric irritation. After administration the drug remains entrapped in the oily droplets (inside the droplet or in the surfactant`s film at the interface) of the emulsion that are formed in the GIT upon self-emulsification process. It is also a bit problematic to say that the drug is being released from SMEDDS, it would be more precise to say that it diffuses out of oily droplets into the GIT media resulting in the formation of an equilibrium between the drug dissolved in oily droplets and the outer dispersed media (e.g. GIT fluids). Many of the application and preparation methods of SEDDS are reported by research articles and patents in different countries. We present an exhaustive and updated account of numerous literature reports and more than 150 patents published on SEDDS in the recent period. This current patent review is useful in knowledge of SEDDS for its preparations and patents in different countries with emphasis on their formulation, characterization and systematic optimization strategies, thus paving the way for accelerated progress into the SEDDS application in pharmaceutical research as well as patents on SEDDS methods. PMID:25146965

Jethara, Sahilhusen I; Patel, Alpesh D; Patel, Mukesh R

2014-01-01

231

Nanoparticles as Drug Delivery Systems in Cancer Medicine: Emphasis on RNAi-Containing Nanoliposomes  

PubMed Central

Nanomedicine is a growing research field dealing with the creation and manipulation of materials at a nanometer scale for the better treatment, diagnosis and imaging of diseases. In cancer medicine, the use of nanoparticles as drug delivery systems has advanced the bioavailability, in vivo stability, intestinal absorption, solubility, sustained and targeted delivery, and therapeutic effectiveness of several anticancer agents. The expansion of novel nanoparticles for drug delivery is an exciting and challenging research filed, in particular for the delivery of emerging cancer therapies, including small interference RNA (siRNA) and microRNA (miRNAs)-based molecules. In this review, we focus on the currently available drug delivery systems for anticancer agents. In addition, we will discuss the promising use of nanoparticles for novel cancer treatment strategies. PMID:24287462

Rivera Diaz, Monica; Vivas-Mejia, Pablo E.

2013-01-01

232

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

233

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

234

Recent advances in gastric floating drug delivery technology: a review.  

PubMed

Gastric floating drug delivery systems have been an avenue of considerable interest in terms of their immense potential for better pharmacotherapeutic interventions along with site-specific absorption. These buoyant systems significantly enhance the bioavailability and controlled delivery of several drug molecules. Scientific investigators have also carried out substantial research endeavours worldwide in order to design a more systematic and intellectual floating systems. The present manuscript is an attempt to highlight numerous recent advancements in the design of gastric floating drug delivery systems along with various available commercial preparations. Salient applications, characterization aspects and future perspectives of these multifarious systems have also been addressed. PMID:23808593

Pahwa, Rakesh; Bisht, Seema; Kumar, Vipin; Kohli, Kanchan

2013-06-01

235

Supramolecular polymers based on cyclodextrins for drug and gene delivery.  

PubMed

Supramolecular polymers based on cyclodextrins (CDs) have inspired interesting and rapid developments as novel biomaterials in a broad range of drug and gene delivery applications, due to their low cytotoxicity, controllable size, and unique architecture. This review will summarize the potential applications of polyrotaxanes in the field of drug delivery and gene delivery. Generally, cyclodextrin-based biodegradable polypseudorotaxane hydrogels could be used as a promising injectable drug delivery system for sustained and controlled drug release. Temperature-responsive, pH-sensitive, and controllable hydrolyzable polyrotaxane hydrogels have attracted much attention because of their controllable properties, and the self-assembly micelles formed by amphiphilic copolymer threaded with CDs could be used as a carrier for controlled and sustained drug release. Polyrotaxanes with drug or ligand conjugated CDs threaded on a polymer chain with a biodegradable end group could be useful for controlled and multivalent targeted delivery. In the field of gene delivery, cationic polyrotaxanes consisting of multiple OEI-grafted CDs threaded on a block copolymer chain are attractive non-viral gene carries due to the strong DNA-binding ability, low cytotoxicity, and high gene delivery capability. Furthermore, cytocleavable end-caps were introduced in the polyrotaxane systems in order to ensure efficient endosomal escape for intracellular trafficking of DNA. The development of the supramolecular approach using CD-containing polyrotaxanes is expected to provide a new paradigm for biomaterials. PMID:20839082

Li, Jia Jing; Zhao, Feng; Li, Jun

2011-01-01

236

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.

237

Mesoporous Silica Nanoparticles as Controlled Release Drug Delivery and Gene Transfection Carriers  

SciTech Connect

In this review, we highlight the recent research developments of a series of surface-functionalized mesoporous silica nanoparticle (MSN) materials as efficient drug delivery carriers. The synthesis of this type of MSN materials is described along with the current methods for controlling the structural properties and chemical functionalization for biotechnological and biomedical applications. We summarized the advantages of using MSN for several drug delivery applications. The recent investigations of the biocompatibility of MSN in vitro are discussed. We also describe the exciting progress on using MSN to penetrate various cell membranes in animal and plant cells. The novel concept of gatekeeping is introduced and applied to the design of a variety of stimuli-responsive nanodevices. We envision that these MSN-based systems have a great potential for a variety of drug delivery applications, such as the site-specific delivery and intracellular controlled release of drugs, genes, and other therapeutic agents.

Igor I. Slowing; Juan L. Viveo-Escoto; Chia-Wen Wu; Victor S. Y. Lin

2008-04-10

238

Recent Applications of Mesoscale Modeling to Nanotechnology and Drug Delivery.  

National Technical Information Service (NTIS)

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 ...

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

2005-01-01

239

Needle-free drug delivery using shock wave techniques  

E-print Network

A recent advancement in the area of needle-free injection systems has been the development of devices capable of epidermal delivery of powder medications. These devices use high-pressure compressed gas to accelerate drug ...

Pavlov, Atanas (Atanas Ivanov)

2006-01-01

240

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

241

Coacervate delivery systems for proteins and small molecule drugs.  

PubMed

Coacervates represent an exciting new class of drug delivery vehicles, developed in the past decade as carriers of small molecule drugs and proteins. This review summarizes several well-described coacervate systems, including: i) elastin-like peptides for delivery of anticancer therapeutics; ii) heparin-based coacervates with synthetic polycations for controlled growth factor delivery; iii) carboxymethyl chitosan aggregates for oral drug delivery; iv) Mussel adhesive protein and hyaluronic acid coacervates. Coacervates present advantages in their simple assembly and easy incorporation into tissue engineering scaffolds or as adjuncts to cell therapies. They are also amenable to functionalization such as for targeting or for enhancing the bioactivity of their cargo. These new drug carriers are anticipated to have broad applications and noteworthy impact in the near future. PMID:25138695

Johnson, Noah R; Wang, Yadong

2014-12-01

242

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

243

Microneedles for Drug Delivery via the Gastrointestinal Tract  

E-print Network

Both patients and physicians prefer the oral route of drug delivery. The gastrointestinal (GI) tract, though, limits the bioavailability of certain therapeutics because of its protease and bacteria-rich environment as well ...

Schroeder, Avi

244

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

245

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

246

Microneedle-based drug delivery systems: microfabrication, drug delivery, and safety.  

PubMed

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

2010-05-01

247

A water-powered micro drug delivery system  

Microsoft Academic Search

A plastic micro drug delivery system has been successfully demonstrated by utilizing the principle of osmosis without any electrical power consumption. The system has an osmotic microactuator (see Su, Lin, and Pisano, J. Microelectromech., vol. 11, pp. 736-7462, Dec. 2002) and a polydimethylsiloxane (PDMS) microfluidic cover compartment consisting of a reservoir, a microfluidic channel and a delivery port. The typical

Yu-Chuan Su; Liwei Lin

2004-01-01

248

Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation  

PubMed Central

Transdermal administration of drugs is generally limited by the barrier function of the skin. Vesicular systems are one of the most controversial methods for transdermal delivery of active substances. The interest in designing transdermal delivery systems was relaunched after the discovery of elastic vesicles like transferosomes, ethosomes, cubosomes, phytosomes, etc. This paper presents the composition, mechanisms of penetration, manufacturing and characterization methods of transferosomes as transdermal delivery systems of active substances. For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport. For the drugs to be delivered to the body, they should cross the membranous barrier. The concept of these delivery systems was designed in an attempt to concentrate the drug in the tissues of interest, while reducing the amount of drug in the remaining tissues. Hence, surrounding tissues are not affected by the drug. In addition, loss of drug does not happen due to localization of drug, leading to get maximum efficacy of the medication. Therefore, the phospholipid based carrier systems are of considerable interest in this era. PMID:22171309

Rajan, Reshmy; Jose, Shoma; Mukund, V. P. Biju; Vasudevan, Deepa T.

2011-01-01

249

Targeting homeostasis in drug delivery using bioresponsive hydrogel microforms.  

PubMed

A drug delivery platform comprising a biocompatible, bioresponsive hydrogel and possessing a covalently tethered peptide-drug conjugate was engineered to achieve stasis, via a closed control loop, of the external biochemical activity of the actuating protease. The delivery platform contains a peptide-drug conjugate covalently tethered to the hydrogel matrix, which in the presence of the appropriate protease, was cleaved and the drug released into the bathing environment. This platform was developed and investigated in silico using a finite element modeling (FEM) approach. Firstly, the primary governing phenomena guiding drug release profiles were investigated, and it was confirmed that under transport-limited conditions, the diffusion of the enzyme within the hydrogel and the coupled enzyme kinetics accurately model the system and are in agreement with published results. Secondly, the FEM model was used to investigate the release of a competitive protease inhibitor, MAG283, via cleavage of Acetyl-Pro-Leu-Gly|Leu-MAG-283 by MMP9 in order to achieve targeted homeostasis of MMP-9 activity, such as in the pathophysiology of chronic wounds, via closed-loop feedback control. The key engineering parameters for the delivery device are the radii of the hydrogel microspheres and the concentration of the peptide-inhibitor conjugate. Homeostatic drug delivery, where the focus turns away from the drug release rate and turns toward achieving targeted control of biochemical activity within a biochemical pathway, is an emerging approach in drug delivery methodologies for which the potential has not yet been fully realized. PMID:24333901

Wilson, A Nolan; Guiseppi-Elie, Anthony

2014-01-30

250

Electrically-Assisted Transdermal Drug Delivery  

Microsoft Academic Search

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

Jim E. Riviere; Mark C. Heit

1997-01-01

251

Intrinsically Conducting Polymer Platforms for Electrochemically Controlled Drug Delivery  

Microsoft Academic Search

\\u000a Intrinsically conducting polymers (ICPs) combine the physical properties of polymers with the electrical properties of metals.\\u000a This unique group of polymers can be loaded with drugs and then electrochemically stimulated to control the rate at which\\u000a drug is released. Drug delivery systems based on ICPs have the exciting potential to match treatment requirements with highly\\u000a controlled drug release using facile

Darren Svirskis; Bryon E. Wright; Jadranka Travas-Sejdic; Sanjay Garg

252

NMR characterisation and transdermal drug delivery potential of microemulsion systems  

Microsoft Academic Search

The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol\\/Plurol Isostearique\\/isostearylic isostearate\\/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride), and to compare the drug delivery potential of microemulsions to conventional vehicles. Self-diffusion coefficients determined by pulsed-gradient spin-echo NMR spectroscopy and T1 relaxation times were

Mads Kreilgaard; Erik J Pedersen; Jerzy W Jaroszewski

2000-01-01

253

Macro and Microstructure of the Airways for Drug Delivery  

Microsoft Academic Search

\\u000a Both anatomy and physiology of the airways are critical for understanding and predicting the dynamics of drug delivery systems\\u000a that are inhaled. This theme that intimately links the biology of the airways to the response of pulmonary drug delivery systems\\u000a is present throughout other following chapters in this book. Therefore, it is ideal to introduce these concepts in this chapter

Kevin P. O’Donnell; Hugh D. C. Smyth

254

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

255

Targeting blood-brain barrier changes during inflammatory pain: an opportunity for optimizing CNS drug delivery  

PubMed Central

The blood–brain barrier (BBB) is the most significant obstacle to effective CNS drug delivery. It possesses structural and biochemical features (i.e., tight-junction protein complexes and, influx and efflux transporters) that restrict xenobiotic permeation. Pathophysiological stressors (i.e., peripheral inflammatory pain) can alter BBB tight junctions and transporters, which leads to drug-permeation changes. This is especially critical for opioids, which require precise CNS concentrations to be safe and effective analgesics. Recent studies have identified molecular targets (i.e., endogenous transporters and intracellular signaling systems) that can be exploited for optimization of CNS drug delivery. This article summarizes current knowledge in this area and emphasizes those targets that present the greatest opportunity for controlling drug permeation and/or drug transport across the BBB in an effort to achieve optimal CNS opioid delivery. PMID:22468221

Ronaldson, Patrick T; Davis, Thomas P

2012-01-01

256

Novel prospective in colon specific drug delivery system.  

PubMed

This review deals with the targeting of drugs to the lower gastrointestinal tract i.e. colon. Colonic drug delivery becomes important for localized action as well as for improved systemic availability of peptide and proteins. Drugs which have absorption window in the colonic region have been targeted using different novel technologies. pH sensitive polymers and prodrug based formulation have been used for the delivery of drugs into the colon. Different natural polymers have been used successfully for the delivery of drugs into the colon. Natural polymers are less toxic, biodegradable and easily available with a wide range of molecular weight and varying chemical compositions. One of the supporting properties associated with these polymers is that natural polymers can be used as approved pharmaceutical excipient. PMID:24967782

Bansal, Vipin; Malviya, Rishabha; Malaviya, Tanya; Sharma, Pramod Kumar

2014-01-01

257

Role of efflux pumps and metabolising enzymes in drug delivery.  

PubMed

The impact of efflux pumps and metabolic enzymes on the therapeutic activity of various drugs has been well established. The presence of efflux pumps on various tissues and tumours has been shown to regulate the intracellular concentration needed to achieve therapeutic activity. The notable members of efflux proteins include P-glycoprotein, multi-drug resistance protein and breast cancer resistance protein. These efflux pumps play a pivotal role not only in extruding xenobiotics but also in maintaining the body's homeostasis by their ubiquitous presence and ability to coordinate among themselves. In this review, the role of efflux pumps in drug delivery and the importance of their tissue distribution is discussed in detail. To improve pharmacokinetic parameters of substrates, various strategies that modulate the activity of efflux proteins are also described. Drug metabolising enzymes mainly include the cytochrome P450 family of enzymes. Extensive drug metabolism due to the this family of enzymes is the leading cause of therapeutic inactivity. Therefore, the role of metabolising enzymes in drug delivery and disposition is extensively discussed in this review. The synergistic relationship between metabolising enzymes and efflux proteins is also described in detail. In summary, this review emphasises the urgent need to make changes in drug discovery and drug delivery as efflux pumps and metabolising enzymes play an important role in drug delivery and disposition. PMID:16296794

Katragadda, Suresh; Budda, Balasubrahmanyam; Anand, Banmeet S; Mitra, Ashim K

2005-07-01

258

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

259

Solid lipid excipients - matrix agents for sustained drug delivery.  

PubMed

Lipid excipients are attracting interest from drug developers due to their performance, ease of use, versatility and their potential to generate intellectual property through innovation in drug delivery particularly in the case of modifying drug release systems. Many articles have described the use of lipid excipients to develop matrix modified release dosage forms in a range of processing techniques, therefore a comprehensive review is timely to collect together and analyze key information. This review article focuses on the utility of lipid excipients in solid sustained drug delivery systems with emphasis on the efficiency and robustness of these systems with respect to: (i) the choice of the manufacturing process and impact on drug release, (ii) the fundamental drug release mechanisms, (iii) resistance of the drug formulation under physiological conditions and (iv) long-term stability. Understanding the functionality of these versatile excipients in formulation is elementary for the development of highly robust lipid-based sustained release medicines. PMID:24929038

Rosiaux, Yvonne; Jannin, Vincent; Hughes, Sophie; Marchaud, Delphine

2014-08-28

260

Design of an Implantable Device for Ocular Drug Delivery  

PubMed Central

Ocular diseases, such as, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa require drug management in order to prevent blindness and affecting million of adults in USA and worldwide. There is an increasing need to develop devices for drug delivery to address ocular diseases. This study focuses on the design, simulation, and development of an implantable ocular drug delivery device consisting of micro-/nanochannels embedded between top and bottom covers with a drug reservoir made from polydimethylsiloxane (PDMS) which is silicon-based organic and biodegradable polymer. Several simulations were carried out with six different micro-channel configurations in order to see the feasibility for ocular drug delivery applications. Based on the results obtained, channel design of osmotic I and osmotic II satisfied the diffusion rates required for ocular drug delivery. Finally, a prototype illustrating the three components of the drug delivery design is presented. In the future, the device will be tested for its functionality and diffusion characteristics. PMID:22919500

Lee, Jae-Hwan; Pidaparti, Ramana M.; Atkinson, Gary M.; Moorthy, Ramana S.

2012-01-01

261

Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier  

PubMed Central

Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods. PMID:25136634

Upadhyay, Ravi Kant

2014-01-01

262

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

263

Transdermal Drug Delivery: Penetration Enhancement Techniques  

Microsoft Academic Search

There is considerable interest in the skin as a site of drug application both for local and systemic effect. However, the skin, in particular the stratum corneum, poses a formidable barrier to drug penetration thereby limiting topical and transdermal bioavailability. Skin penetration enhancement techniques have been developed to improve bioavailability and increase the range of drugs for which topical and

Heather A. E. Benson

2005-01-01

264

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

265

Targeting delivery of drugs in the vascular system  

PubMed Central

Delivery and effects of therapeutics remain suboptimal. Most drugs do not have affinity to their targets. Biotherapeutics including enzymes and genetic materials require specific sub-cellular addressing not attainable naturally. Endothelium, lining the luminal surface of blood vessels, represents a key therapeutic target in many diseases. Studies in cell culture and animal models revealed that targeted delivery of therapeutics to, into and across endothelium can be achieved using carriers targeted to specific molecules expressed on the surface of the endothelial cells. For example, cell adhesion molecules represent attractive targets for drug delivery. Rational design of the drug delivery systems (e.g., selection of optimal geometry and affinity to specific epitopes) provides an unprecedented level of control of such parameters of drug delivery as pharmacokinetics, circulation in blood, binding to selected endothelial cell phenotypes, anchoring on cell surface or internalization into the endothelium, subsequent intracellular addressing and duration of the effects. We discusse here key aspects of design of endothelium-targeted drug delivery systems with potential for translation into the clinical domain.

Muzykantov, Vladimir; Muro, Silvia

2014-01-01

266

Microsecond thermal ablation of skin for transdermal drug delivery Jeong Woo Lee a  

E-print Network

Microsecond thermal ablation of skin for transdermal drug delivery Jeong Woo Lee a , Priya Gadiraju ablation Transdermal drug delivery Thermal ablation is a promising mechanism to increase permeability for transdermal drug delivery. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Transdermal drug delivery

267

MICRO-ABLATION OF SKIN BY ARC-DISCHARGE JET EJECTION FOR TRANSDERMAL DRUG DELIVERY  

E-print Network

MICRO-ABLATION OF SKIN BY ARC-DISCHARGE JET EJECTION FOR TRANSDERMAL DRUG DELIVERY Priya D is a significant advance for transdermal drug delivery. Keywords: Transdermal drug delivery, Arc-discharge, jet ejection, Micro-ablation 1. INTRODUCTION Transdermal drug delivery [1] has gained importance recently

268

Clinical impact of serum proteins on drug delivery.  

PubMed

Among serum proteins albumin and transferrin have attracted the most interest as drug carriers in the past two decades. Prior to that, their potential use was overshadowed by the advent of monoclonal antibodies that was initiated by Milstein and Koehler in 1975. Meanwhile intensive pursuit of exploiting transferrin, but above all albumin as an exogenous or endogenous carrier protein for treating various diseases, primarily cancer, rheumatoid arthritis, diabetes and hepatitis has resulted in several marketed products and numerous clinical trials. While the use of transferrin has clinically been primarily restricted to immunotoxins, albumin-based drug delivery systems ranging from albumin drug nanoparticles, albumin fusion protein, prodrugs and peptide derivatives that bind covalently to albumin as well as physically binding antibody fragments and therapeutically active peptides are in advanced clinical trials or approved products. For treating diabetes, Levemir and Victoza that are myristic acid derivatives of human insulin or glucagon-like peptide 1 (GLP-1) act as long-acting peptides by binding to the fatty acid binding sites on circulating albumin to control glucose levels. Levemir from Novo Nordisk has already developed into a blockbuster since its market approval in 2004. Abraxane, an albumin paclitaxel nanoparticle as a water-soluble galenic formulation avoiding the use of cremophor/ethanol, transports paclitaxel through passive targeting as an albumin paclitaxel complex to the tumor site and is superior to conventional Taxol against metastatic breast cancer. INNO-206, an albumin-binding doxorubicin prodrug that also accumulates in solid tumors due to the enhanced permeability and retention (EPR) effect but releases the parent drug through acid cleavage, either intra- or extracellularly, is entering phase II studies against sarcoma. An expanding field is the use of albumin-binding antibody moieties which do not contain the fragment crystallizable (Fc) portion of, conventional immunoglobulin G (IgG) but are comprised of monovalent or bivalent light and/or heavy chains and incorporate an additional albumin-binding peptide or antibody domain. The most advanced antibody of this kind is ATN-103 (Ozoralizumab), a trivalent albumin-binding nanobody that neutralizes the pro-inflammatory tumor necrosis factor alpha (TNF-?) as a causative agent for exacerbating rheumatoid arthritis. ATN-103 is currently in multi-center phase II trials against this debilitating disease. In summary, because albumin as the most abundant circulating protein cannot only be used to improve the pharmacokinetic profile of therapeutically relevant peptides and the targeting moiety of antibodies but also for peptide-based targeting as well as low-molecular weight drugs to inflamed or malignant tissue, it is anticipated that R&D efforts of academia and the pharmaceutical industry in this field of drug delivery will prosper. PMID:22155554

Kratz, Felix; Elsadek, Bakheet

2012-07-20

269

Enzyme-digestible hydrogels for oral drug delivery  

Microsoft Academic Search

The application of controlled release technology to oral drug delivery has had minimal success due to (1) the relatively short and variable gastrointestinal (GI) residence time and (2) the variability in the type and quantity of lumenal contents which can influence drug release rates. Enzyme-digestible hydrogels were synthesized as a gastric retention device to control gastric emptying for long-term oral

Waleed Shalaby-Wahba Shalaby

1992-01-01

270

EK 131 BD p.1 Engineered Drug Delivery  

E-print Network

: physiological, economic, patient compliance, safety and/or ethical. Course Goal The goal of the course is to use the science, technology and contemporary issues surrounding the delivery of drugs Use a system dynamics://www.iseesystems.com/community/downloads/NetsimModels.aspx) Pharmacokinetics Play the role of physician, trying to keep the drug level in a virtual patient's bloodstream

271

Cooperative Nanoparticles for Tumor Detection and Photothermally Triggered Drug Delivery  

E-print Network

Cooperative Nanoparticles for Tumor Detection and Photothermally Triggered Drug Delivery By Ji and vessel permeability.[7,8] Hyperthermia can also enhance drug toxicity in cancer cells that are otherwise­21] In this Communication, we hypothesized that GNRs could be used to detect a diseased site and act as tumor

Bhatia, Sangeeta

272

Principles of Local Drug Delivery to the Inner Ear  

Microsoft Academic Search

As more and more substances have been shown in preclinical studies to be capable of preventing damage to the inner ear from exposure to noise, ototoxic drugs, ischemia, infection, inflammation, mechanical trauma and other insults, it is becoming very important to develop feasible and safe methods for the targeted delivery of drugs to specific regions in the inner ear. Recently

Alec N. Salt; Stefan K. Plontke

2009-01-01

273

Is transdermal drug delivery research still important today?  

Microsoft Academic Search

When measured by the number of medicines consumed or prescriptions written, the topical and transdermal routes of drug delivery pale into insignificance compared with oral therapy. Industrial colleagues, therefore, occasionally adopt a somewhat utilitarian stance and question the value of academic research into skin treatment and drug permeation, with the rather parochial argument that it is of limited use to

Brian W Barry

2001-01-01

274

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

275

Acute Myeloid Leukemia: Nanomedicine drug delivery system could improve chemotherapy  

E-print Network

by their cardiotoxicity and the development of drug-resistance of tumors. In addition, the efficiency of anthracyclines the pharmacological properties of anthracyclines, a novel nanomedicine drug delivery system has been developed reputation for innovative research, interdisciplinarity and successful training. Its 4 faculties (Engineering

Pfeifer, Holger

276

Processing of polymer nanofibers through electrospinning as drug delivery systems  

Microsoft Academic Search

The use of electrospun fibers as drug carriers could be promising in the future for biomedical applications, especially postoperative local chemotherapy. In this research work, electrospun fibers were developed as a new system for the delivery of ketoprofen as non-steroidal anti-inflammatory drug (NSAID). The fibers were made either from polycaprolactone (PCL) as a biodegradable polymer or polyurethane (PU) as a

El-Refaie Kenawy; Fouad I. Abdel-Hay; Mohamed H. El-Newehy; Gary E. Wnek

2009-01-01

277

A PARYLENE BELLOWS ELECTROCHEMICAL ACTUATOR FOR INTRAOCULAR DRUG DELIVERY  

E-print Network

was performed. We achieved an efficiency approaching 80% and over 1.5 mm deflection with our actuator. Wireless operation was also demonstrated. KEYWORDS Drug Delivery Device, Electrolysis Pump, Bellows, Intraocular reaction and drug with (2) a robust, high deflection Parylene bellows to prevent unwanted pH changes

Meng, Ellis

278

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

279

Drug delivery by polymeric nanoparticles induces autophagy in macrophages.  

PubMed

Drug delivery nanosystems are currently used in human therapy. In preliminary studies we have observed that Eudragit RS nanoparticles, prepared by nanoprecipitation or double emulsion techniques, are cytotoxic for NR8383 rat macrophages. In this study, we expand our previous analysis and suggest that unloaded Eudragit RS nanoparticles prepared by nanoprecipitation (NP/ERS) may induce important morphological and biochemical cellular modifications leading to cellular death. In NR8383 rat macrophages cell line exposed to doses varying from 15 to 100 ?g/mL, NP/ERS nanoparticles are internalized inside the cells, reach the mitochondria and alter the structure of these organelles. In addition, the exposure to nanoparticles induces cellular autophagy as demonstrated by electron microscopy analysis, microchip array, qRT-PCR and Western blot assays. Although toxicity of nanoparticles has already been evidenced, it is the first time that results show clearly that the toxicity of polymeric nanovectors may be related to an activation of autophagy. PMID:22119964

Eidi, H; Joubert, O; Némos, C; Grandemange, S; Mograbi, B; Foliguet, B; Tournebize, J; Maincent, P; Le Faou, A; Aboukhamis, I; Rihn, B H

2012-01-17

280

Strategies for Enhanced Drug Delivery to the Central Nervous System  

PubMed Central

Treating central nervous system diseases is very challenging because of the presence of a variety of formidable obstacles that impede drug delivery. Physiological barriers like the blood-brain barrier and blood-cerebrospinal fluid barrier as well as various efflux transporter proteins make the entry of drugs into the central nervous system very difficult. The present review provides a brief account of the blood brain barrier, the P-glycoprotein efflux and various strategies for enhancing drug delivery to the central nervous system. PMID:20046703

Dwibhashyam, V. S. N. M.; Nagappa, A. N.

2008-01-01

281

Chronopharmaceutics based modern colon specific drug delivery systems.  

PubMed

Colon-targeted delivery of bioactives has recently gained importance in addressing specific needs in the therapy of colon based diseases. Many approaches have been attempted for the development of colon-specific delivery systems, with not much success in the past. With the advancement in the field of chronobiology, modern drug delivery approaches have elevated to a new concept of chronopharmacology i.e. the ability to deliver the therapeutic agent to a patient in a staggered profile. The increasing research interest surrounding this delivery system has widened the areas of pharmaceutics in particular with many more sub-disciplines expected to coexist in the near future. Chronopharmaceutics based technology has eliminated the drawbacks associated with the conventional colon specific delivery systems. This review on chronopharmaceutics based delivery lays emphasis on the existing technologies and future development. PMID:22564168

Tiwari, Akanksha; Shukla, Raj Kumar; Tiwari, Suresh; Naazneen, Surti

2012-12-01

282

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

283

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

284

Recombinant spider silk particles for controlled delivery of protein drugs  

Microsoft Academic Search

The engineered and recombinant spider silk protein eADF4(C16) has been shown to be a promising biomaterial for the use as drug delivery system. In previous studies, eADF4(C16) particles were loaded with low molecular weight drugs exhibiting a positive net-charge and sufficient hydrophobicity. Here, we demonstrate that also macromolecular drugs like proteins can be loaded on eADF4(C16) particles. Using lysozyme as

Markus Hofer; Gerhard Winter; Julia Myschik

285

Silicon-polymer hybrid materials for drug delivery.  

PubMed

Silicon and its oxides are widely used in biomaterials research, tissue engineering and drug delivery. These materials are highly biocompatible, easily surface functionalized, degrade into nontoxic silicic acid and can be processed into various forms such as micro- and nano-particles, monoliths, membranes and micromachined structures. The large surface area of porous forms of silicon and silica (up to 1200 m2/g) permits high drug loadings. The degradation kinetics of silicon- and silica-based materials can be tailored by coating or grafting with polymers. Incorporation of polymers also improves control over drug-release kinetics. The use of stimuli-responsive polymers has enabled environmental stimuli-triggered drug release. Simultaneously, silicon microfabrication techniques have facilitated the development of sophisticated implantable drug-delivery microdevices. This paper reviews the synthesis, novel properties and biomedical applications of silicon-polymer hybrid materials with particular emphasis on drug delivery. The biocompatible and bioresorptive properties of mesoporous silica and porous silicon make these materials attractive candidates for use in biomedical applications. The combination of polymers with silicon-based materials has generated a large range of novel hybrid materials tailored to applications in localized and systemic drug delivery. PMID:21425994

McInnes, Steven J P; Voelcker, Nicolas H

2009-09-01

286

Gastroretentive floating drug-delivery systems: a critical review.  

PubMed

The oral delivery of drugs with a narrow absorption window in the gastrointestinal tract (GIT) is often limited by poor bioavailability with conventional dosage forms due to incomplete drug release and short residence time at the site of absorption. To overcome this drawback and to maximize the oral absorption of these drugs, gastroretentive systems such as mucoadhesive, high-density, expandable, and floating systems have been developed. These systems provide controlled delivery of drugs with prolonged gastric residence time. However, in humans, differences in various physiological and biological factors can affect the gastric residence time and drug-delivery behavior from gastroretentive systems. Some floating drug-delivery systems (FDDS) have shown the capability to accommodate these variations without affecting drug release. This review mainly focuses on various physiological considerations for development of FDDS, and highlights recent technological developments including new dosage forms and their production techniques (e.g., holt-melt extrusion, melt pelletization, and pulsed plasma-irradiation processes). Alternatives to the existing in vitro compendial methods for evaluating floating dosage forms will be discussed, and a critical analysis of the existing literature on FDDS, identifying the potential areas for future research, is provided. PMID:21395515

Kotreka, Udaya K; Adeyeye, Moji Christianah

2011-01-01

287

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

288

Floating microspheres as drug delivery system: newer approaches.  

PubMed

A controlled drug delivery system with prolonged residence time in the stomach can be of great practical importance for drugs with an absorption window in the upper small intestine. The main limitations are attributed to the inter- and intra-subject variability of gastro-intestinal (GI) transit time and the non-uniformity of drug absorption throughout the alimentary canal. Floating drug delivery systems (FDDSs) are expected to remain buoyant in a lasting way upon the gastric contents and consequently to enhance the bioavailability of drugs. The various buoyant preparations include hollow microspheres, granules, powders, tablets, capsules, pills and laminated films. Floating microspheres are specially gaining attention due to their wide applicability in the targeting of drugs to stomach. These floating microspheres have the advantage that they remain buoyant and distributed uniformly over the gastric fluid to avoid the vagaries of gastric emptying and release the drug for prolonged period of time. A major drawback of low-density floating drug delivery systems is that their performance is strongly dependent upon the gastric emptying process of stomach. Multiparticulate low-density particles can successfully prolong the gastric retention time of drugs. This article is a review of two important approaches utilized to prepare and improve the performance of floating microspheres. PMID:18673266

Jain, Sunil K; Agrawal, Govind P; Jain, Narendra K

2008-07-01

289

The practicality of mesoporous silica nanoparticles as drug delivery devices and progress toward this goal.  

PubMed

Mesoporous silica nanoparticles (MSNs) have been proposed as drug delivery devices for approximately 15 years. The history of in vitro studies has been promising, demonstrating that MSNs have the capability for stimulus-responsive controlled release, good cellular uptake, cell specific targeting, and the ability to carry a variety of cargoes from hydrophobic drug molecules to imaging agents. However, the translation of the in vitro findings to in vivo conditions has been slow. Herein, we review the current state-of-the-art in the use of MSN for systemic drug delivery in vivo and provide critical insight into the future of MSNs as systemic drug delivery devices and directions that should be undertaken to improve their practicality. PMID:24871552

Roggers, Robert; Kanvinde, Shrey; Boonsith, Suthida; Oupický, David

2014-10-01

290

Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: A review  

PubMed Central

Calcium phosphates (CaPs) are the most widely used bone substitutes in bone tissue engineering due to their compositional similarities to bone mineral and excellent biocompatibility. In recent years, CaPs, especially hydroxyapatite and tricalcium phosphate, have attracted significant interest in simultaneous use as bone substitute and drug delivery vehicle, adding a new dimension to their application. CaPs are more biocompatible than many other ceramic and inorganic nanoparticles. Their biocompatibility and variable stoichiometry, thus surface charge density, functionality, and dissolution properties, make them suitable for both drug and growth factor delivery. CaP matrices and scaffolds have been reported to act as delivery vehicles for growth factors and drugs in bone tissue engineering. Local drug delivery in musculoskeletal disorder treatments can address some of the critical issues more effectively and efficiently than the systemic delivery. CaPs are used as coatings on metallic implants, CaP cements, and custom designed scaffolds to treat musculoskeletal disorders. This review highlights some of the current drug and growth factor delivery approaches and critical issues using CaP particles, coatings, cements, and scaffolds towards orthopedic and dental applications. PMID:22127225

Bose, Susmita; Tarafder, Solaiman

2012-01-01

291

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

292

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

293

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

294

Dissolving microneedles for transdermal drug delivery  

Microsoft Academic Search

Microfabrication technology has been adapted to produce micron-scale needles as a safer and painless alternative to hypodermic needle injection, especially for protein biotherapeutics and vaccines. This study presents a design that encapsulates molecules within microneedles that dissolve within the skin for bolus or sustained delivery and leave behind no biohazardous sharp medical waste. A fabrication process was developed based on

Jeong W. Lee; Jung-Hwan Park; Mark R. Prausnitz

2008-01-01

295

Drug-loaded nano-microcapsules delivery system mediated by ultrasound-targeted microbubble destruction: A promising therapy method  

PubMed Central

The nano-microcapsules drug delivery system is currently a promising method for the treatment of many types of diseases, particularly tumors. However, the drug delivery efficiency does not reach a satisfactory level to meet treatment demands. Therefore, the effectiveness of delivery needs to be improved. Based on the alterations in the structure and modification of nano-microcapsules, ultrasound-targeted microbubble destruction (UTMD), a safe physical targeted method, may increase tissue penetration and cell membrane permeability, aiding the drug-loaded nano-microcapsules ingress the interior of targeted tissues and cells. The effectiveness and exact mechanism of action of the drug-loaded nano-microcapsules delivery system mediated by UTMD have yet to be fully elucidated. In this study, the latest advancement in UTMD-mediated drug loaded nano-microcapsules system technology was reviewed and the hindrances of UTMD-mediated drug delivery were assessed, in combination with a prospective study. The findings suggested that the drug delivery efficiency of nano-microcapsules mediated by UTMD was distinctly improved. Thus, the UTMD-mediated drug-loaded nano-microcapsules delivery system may significantly improve the efficiency of drug delivery, which may be a promising new therapeutic method. PMID:24648976

MA, JING; DU, LIAN FANG; CHEN, MING; WANG, HANG HUI; XING, LING XI; JING, LI FANG; LI, YUN HUA

2013-01-01

296

Thermo-responsive Layer-by-Layer Assemblies for Nanoparticle-based Drug Delivery  

E-print Network

Layer-by-layer (LbL) capsules, known for their versatility and smart response to environmental stimuli, have attracted great interest in drug delivery applications. However, achieving a desired drug delivery system with sustained and tunable drug...

Zhou, Jing

2013-11-26

297

Bioactive and bioresponsive nanoparticle surface modifications for vaccine and systemic drug delivery  

E-print Network

the most common transdermal drug delivery device availableuse of a transdermal patch that elutes drugs continuouslytransdermal patch is one of its major advantages. Transmucosal delivery refers to the absorption of a drug

Clawson, Corbin Zean

2011-01-01

298

Hydrogel-Based Colloidal Polymeric System for Protein and Drug Delivery: Physical and Chemical Characterization, Permeability Control and Applications  

Microsoft Academic Search

The use of polymeric nanoparticles as drug carriers is receiving an increasing amount of attention both in academia and industry.\\u000a The development of suitable delivery systems for protein drugs with high molecular weights and short half-lives is of current\\u000a interest. In addition, nanoparticles have a number of potential applications in drug and vaccine delivery as well as gene\\u000a therapy applications.

Ales Prokop; Evgenii Kozlov; Gianluca Carlesso; Jeffrey M. Davidson

299

Status of surfactants as penetration enhancers in transdermal drug delivery.  

PubMed

Surfactants are found in many existing therapeutic, cosmetic, and agro-chemical preparations. In recent years, surfactants have been employed to enhance the permeation rates of several drugs via transdermal route. The application of transdermal route to a wider range of drugs is limited due to significant barrier to penetration across the skin which is associated with the outermost stratum corneum layer. Surfactants have effects on the permeability characteristics of several biological membranes including skin. They have the potential to solubilize lipids within the stratum corneum. The penetration of the surfactant molecule into the lipid lamellae of the stratum corneum is strongly dependent on the partitioning behavior and solubility of surfactant. Surfactants ranging from hydrophobic agents such as oleic acid to hydrophilic sodium lauryl sulfate have been tested as permeation enhancer to improve drug delivery. This article reviews the status of surfactants as permeation enhancer in transdermal drug delivery of various drugs. PMID:22368393

Som, Iti; Bhatia, Kashish; Yasir, Mohd

2012-01-01

300

Status of surfactants as penetration enhancers in transdermal drug delivery  

PubMed Central

Surfactants are found in many existing therapeutic, cosmetic, and agro-chemical preparations. In recent years, surfactants have been employed to enhance the permeation rates of several drugs via transdermal route. The application of transdermal route to a wider range of drugs is limited due to significant barrier to penetration across the skin which is associated with the outermost stratum corneum layer. Surfactants have effects on the permeability characteristics of several biological membranes including skin. They have the potential to solubilize lipids within the stratum corneum. The penetration of the surfactant molecule into the lipid lamellae of the stratum corneum is strongly dependent on the partitioning behavior and solubility of surfactant. Surfactants ranging from hydrophobic agents such as oleic acid to hydrophilic sodium lauryl sulfate have been tested as permeation enhancer to improve drug delivery. This article reviews the status of surfactants as permeation enhancer in transdermal drug delivery of various drugs. PMID:22368393

Som, Iti; Bhatia, Kashish; Yasir, Mohd.

2012-01-01

301

Microneedle-based drug delivery: studies on delivery parameters and biocompatibility  

Microsoft Academic Search

There is a significant interest in the application of microneedles in intradermal drug delivery systems. Previous studies\\u000a have demonstrated that skin permeation of drugs can be increased by orders of magnitude with microneedle insertion. In this\\u000a study, emphasis is placed on the development of low cost, painless intradermal microneedle systems that can enhance the percutaneous\\u000a drug permeation. Microneedles of octagonal

Yan Wu; Yuqin Qiu; Suohui Zhang; Guangjiong Qin; Yunhua Gao

2008-01-01

302

Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy  

PubMed Central

Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy. PMID:24772414

Lohcharoenkal, Warangkana; Wang, Liying; Chen, Yi Charlie

2014-01-01

303

Which drug or drug delivery system can change clinical practice for brain tumor therapy?  

PubMed Central

The prognosis and treatment outcome for primary brain tumors have remained unchanged despite advances in anticancer drug discovery and development. In clinical trials, the majority of promising experimental agents for brain tumors have had limited impact on survival or time to recurrence. These disappointing results are partially explained by the inadequacy of effective drug delivery to the CNS. The impediments posed by the various specialized physiological barriers and active efflux mechanisms lead to drug failure because of inability to reach the desired target at a sufficient concentration. This perspective reviews the leading strategies that aim to improve drug delivery to brain tumors and their likelihood to change clinical practice. The English literature was searched for defined search items. Strategies that use systemic delivery and those that use local delivery are critically reviewed. In addition, challenges posed for drug delivery by combined treatment with anti-angiogenic therapy are outlined. To impact clinical practice and to achieve more than just a limited local control, new drugs and delivery systems must adhere to basic clinical expectations. These include, in addition to an antitumor effect, a verified favorable adverse effects profile, easy introduction into clinical practice, feasibility of repeated or continuous administration, and compatibility of the drug or delivery system with any tumor size and brain location. PMID:23502426

Siegal, Tali

2013-01-01

304

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

305

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.

306

Computational model of local intravascular drug delivery  

E-print Network

Drug-eluting stents (DES) virtually eradicate the clinical phenomena of vessel restenosis; yet, they also increase the short and long term risks for stent thrombosis. To improve their safety and efficacy, it is critical ...

Balakrishnan, Brinda

2007-01-01

307

Constructing tunable nanopores and their application in drug delivery.  

PubMed

Inspired by biological cell membranes, various "smart" and efficient gating nanoporous devices have been proposed to imitate and to understand life processes. Nanodevices under development with enhanced gating efficiency could play pivotal roles in biosensing and drug delivery. In this Perspective, we highlight an important development by Willner and colleagues that is detailed in this issue of ACS Nano. They designed a new "smart" nanodevice with both "sense" and "release" functionalities for drug delivery based on a nanoporous material, mesoporous silica nanoparticles. We outline recent progress in designing intelligently gated nanoporous devices in material science and nanotechnology. We also summarize new strategies designed for drug delivery based on mesoporous materials. With continuing efforts, we expect more powerful nanodevices to be developed and used in clinical and other real-word applications. PMID:24143925

Duan, Ruixue; Xia, Fan; Jiang, Lei

2013-10-22

308

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

309

Synthesis of the KMB-Drug Delivery Carrier  

NASA Astrophysics Data System (ADS)

Purified konjac glucomannan(KGM) was blended with Xanthan gum to prepared gel, which was valued by its viscosity and tenacity. The konjac micro-balls(KMBs) were prepared in drying and wetting method respectively. The diameter of the KMBs was analyzed with laser particle size analyzer. To a carrier of drug deliver, the delivery characteristics of the NMP, which embedded in KMB, was discussed. The results showed that KMB was well dispersed in DMSO, and its diameter was 4.08 ?m. In paraffin, KMB was homogeneous disperse with diameter(2.23 ?m). In the behavior of drug delivery, the characteristics of drug sustained-release were obvious, and the delivery time was more than 24 h.

Wang, Chao; Xu, Mei; Zhu, Yu-peng; Zhang, Wei-hua; Gong, Yuan-yuan; Li, Dong-sheng

310

Ocular Drug Delivery; Impact of in vitro Cell Culture Models  

PubMed Central

Normal vision depends on the optimal function of ocular barriers and intact membranes that selectively regulate the environment of ocular tissues. Novel pharmacotherapeutic modalities have aimed to overcome such biological barriers which impede efficient ocular drug delivery. To determine the impact of ocular barriers on research related to ophthalmic drug delivery and targeting, herein we provide a review of the literature on isolated primary or immortalized cell culture models which can be used for evaluation of ocular barriers. In vitro cell cultures are valuable tools which serve investigations on ocular barriers such as corneal and conjunctival epithelium, retinal pigment epithelium and retinal capillary endothelium, and can provide platforms for further investigations. Ocular barrier-based cell culture systems can be simply set up and used for drug delivery and targeting purposes as well as for pathological and toxicological research. PMID:23198080

Barar, Jaleh; Asadi, Masoud; Mortazavi-Tabatabaei, Seyed Abdolreza; Omidi, Yadollah

2009-01-01

311

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

312

Tripartite complex for axonal transport drug delivery achieves pharmacological effect  

Microsoft Academic Search

BACKGROUND: Targeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System) neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy

Aaron G Filler; Garth T Whiteside; Mark Bacon; Martyn Frederickson; Franklyn A Howe; Miri D Rabinowitz; Alan J Sokoloff; Terrence W Deacon; Chris Abell; Raj Munglani; John R Griffiths; B Anthony Bell; Andrew ML Lever

2010-01-01

313

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

314

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; Dionisio, Marita; Remunan Lopez, Carmen; Grenha, Ana

2012-01-01

315

Ultrasound-Mediated Local Drug and Gene Delivery Using Nanocarriers  

PubMed Central

With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers. PMID:25202710

Zhou, Qiu-Lan; Chen, Zhi-Yi; Yang, Feng

2014-01-01

316

Interpenetrating Polymer Networks as Innovative Drug Delivery Systems  

PubMed Central

Polymers have always been valuable excipients in conventional dosage forms, also have shown excellent performance into the parenteral arena, and are now capable of offering advanced and sophisticated functions such as controlled drug release and drug targeting. Advances in polymer science have led to the development of several novel drug delivery systems. Interpenetrating polymer networks (IPNs) have shown superior performances over the conventional individual polymers and, consequently, the ranges of applications have grown rapidly for such class of materials. The advanced properties of IPNs like swelling capacity, stability, biocompatibility, nontoxicity and biodegradability have attracted considerable attention in pharmaceutical field especially in delivering bioactive molecules to the target site. In the past few years various research reports on the IPN based delivery systems showed that these carriers have emerged as a novel carrier in controlled drug delivery. The present review encompasses IPNs, their types, method of synthesis, factors which affects the morphology of IPNs, extensively studied IPN based drug delivery systems, and some natural polymers widely used for IPNs. PMID:24949205

Lohani, Alka; Singh, Garima; Bhattacharya, Shiv Sankar; Verma, Anurag

2014-01-01

317

Delivery of aerosolized drugs encapsulated in liposomes  

SciTech Connect

Mycobacterium tuberculosis (Mtb) is an infectious disease that resides in the human lung. Due to the difficulty in completely killing off the disease in infected individuals, Mtb has developed drug-resistant forms and is on the rise in the human population. Therefore, ITRI and the University of New Mexico are collaborating to explore the treatment of Mtb by an aerosolized drug delivered directly to the lungs. In conclusion, it is feasible to obtain an appropriate size and concentration of the liposomes before and after aerosolization.

Cheng, Yung-Sung; Lyons, C.R. [Univ. of New Mexico, Albuquerque, NM (United States); Schmid, M.H.

1995-12-01

318

Physicochemical investigations of a drug delivery oscillator  

E-print Network

diffuse out of membrane causing it to swell again. 4. System is poised to repeat step 1. Purpose: To identify the factors that prevent sustained oscillations of constant period and amplitude in a glucose-driven hormone delivery device. Methods... to change in pH. Saline containing constant glucose concentration flows through donor cell at pH=7.4. The receptor cell contains enzymes- glucose oxidase and catalase along with a piece of marble, which acts as a proton shunt. pH change is followed...

Bhalla, A. S.; Siegel, R. A.

2006-10-27

319

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

320

Effective use of transdermal drug delivery in children.  

PubMed

Transdermal administration offers a non-invasive and convenient method for paediatric drug delivery. The competent skin barrier function in term infants and older children limits both water loss and the percutaneous entry of chemicals including drugs; but the smaller doses required by children eases the attainment of therapeutic concentrations. Transdermal patches used in paediatrics include fentanyl, buprenorphine, clonidine, scopolamine, methylphenidate, oestrogens, nicotine and tulobuterol. Some patches have paediatric labelling supported by clinical trials whereas others are used unlicensed. Innovative drug delivery methods, such as microneedles and sonophoresis are being tested for their safety and efficacy; needleless injectors are primarily used to administer growth hormone; and two iontophoretic devices were approved for paediatrics. In contrast, the immature and rapidly evolving skin barrier function in premature neonates represents a significant formulation challenge. Unfortunately, this population group suffers from an absence of approved transdermal formulations, a shortcoming exacerbated by the significant risk of excessive drug exposure via the incompletely formed skin barrier. PMID:24333231

Delgado-Charro, M Begoña; Guy, Richard H

2014-06-01

321

Advances in topical drug delivery system: micro to nanofibrous structures.  

PubMed

This paper is a review of the latest developments in the field of topical drug delivery via which the drug is directly applied onto the skin with high selectivity and efficiency. Advances in microfiber-based medical textiles such as sutures and wound dressings, especially those containing a drug or an antimicrobial agent, have been covered briefly. A special focus is on recent developments in the area of nanofibrous drug delivery systems, which have several advantages due to their large surface area to volume ratio, high porosity and flexibility. The electrospinning technique to produce nanofibers has also been discussed with reference to latest advances such as multiple needles, needleless and coaxial forms of electrospinning. The applications of nanofibers in different areas such as wound dressing, periodontal and anticancer treatment have also been discussed. PMID:24730303

Joshi, Mangala; Butola, B S; Saha, Kasturi

2014-01-01

322

Nanotechnology in Drug Delivery and Tissue Engineering: From Discovery to Applications  

PubMed Central

The application of nanotechnology in medicine, referred to as nanomedicine, is offering numerous exciting possibilities in healthcare. Herein, we discuss two important aspects of nanomedicine—drug delivery and tissue engineering—highlighting the advances we have recently experienced, the challenges we are currently facing, and what we are likely to witness in the near future. PMID:20726522

Shi, Jinjun; Votruba, Alexander R.; Farokhzad, Omid C.; Langer, Robert

2010-01-01

323

Ultrasound-triggered drug delivery using acoustic droplet vaporization  

NASA Astrophysics Data System (ADS)

The goal of targeted drug delivery is the spatial and temporal localization of a therapeutic agent and its associated bioeffects. One method of drug localization is acoustic droplet vaporization (ADV), whereby drug-laden perfluorocarbon (PFC) emulsions are vaporized into gas bubbles using ultrasound, thereby releasing drug locally. Transpulmonary droplets are converted into bubbles that occlude capillaries, sequestering the released drug within an organ or tumor. This research investigates the relationship between the ADV and inertial cavitation (IC) thresholds---relevant for drug delivery due to the bioffects generated by IC---and explores the delivery of lipophilic and hydrophilic compounds using PFC double emulsions. IC can positively and negatively affect ultrasound mediated drug delivery. The ADV and IC thresholds were determined for various bulk fluid, droplet, and acoustic parameters. At 3.5 MHz, the ADV threshold occurred at a lower rarefactional pressure than the IC threshold. The results suggest that ADV is a distinct phenomenon from IC, the ADV nucleus is internal to the droplet, and the IC nucleus is the bubble generated by ADV. The ADV triggered release of a lipophilic chemotherapeutic agent, chlorambucil (CHL), from a PFC-in-oil-in-water emulsion was explored using plated cells. Cells exposed to a CHL-loaded emulsion, without ADV, displayed 44% less growth inhibition than cells exposed to an equal concentration of CHL in solution. Upon ADV of the CHL-loaded emulsion, the growth inhibition increased to the same level as cells exposed to CHL in solution. A triblock copolymer was synthesized which enabled the formulation of stable water-in-PFC-in-water (W1/PFC/W2) emulsions. The encapsulation of fluorescein in the W1 phase significantly decreased the mass flux of fluorescein; ADV was shown to completely release the fluorescein from the emulsions. ADV was also shown to release thrombin, dissolved in the W1 phase, which could be used in vivo to extend synergistically the duration of ADV-generated, microbubble-based embolizations. Overall, the results suggest that PFC double emulsions can be used as an ultrasound-triggered drug delivery system. Compared to traditional drug delivery systems, ADV could be used to increase the therapeutic efficacy and decrease the systemic toxicity of drug therapy.

Fabiilli, Mario Leonardo

324

Self-Assembling Peptide Amphiphiles for Targeted Drug Delivery  

NASA Astrophysics Data System (ADS)

The systemic delivery of therapeutics is currently limited by off-target side effects and poor drug uptake into the cells that need to be treated. One way to circumvent these issues is to target the delivery and release of therapeutics to the desired location while limiting systemic toxicity. Using self-assembling peptide amphiphiles (PAs), this work has investigated supramolecular nanostructures for the development of targeted therapies. Specifically, the research has focused on the interrelationships between presentation of targeting moeities and the control of nanostructure morphology in the context of systemic delivery for targeting cancer and vascular injuries. The self-assembly region of the PA was systematically altered to achieve control of nanostructure widths, from 100 nm to 10 nm, by the addition of valine-glutamic acid dimers into the chemical structure, subsequently increasing the degree of nanostructure twist. For the targeting of tumors, a homing PA was synthesized to include a dimeric, cyclic peptide sequence known to target the cancer-specific, death receptor 5 (DR5) and initiate apoptosis through the oligomerization of DR5. This PA presented a multivalent display of DR5-binding peptides, resulting in improved binding affinity measured by surface plasmon resonance. The DR5-targeting PA also showed enhanced efficacy in both in vitro and in vivo tumor models relative to non-targeted controls. Alternative modifications to the PA-based antitumor therapies included the use of a cytotoxic, membrane-lytic PA coassembled with a pegylated PA, which showed enhanced biodistribution and in vivo activity after coassembly. The functionalization of the hydrophobic core was also accomplished through the encapsulation of the chemotherapy camptothecin, which was shown to be an effective treatment in vivo. Additionally, a targeted PA nanostructure was designed to bind to the site of vascular intervention by targeting collagen IV. Following balloon angioplasty, targeted PA nanofibers showed enhanced binding by fluorescence relative to spherical micelles with the same targeting sequence, demonstrating the importance of nanostructure shape for vascular binding. Nitric oxide was functionalized onto the PA nanostructure through the S-nitrosylation (SNO) of a cysteine residue. Two weeks after vascular injury, the SNO-functionalized, targeted nanofibers showed significantly decreased levels of restenosis. In all treatment methods described, the control of multivalency through the tuning of supramolecular structure was essential to achieve optimal binding. Understanding the role of dynamic, supramolecular structures for the systemic delivery of peptide therapeutics should be an important focus of future work.

Moyer, Tyson

325

Proniosomes as a drug carrier for transdermal delivery of ketorolac  

Microsoft Academic Search

Niosomes are nonionic surfactant vesicles that have potential applications in the delivery of hydrophobic and hydrophilic drugs. Permeation of a potent nonsteroidal anti-inflammatory, ketorolac, across excised rabbit skin from various proniosome gel formulations was investigated using Franz diffusion cells. Each of the prepared proniosomes significantly improved drug permeation and reduced the lag time (P<0.05). Proniosomes prepared with Span 60 provided

Ibrahim A. Alsarra; A. A. Bosela; S. M. Ahmed; G. M. Mahrous

2005-01-01

326

Drug delivery with carbon nanotubes for in vivo cancer treatment  

Microsoft Academic Search

Chemically functionalized single-walled carbon nanotubes (SWNTs) have shown promise in tumor targeted accumulation in mice and exhibit biocompatibility, excretion and little toxicity. Here, we demonstrate in-vivo SWNT drug delivery for tumor suppression in mice. We conjugate paclitaxel (PTX), a widely used cancer chemotherapy drug to branched polyethylene-glycol (PEG) chains on SWNTs via a cleavable ester bond to obtain a water

Zhuang Liu; Kai Chen; Corrine Davis; Sarah Sherlock; Qizhen Cao; Hongjie Dai

2008-01-01

327

Modeling of transdermal drug delivery with a microneedle array  

NASA Astrophysics Data System (ADS)

Transdermal drug delivery is generally limited by the extraordinary barrier properties of the stratum corneum, the outer 10-15 µm layer of skin. A conventional needle inserted across this barrier and into deeper tissues could effectively deliver drugs. However, it would lead to infection and cause pain, thereby reducing patient compliance. In order to administer a frequent injection of insulin and other therapeutic agents more efficiently, integrated arrays with very short microneedles were recently proposed as very good candidates for painless injection or extraction. A variety of microneedle designs have thus been made available by employing the fabrication tools of the microelectronics industry and using materials such as silicon, metals, polymers and glass with feature sizes ranging from sub-micron to nanometers. At the same time, experiments were also made to test the capability of the microneedles to inject drugs into tissues. However, due to the difficulty encountered in measurement, a detailed understanding of the spatial and transient drug delivery process still remains unclear up to now. To better grasp the mechanisms involved, quantitative theoretical models were developed in this paper to simultaneously characterize the flow and drug transport, and numerical solutions were performed to predict the kinetics of dispersed drugs injected into the skin from a microneedle array. Calculations indicated that increasing the initial injection velocity and accelerating the blood circulation in skin tissue with high porosity are helpful to enhance the transdermal drug delivery. This study provides the first quantitative simulation of fluid injection through a microneedle array and drug species transport inside the skin. The modeling strategy can also possibly be extended to deal with a wider range of clinical issues such as targeted nanoparticle delivery for therapeutics or molecular imaging.

Lv, Y.-G.; Liu, J.; Gao, Y.-H.; Xu, B.

2006-11-01

328

Processing of Polymer Nanofibers Through Electrospinning as Drug Delivery Systems  

Microsoft Academic Search

The use of electrospun fibers as drug carriers could be promising in the future for biomedical applications, especially postoperative\\u000a local chemotherapy. In this research, electrospun fibers were developed as a new system for the delivery of ketoprofen as\\u000a non-steroidal anti-inflammatory drug (NSAID). The fibers were made either from polycaprolactone (PCL) as a biodegradable polymer\\u000a or polyurethane (PU) as a non-biodegradable

E. Kenawy; F. I. Abdel-Hay; M. H. El-Newehy; G. E. Wnek

329

Processing of Polymer Nanofibers Through Electrospinning as Drug Delivery Systems  

Microsoft Academic Search

The use of electrospun fibers as drug carriers could be promising in the future for biomedical applications, especially postoperative local chemotherapy. In this research, electrospun fibers were developed as a new system for the delivery of ketoprofen as non-steroidal anti-inflammatory drug (NSAID). The fibers were made either from polycaprolactone (PCL) as a biodegradable polymer or polyurethane (PU) as a non-biodegradable

E. Kenawy; F. I. Abdel-Hay; M. H. El-Newehy; G. E. Wnek

2009-01-01

330

Application of fused deposition modelling in controlled drug delivery devices  

Microsoft Academic Search

Purpose – This paper seeks to present an investigation on building controlled drug delivery device (DDD) matrix using fused deposition modelling (FDM) rapid prototyping (RP) process. The focus of the study is on the effect of FDM fabricated macro-features of reservoir-matrix DDD models on the drug release rates through the diffusion process. Design\\/methodology\\/approach – Using various parameters involved with FDM,

S. H. Masood

2007-01-01

331

Design of dendrimer-based drug delivery nanodevices with enhanced therapeutic efficacies  

NASA Astrophysics Data System (ADS)

Dendrimers and hyperbranched polymers possess highly branched architectures, with a large number of controllable, tailorable, `peripheral' functionalities. Since the surface chemistry of these materials can be modified with relative ease, these materials have tremendous potential in targeted drug delivery. They have significant potential compared to liposomes and nanoparticles, because of the reduced macrophage update, increased cellular transport, and the ability to modulate the local environment through functional groups. We are developing nanodevices based on dendritic systems for drug delivery, that contain a high drug payload, ligands, and imaging agents, resulting in `smart' drug delivery devices that can target, deliver, and signal. In collaboration with the Children's Hospital of Michigan, Karmanos Cancer Institute, and College of Pharmacy, we are testing the in vitro and in vivo response of these nanodevices, by adapting the chemistry for specific clinical applications such as asthma and cancer. These materials are characterized by UV/Vis spectroscopy, flow cytometry, fluorescence/confocal microscopy, and appropriate animal models. Our results suggest that: (1) We can prepare drug-dendrimer conjugates with drug payloads of greater than 50%, for a variety of drugs; (2) The dendritic polymers are capable of transporting and delivering drugs into cells faster than free drugs, with superior therapeutic efficiency. This can be modulated by the surface functionality of the dendrimer; (3) For chemotherapy drugs, the conjugates are a factor of 6-20 times more effective even in drug-resistant cell lines; (4) For corticosteroidal drugs, the dendritic polymers provide higher drug residence times in the lung, allowing for passive targeting. The ability of the drug-dendrimer-ligand conjugates to target specific asthma and cancer cells is currently being explored using in vitro and in vivo animal models.

Kannan, Rangaramanujam

2007-03-01

332

N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: Glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population  

PubMed Central

Background: Innovative Vision Products, Inc. (IVP)’s scientists developed the lubricant eye drops (Can-C™) designed as 1% N-acetylcarnosine (NAC) prodrug of l-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a sustained drug delivery system. Only the natural l-isomeric form of NAC raw material was specifically synthesized at the cGMP facility and employed for the manufacturing of Can-C™ eye drops. Objective and study design: In the present clinical study the authors assessed vision before and after 9 month term of topical ocular administration of NAC lubricant eye drops or placebo in 75 symptomatic patients with age-related uncomplicated cataracts in one or both eyes, with acuity in one eye of 20/40 or worse (best-corrected distance), and no previous cataract surgery in either eye and no other ocular abnormality and 72 noncataract subjects ranged in age from 54 to 78 years. Setting: Subjects in these subsample groups have reported complaints of glare and wanted to administer eye drops to get quick eye relief and quality of vision for their daily activities including driving and computer works. Following 9 months of treatment with NAC lubricant eye drops, most patients’ glare scores were improved or returned to normal in disability glare tests with Halometer DG. Improvement in disability glare was accompanied with independent improvement in acuity. Furthermore, patients with the poorest pretreatment vision were as likely to regain certain better visual function after 9 months of treatment with N-acetylcarnosine lubricant eye drops as those with the worth pretreatment vision. Patients or other participants: The authors made a reference to electronic records of the product sales to patients who have been made the repurchase of the Can-C™ eye drops since December 2001. Intervention: Based on this analysis of recorded adjustments to inventory, various parameters were analyzed during the continued repurchase behavior program, including testimonials from buyers. With these figures, researchers judged on the patients’ compliance rate to self-administer NAC eye-drops. Main outcome measure and results: The ophthalmic drug showed potential for the non-surgical treatment of age-related cataracts for participants after controlling for age, gender and daily activities and on a combined basis of repurchases behavior reports in more than 50,000 various cohort survivors, has been demonstrated to have a high efficacy and good tolerability for prevention and treatment of visual impairment determined for the older population with relative stable pattern of causes for blindness and visual impairment. The mechanisms of prevention and reversal of cataracts with NAC ophthalmic drug are considered which include prevention by the intraocular released carnosine of free-radical-induced inactivation of proprietary lens antioxidant enzymes (superoxide dismutase); prevention of carbohydrate and metal-catalyzed autooxidation of ascorbic acid-induced cross-linking glycation reactions to the lens proteins; transglycation properties of carnosine, allowing it to compete for the glycating agent, protecting proteins (lens crystallins) against modification; universal antioxidant and scavenging activity towards lipid hydroperoxides, aldehydes and oxygen radicals; activation with l-carnosine ingredient of proteasome activity in the lens; chaperone-like disaggregating to lens crystallins activity of NAC and of its bioactivated principal carnosine. Blindness incidence increased with advancing age, such as cataract and glaucoma, which are by far the commonest causes of blindness in our sample and in all age groups, glaucomatous neurodegeneration can be treated with developed NAC autoinduction prodrug eye drops equipped with corneal absorption promoters. The common blinding affections presenting in developed countries such as, senile macular degeneration, hereditary chorioretinal dystrophies, diabetic retinopathy are poorly represented in our current summary of vital

Babizhayev, Mark A; Burke, Leslie; Micans, Philip; Richer, Stuart P

2009-01-01

333

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

334

Drug delivery to the inner ear  

NASA Astrophysics Data System (ADS)

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.

Wise, Andrew K.; Gillespie, Lisa N.

2012-12-01

335

Photosensitizer Drug Delivery via an Optical Fiber  

PubMed Central

An optical fiber has been developed with a maneuverable mini-probe tip that sparges O2 gas and photo-detaches pheophorbide (sensitizer) molecules. Singlet oxygen is produced at the probe tip surface which reacts with an alkene spacer group releasing sensitizer upon fragmentation of a dioxetane intermediate. Optimal sensitizer photorelease occurred when the probe tip was loaded with 60 nmol sensitizer, where crowding of the pheophorbide molecules and self-quenching were kept to a minimum. The fiber optic tip delivered pheophorbide molecules and singlet oxygen to discrete locations. 60 nmol sensitizer was delivered into petrolatum; however, sensitizer release was less efficient in toluene-d8 (3.6 nmol) where most had remained adsorbed on the probe tip, even after the covalent alkene spacer bond had been broken. The results open the door to a new area of fiber optic-guided sensitizer delivery for the potential photodynamic therapy of hypoxic structures requiring cytotoxic control. PMID:21539365

Zamadar, Matibur; Ghosh, Goutam; Mahendran, Adaickapillai; Minnis, Mihaela; Kruft, Bonnie I.; Ghogare, Ashwini; Aebisher, David; Greer, Alexander

2012-01-01

336

Protein Drug Delivery and Formulation Development  

Microsoft Academic Search

\\u000a Several therapeutic agents including low and high molecular weight drugs intended for treating back of the eye disorders are\\u000a routinely administered as intravitreal injections. Intravitreal injection of Lucentis®, a therapeutic protein, was approved in 2006 for treating the wet form of age-related macular degeneration. This chapter\\u000a summarizes the challenges and opportunities in delivering therapeutic proteins to the eye. Specifically, barriers

Rinku Baid; Puneet Tyagi; Shelley A. Durazo; Uday B. Kompella

337

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

338

An Implantable MEMS Micropump System for Drug Delivery in Small Animals  

PubMed Central

We present the first implantable drug delivery system for controlled dosing, timing, and location in small animals. Current implantable drug delivery devices do not provide control over these factors or are not feasible for implantation in research animals as small as mice. Our system utilizes an integrated electrolysis micropump, is refillable, has an inert drug reservoir for broad drug compatibility, and is capable of adjustment to the delivery regimen while implanted. Electrochemical impedance spectroscopy (EIS) was used for characterization of electrodes on glass substrate and a flexible Parylene substrate. Benchtop testing of the electrolysis actuator resulted in flow rates from 1 to 34 ?L/min on glass substrate and up to 6.8 ?L/min on Parylene substrate. The fully integrated system generated a flow rate of 4.72 ± 0.35 ?L/min under applied constant current of 1.0 mA while maintaining a power consumption of only ~3 mW. Finally, we demonstrated in vivo application of the system for anti-cancer drug delivery in mice. PMID:22273985

Gensler, Heidi; Sheybani, Roya; Li, Po-Ying; Lo, Ronalee; Meng, Ellis

2012-01-01

339

The ophthalmic rod: a new ophthalmic drug delivery system I.  

PubMed

The ophthalmic rod (OR) is a new drug delivery system, intended as an alternative to conventional therapy in ophthalmology. The rod is made of a nontoxic plastic. It is dipped into a drug solution which after drying forms a thin homogeneous coating. The OR is then packed and sterilized by gamma radiation. The effects of radiation on the contents of the drugs were studied using IR, UV, and thin-layer chromatography (TLC). Sterility, dose variation, and simulated drug delivery in vitro were tested. Pure drugs were used; no preservatives were included. To deliver the drug, the tip of the rod is introduced into the conjunctival sac and rubbed against the palpebral conjunctiva of the lower lid. ORs with tropicamide, oxybuprocaine HCl, pilocarpine HCl, and fluorescein sodium were used. The behavior of the drugs administered by this system was compared with eyedrops. Results of trials with three drugs, i.e., tropicamide, oxybuprocaine HCl, and fluorescein sodium on ORs applied to the eyes of humans and those of the rabbit are discussed. PMID:2205544

Alani, S D

1990-01-01

340

Drug Delivery Into the Eye With the Use of Ultrasound  

E-print Network

duration of 5 minutes. The aqueous humor concentration of a topically applied hydrophilic dye, sodium, Seattle, WA 98105 USA. E-mail: vesna@u.washington.edu. Abbreviations DPBS, Dulbecco's phosphate such as dexamethasone.4 In addi- tion, increasing the efficiency of transcorneal drug delivery may be important

Clark, John

341

Biodegradable polymer microneedles: Fabrication, mechanics and transdermal drug delivery  

Microsoft Academic Search

To overcome the skin's barrier properties that block transdermal delivery of most drugs, arrays of microscopic needles have been microfabricated primarily out of silicon or metal. This study addresses microneedles made of biocompatible and biodegradable polymers, which are expected to improve safety and manufacturability. To make biodegradable polymer microneedles with sharp tips, micro-electromechanical masking and etching were adapted to produce

Jung-Hwan Park; Mark G. Allen; Mark R. Prausnitz

2005-01-01

342

Sugar Micro Needles as Transdermic Drug Delivery System  

Microsoft Academic Search

We designed and fabricated an array of sugar micro needles of the length ranging from 150 ? m to 2 mm for transdermic delivery of drugs. Micro needles were molded out of maltose mixed with pharmaceutical material, being expected bio-degradable in the human skin. To test basic tolerance to the healthy human skin, a clinical experiment was carried out for

Takaya Miyano; Yoshikazu Tobinaga; Takahiro Kanno; Yasushi Matsuzaki; Hitoshi Takeda; Makoto Wakui; Katsumi Hanada

2005-01-01

343

Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery  

Microsoft Academic Search

To overcome skin's barrier properties that block transdermal delivery of most drugs, we and others have microfabricated arrays of microscopic needles, primarily out of silicon or metal. This study addresses microneedles made of biocompatible and biodegradable polymers, which are expected to improve safety and manufacturability. To make biodegradable polymer microneedles with sharp tips, we adapted microelectromechanical masking and etching to

Jung-Hwan Park; Mark G. Allen; Mark R. Prausnitz

2004-01-01

344

[Drug delivery systems using nano-sized drug carriers].  

PubMed

Nanotechnology has attracted great attention all over the world in recent several years and has led to the establishment of the novel technical field of "nanomedicine" through collaboration with advanced medical technology. Particularly, site-specific drug targeting using particle drug carrier systems has made substantial progress and been actively developed. This review explains the essential factors (size and chemical character) of drug carriers to allow long circulation in the bloodstream avoiding the reticuloendothelial system, and shows the present status and future perspective of several types of nano-carrier systems (water-soluble polymer, liposome and polymeric micelle). We also introduce the novel concept of multi-targeting system (combination of two or more targeting methodologies) for ideal drug therapies. PMID:16044950

Nakayama, Masamichi; Okano, Teruo

2005-07-01

345

Tri-partite complex for axonal transport drug delivery achieves pharmacological effect  

PubMed Central

Background Targeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System) neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior. Results We developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle. Conclusion Specific targeting of selected subpopulations of CNS neurons for drug delivery by axonal transport holds great promise. The data shown here provide a basic framework for the intraneural pharmacology of this tripartite complex. The pharmacologically efficacious drug delivery demonstrated here verify the fundamental feasibility of using axonal transport for targeted drug delivery. PMID:20085661

2010-01-01

346

Development and characterization of chronomodulated drug delivery system of captopril  

PubMed Central

Background: Hypertension shows circadian rhythm that there is a rise in pressure from the time of waking or before (about 4 to 8 a.m.), in most people. Conventional drug delivery system of captopril is inappropriate for the delivery of drug, as they cannot be administered just before the symptoms are worsened, because during this time the patients are asleep, bedtime dosing of captopril will not provide a therapeutic plasma drug concentration at the early hours of morning because of poor pharmacokinetic profile and shorter half-life of 1.9 hours. Thus, this study attempts to design and evaluate a chronomodulated pulsatile drug delivery system of captopril which was aimed to release the drug after a lag time of 6 hours. Materials and Methods: Present delivery system was prepared by rupturable coating method. The core containing captopril as a bioactive compound were prepared by direct compression method and then coated sequentially with an inner swelling layer containing hydrocolloid HPMC E5 and an outer rupturable layer consisted of Eudragit RL/RS (1 : 1). Total 12 formulations with different levels of inner swelling layer and outer polymeric layer were prepared and subjected to various processing and formulative parameters like the effect of core composition, level of swelling layer, and rupturable coating on lag time was investigated. In vitro drug release and rupture tests were performed using United States Pharmacopoeia paddle method at 50 rpm in 0.1N HCl and phosphate buffer of pH 6.8. Results: The results showed that as the amount of inner swelling layer increases, the lag time decreases and as the Eudragit coating level increases, the lag time increases and percent water uptake of time-dependent pulsatile release system decreases. The presence of an osmotic agent and effervescent agent helped in shortening of lag time. Conclusion: The system was found to be satisfactory in terms of release of the drug after the lag time of 6 hours. PMID:23071948

Patil, Archana S; Dandagi, Panchaxari M; Masthiholimath, Vinayak S; Gadad, Anand P; Najwade, Basavaraj K

2011-01-01

347

Imaging and drug delivery using theranostic nanoparticles?  

PubMed Central

Nanoparticle technologies are significantly impacting the development of both therapeutic and diagnostic agents. At the intersection between treatment and diagnosis, interest has grown in combining both paradigms into clinically effective formulations. This concept, recently coined as theranostics, is highly relevant to agents that target molecular biomarkers of disease and is expected to contribute to personalized medicine. Here we review state-of-the-art nanoparticles from a therapeutic and a diagnostic perspective and discuss challenges in bringing these fields together. Major classes of nanoparticles include, drug conjugates and complexes, dendrimers, vesicles, micelles, core–shell particles, microbubbles, and carbon nanotubes. Most of these formulations have been described as carriers of either drugs or contrast agents. To observe these formulations and their interactions with disease, a variety of contrast agents have been used, including optically active small molecules, metals and metal oxides, ultrasonic contrast agents, and radionuclides. The opportunity to rapidly assess and adjust treatment to the needs of the individual offers potential advantages that will spur the development of theranostic agents. PMID:20709124

MacKay, J. Andrew

2013-01-01

348

Substituted amylose matrices for oral drug delivery  

NASA Astrophysics Data System (ADS)

High amylose corn starch was used to obtain substituted amylose (SA) polymers by chemically modifying hydroxyl groups by an etherification process using 1,2-epoxypropanol. Tablets for drug-controlled release were prepared by direct compression and their release properties assessed by an in vitro dissolution test (USP XXIII no 2). The polymer swelling was characterized by measuring gravimetrically the water uptake ability of polymer tablets. SA hydrophilic matrix tablets present sequentially a burst effect, typical of hydrophilic matrices, and a near constant release, typical of reservoir systems. After the burst effect, surface pores disappear progressively by molecular association of amylose chains; this allows the creation of a polymer layer acting as a diffusion barrier and explains the peculiar behaviour of SA polymers. Several formulation parameters such as compression force, drug loading, tablet weight and insoluble diluent concentration were investigated. On the other hand, tablet thickness, scanning electron microscope analysis and mercury intrusion porosimetry showed that the high crushing strength values observed for SA tablets were due to an unusual melting process occurring during tabletting although the tablet external layer went only through densification, deformation and partial melting. In contrast, HPMC tablets did not show any traces of a melting process.

Moghadam, S. H.; Wang, H. W.; Saddar El-Leithy, E.; Chebli, C.; Cartilier, L.

2007-03-01

349

Swellable drug-polyelectrolyte matrices (SDPM). Characterization and delivery properties.  

PubMed

The objective of the study is to develop and characterize the delivery properties of swellable drug-polyelectrolyte matrices (SDPM). Solid complexes (C-D)X of carbomer (C) neutralized with different proportions of model basic drugs (D), in which D is atenolol, lidocaine, and metoclopramide, and X=25, 50, 75 and 100 mol of D per 100 equivalents of carboxylic groups of C, were prepared and characterized by DSC-TG, IR, and X-ray diffraction studies. Mechanistic studies with hydrophilic and hydrophobic basic drugs were conducted to explore the drug release patterns of SDPM. Besides, release and up-take studies were carried out in water and NaCl solution to examine the influence of ionic effects. The authors concluded that drugs can be loaded in a high proportion on to the polymer and therefore the resulting (C-D) material could be diluted with other polymers to modulate delivery properties of SDPM. Matrices of atenolol and lidocaine exhibited robust delivery properties with regard to change in proportion of loading D. PMID:15607261

Jimenez-Kairuz, Alvaro Federico; Llabot, Juan Manuel; Allemandi, Daniel Alberto; Manzo, Ruben Hilario

2005-01-01

350

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

351

Prostate cancer relevant antigens and enzymes for targeted drug delivery.  

PubMed

Chemotherapy is one of the most widely used approaches in combating advanced prostate cancer, but its therapeutic efficacy is usually insufficient due to poor specificity and associated toxicity. Lack of targeted delivery to prostate cancer cells is also the primary obstacles in achieving feasible therapeutic effect of other promising agents including peptide, protein, and nucleic acid. Consequently, there remains a critical need for strategies to increase the selectivity of anti-prostate cancer agents. This review will focus on various prostate cancer-relevant antigens and enzymes that could be exploited for prostate cancer targeted drug delivery. Among various targeting strategies, active targeting is the most advanced approach to specifically deliver drugs to their designated cancer cells. In this approach, drug carriers are modified with targeting ligands that can specifically bind to prostate cancer-specific antigens. Moreover, there are several specific enzymes in the tumor microenvironment of prostate cancer that can be exploited for stimulus-responsive drug delivery systems. These systems can specifically release the active drug in the tumor microenvironment of prostate cancer, leading to enhanced tumor penetration efficiency. PMID:24878184

Barve, Ashutosh; Jin, Wei; Cheng, Kun

2014-08-10

352

Soft-Template-Synthesized Mesoporous Carbon for Oral Drug Delivery  

SciTech Connect

Template-synthesized mesoporous carbons were successfully used in in vitro investigations of controlled delivery of three model drugs, captopril, furosemide, and ranitidine hydrochloride. Captopril and furosemide exhibited desorption kinetics over 30 40 h, and ranitidine HCl had a complete release time of 5 10 h. As evident from the slow release kinetics, we contend that our mesoporous carbon is an improved drug-delivery medium compared to state-of-the-art porous silica-based substrates. The mesoporous carbons, synthesized from phloroglucinol and lignin, a synthetic and a sustainable precursor, respectively, exhibit BET surface area of 200 400 m2 g-1 and pore volume of 0.2 0.6 cm3 g-1. The phloroglucinol-based carbon has narrower pore widths and higher pore volume than the lignin-derived counterpart and maintains a longer release time. Numerical modeling of the release kinetics data reveals that the diffusivities of all the drugs from lignin-based carbon media are of equivalent magnitude (10-22 to 10-24 m2 s-1). However, a tailored reduction of pore width in the sorbent reduces the diffusivity of smaller drug molecules (captopril) by an order of magnitude. Thus, engineered pore morphology in our synthesized carbon sorbent, along with its potential to tailor the chemistry of its interaction with sorbet, can be exploited for optimal delivery system of a preferred drug within its therapeutic level and below the level of toxicity.

Saha, Dipendu [ORNL] [ORNL; Warren, Kaitlyn E [ORNL] [ORNL; Naskar, Amit K [ORNL] [ORNL

2014-01-01

353

Chemical delivery systems and soft drugs: Retrometabolic approaches of drug design  

PubMed Central

Inclusion of metabolic considerations in the drug design process leads to significant development in the field of chemical drug targeting and the design of safer drugs during past few years which is a part of an approach now designated as Retro metabolic drug design (RMDD). This approach represents systematic methodologies that integrate structure–activity and structure–metabolism relationships and are aimed to design safe, locally active compounds with an improved therapeutic index. It embraces two distinct methods, chemical delivery systems and a soft drug approach. Present review recapitulates an impression of RMDD giving reflections on the chemical delivery system and the soft drug approach and provides a variety of examples to embody its concepts. Successful application of such design principles has already been applied to a number of marketed drugs like esmolol; loteprednol etc., and many other candidates like beta blockers, ACE inhibitors, alkylating agents, antimicrobials etc., are also under investigation. PMID:25161372

Bhardwaj, Yashumati Ratan; Pareek, Ashutosh; Jain, Vivek; Kishore, Dharma

2013-01-01

354

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

355

Polycationic nanoparticles synthesized using ARGET ATRP for drug delivery.  

PubMed

This work provides a systemic comparison for ARGET ATRP and UV-initiated polycationic nanoparticles for drug delivery and a guide to deciding which type of polycationic nanoparticles have the best properties for specific applications. Polycationic nanoparticles were synthesized using a previously developed UV-initiated photoemulsion polymerization or a newly developed ARGET ATRP synthesis technique. The effect of the ratio of hydrophobic monomer in the feed was evaluated. Increasing the feed ratio of hydrophobic monomer was necessary to maintain biocompatibility and pH-responsive membrane disruptive characteristics when switching from the UV-initiated polymerization to ARGET ATRP. The resulting polycationic nanoparticles have utility as drug delivery carriers for hydrophobic drugs and/or nucleic acids. PMID:23396094

Forbes, D C; Creixell, M; Frizzell, H; Peppas, N A

2013-08-01

356

Functionalized mesoporous silica materials for controlled drug delivery.  

PubMed

In the past decade, non-invasive and biocompatible mesoporous silica materials as efficient drug delivery systems have attracted special attention. Great progress in structure control and functionalization (magnetism and luminescence) design has been achieved for biotechnological and biomedical applications. This review highlights the most recent research progress on silica-based controlled drug delivery systems, including: (i) pure mesoporous silica sustained-release systems, (ii) magnetism and/or luminescence functionalized mesoporous silica systems which integrate targeting and tracking abilities of drug molecules, and (iii) stimuli-responsive controlled release systems which are able to respond to environmental changes, such as pH, redox potential, temperature, photoirradiation, and biomolecules. Although encouraging and potential developments have been achieved, design and mass production of novel multifunctional carriers, some practical biological application, such as biodistribution, the acute and chronic toxicities, long-term stability, circulation properties and targeting efficacy in vivo are still challenging. PMID:22441299

Yang, Piaoping; Gai, Shili; Lin, Jun

2012-05-01

357

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

358

Smart drug delivery injector microsystem based on pyrotechnical actuation  

NASA Astrophysics Data System (ADS)

A smart drug delivery injector microsystem is presented based on small pyrotechnics to impulse drugs to be injected to a human being. The proposal refers to a feasibility demonstration of the technology for pharmaceutical chips. These chips would be around some cm2 in section and will be able to inject a drug into de subject skin responding to an electrical signal. The product derived from this activity will be useful for astronaut's health, being able to administrate emergency doses of products (for instance cardio-tonic or hypoallegic drugs) enough to survive an emergency situation (as it can be a heart attack during EVA). The system can also be used for easy administration of drugs needed for physiological research. The usefulness of the device in terrestrial applications has no doubt, allowing remote administration of drugs to patients whose biomedical parameters are remotely monitored. The concept proposed here is new in combining the idea of pharmaceutical chip with the ultrasonic droplet technology and the use of pyrotechnics to provide energy to the drug to be injected. The proposed Drug Injector Microsystem is based on 2 main blocks:- Micropyrotechnic system: defines the ignition part based on pyrotechnic.- Microfluidic system: defines the drug injection part. This part is also divided in different critical parts: Expansion chamber, membrane or piston, drug reservoir and a needle. Different sensors are placed on the expansion chamber of microfluidic system and on the micropyrotechnic system. A complete electronic module is implemented with a PC interface to define flexible and user friendly experiences showing the smart drug delivery injector microsystem principle.

Puig-Vidal, Manel; Lopez, Jaime; Miribel, Pere; Samitier-Marti, Josep; Rossi, Carole; Berthold, Axel

2003-04-01

359

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

360

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

361

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

362

Graphene and graphene oxide as new nanocarriers for drug delivery applications.  

PubMed

The biomedical applications of graphene-based materials, including drug delivery, have grown rapidly in the past few years. Graphene and graphene oxide have been extensively explored as some of the most promising biomaterials for biomedical applications due to their unique properties: two-dimensional planar structure, large surface area, chemical and mechanical stability, superb conductivity and good biocompatibility. These properties result in promising applications for the design of advanced drug delivery systems and delivery of a broad range of therapeutics. In this review we present an overview of recent advances in this field of research. We briefly describe current methods for the surface modification of graphene-based nanocarriers, their biocompatibility and toxicity, followed by a summary of the most appealing examples demonstrated for the delivery of anti-cancer drugs and genes. Additionally, new drug delivery concepts based on controlling mechanisms, including targeting and stimulation with pH, chemical interactions, thermal, photo- and magnetic induction, are discussed. Finally the review is summarized, with a brief conclusion of future prospects and challenges in this field. PMID:23958782

Liu, Jingquan; Cui, Liang; Losic, Dusan

2013-12-01

363

Drug delivery to solid tumors by elastin-like polypeptides  

PubMed Central

Thermally responsive elastin-like polypeptides (ELPs) are a promising class of recombinant biopolymers for the delivery of drugs and imaging agents to solid tumors via systemic or local administration. This article reviews four applications of ELPs to drug delivery, with each delivery mechanism designed to best exploit the relationship between the characteristic transition temperature (Tt) of the ELP and body temperature (Tb). First, when Tt >> Tb, small hydrophobic drugs can be conjugated to the C-terminus of the ELP to impart the amphiphilicity needed to mediate the self-assembly of nanoparticles. These systemically delivered ELP-drug nanoparticles preferentially localize to the tumor site via the EPR effect, resulting in reduced toxicity and enhanced treatment efficacy. The remaining three approaches take direct advantage of the thermal responsiveness of ELPs. In the second strategy, where Tb < Tt < 42 °C, an ELP-drug conjugate can be injected in conjunction with external application of mild hyperthermia to the tumor to induce ELP coacervation and an increase in concentration within the tumor vasculature. The third approach utilizes hydrophilic-hydrophobic ELP block copolymers that have been designed to assemble into nanoparticles in response to hyperthermai due to the independent thermal transition of the hydrophobic block, thus resulting in multivalent ligand display of a ligand for spatially enhanced vascular targeting. In the final strategy, ELPs with Tt < Tb are conjugated with radiotherapeutics, injtect intioa tumor where they undergo coacervation to form an injectable drug depot for intratumoral delivery. These injectable coacervate ELP-radionuclide depots display a long residence in the tumor and result in inhibition of tumor growth. PMID:20546809

McDaniel, Jonathan R.; Callahan, Daniel J.; Chilkoti, Ashutosh

2010-01-01

364

Catheter systems for intrathecal drug delivery.  

PubMed

A prospective study of intrathecal catheter reliability was performed at Rush-Presbyterian-St. Luke's Medical Center. All 102 patients who had baclofen administered chronically for spasticity via an implanted drug pump were included. Sixty percent of the patients had no catheter complications; the remaining patients had one to five complications over their course of treatment. Survival analysis demonstrated a steady rate of malfunction up to 80 months, with the mean time to first failure recorded at 20 months. Kinks, holes, breaks, dislodgments, and disconnections were the most common complications. On the basis of their research the authors conclude that the thin-walled silastic catheter does not perform well and that larger, thick-walled catheters should be used. PMID:7616263

Penn, R D; York, M M; Paice, J A

1995-08-01

365

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

366

Nanoparticles: Emerging carriers for drug delivery.  

PubMed

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

2011-07-01

367

Some relationships between addiction and drug delivery to the brain.  

PubMed

Hemodynamic radioisotope studies of brain blood flow in humans have been correlated with the delivery of some common addictive drugs. Both lipophilic and hydrophilic tracers were used in the hemodynamic studies. Iodoantipyrine is lipophilic and is completely cleared by brain during a single brain circulatory passage, as are cocaine and nicotine. Iodohippurate is hydrophilic, so its brain clearance after IV injection resembles that of morphine. The earlier studies performed in humans have been related here with recent studies of blood brain penetration of drugs of abuse. As presented, these separate studies are consistent with the proposed hypothesis that the interval between drug intake and perceived effect is a significant consideration when explaining severity of addiction. The shorter the time interval between drug intake and its perceived effect, the more severe the addiction appears to be. This relationship may explain differences in severity of addiction to the same drug taken by various routes of administration. PMID:1501682

Oldendorf, W H

1992-01-01

368

Nanostructured porous Si-based nanoparticles for targeted drug delivery  

PubMed Central

One of the backbones in nanomedicine is to deliver drugs specifically to unhealthy cells. Drug nanocarriers can cross physiological barriers and access different tissues, which after proper surface biofunctionalization can enhance cell specificity for cancer therapy. Recent developments have highlighted the potential of mesoporous silica (PSiO2) and silicon (PSi) nanoparticles for targeted drug delivery. In this review, we outline and discuss the most recent advances on the applications and developments of cancer therapies by means of PSiO2 and PSi nanomaterials. Bio-engineering and fine tuning of anti-cancer drug vehicles, high flexibility and potential for sophisticated release mechanisms make these nanostructures promising candidates for “smart” cancer therapies. As a result of their physicochemical properties they can be controllably loaded with large amounts of drugs and coupled to homing molecules to facilitate active targeting. The main emphasis of this review will be on the in vitro and in vivo studies. PMID:23507894

Shahbazi, Mohammad-Ali; Herranz, Barbara; Santos, Helder A.

2012-01-01

369

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.

370

Novel Drug Delivery System Shows Early Promise for Treating Lupus in Mice  

MedlinePLUS

... Lupus in Mice A drug delivery system using nanoparticle technology that allows for better targeting of specific ... be effectively programmed to seek specific cells. Although nanoparticle drug delivery systems have been used experimentally to ...

371

Carboxymethyl starch and lecithin complex as matrix for targeted drug delivery: I. Monolithic mesalamine forms for colon delivery.  

PubMed

For drugs expected to act locally in the colon, and for successful treatment, a delivery device is necessary, in order to limit the systemic absorption which decreases effectiveness and causes important side effects. Various delayed release systems are currently commercialized; most of them based on pH-dependent release which is sensitive to gastrointestinal pH variation. This study proposes a novel excipient for colon delivery. This new preparation consists in the complexation between carboxymethyl starch (CMS) and Lecithin (L). As opposed to existing excipients, the new complex is pH-independent, inexpensive, and easy to manufacture and allows a high drug loading. FTIR, X-ray, and SEM structural analysis all support the hypothesis of the formation of a complex. By minor variation of the excipient content within the tablet, it is possible to modulate the release time and delivery at specific sites of the gastrointestinal tract. This study opens the door to a new pH-independent delivery system for mesalamine targeted administration. Our novel formulation fits well with the posology of mesalamine, used in the treatment of Inflammatory Bowel Disease (IBD), which requires repeated administrations (1g orally four times a day) to maintain a good quality of life. PMID:23562535

Mihaela Friciu, Maria; Canh Le, Tien; Ispas-Szabo, Pompilia; Mateescu, Mircea Alexandru

2013-11-01

372

Practical considerations and patient selection for intrathecal drug delivery in the management of chronic pain  

PubMed Central

Chronic pain continues to pose substantial and growing challenges for patients, caregivers, health care professionals, and health care systems. By the time a patient with severe refractory pain sees a pain specialist for evaluation and management, that patient has likely tried and failed several nonpharmacologic and pharmacologic approaches to pain treatment. Although relegated to one of the interventions of “last resort”, intrathecal drug delivery can be useful for improving pain control, optimizing patient functionality, and minimizing the use of systemic pain medications in appropriately selected patients. Due to its clinical and logistical requirements, however, intrathecal drug delivery may fit poorly into the classic pain clinic/interventional model and may be perceived as a “critical mass” intervention that is feasible only for large practices that have specialized staff and appropriate office resources. Potentially, intrathecal drug delivery may be more readily adopted into larger practices that can commit the necessary staff and resources to support patients’ needs through the trialing, initiation, monitoring, maintenance, and troubleshooting phases of this therapy. Currently, two agents – morphine and ziconotide – are approved by the United States Food and Drug Administration for long-term intrathecal delivery. The efficacy and safety profiles of morphine have been assessed in long-term, open-label, and retrospective studies of >400 patients with chronic cancer and noncancer pain types. The efficacy and safety profiles of ziconotide have been assessed in three double-blind, placebo-controlled trials of 457 patients, and safety has been assessed in 1,254 patients overall, with severe chronic cancer, noncancer, and acquired immunodeficiency syndrome pain types. Both agents are highlighted as first-line intrathecal therapy for the management of neuropathic or nociceptive pain. The purpose of this review is to discuss practical considerations for intrathecal drug delivery, delineate criteria for the identification and selection of candidates for intrathecal drug delivery, and consider which agent may be more appropriate for individual patients.

Saulino, Michael; Kim, Philip S; Shaw, Erik

2014-01-01

373

Formulation and Evaluation of Floating Drug Delivery System of Famotidine  

PubMed Central

A multiple unit oral floating drug delivery system of famotidine was developed to prolong gastric residence time, target stomach mucosa and increase drug bioavailability. Drug and polymer compatibility was studied by subjecting physical mixtures of drug and polymers to differential scanning calorimetry. Cod liver oil entrapped calcium alginate beads containing famotidine, capable of floating in the gastric condition were formulated and evaluated. The gel beads were prepared by emulsion gelation method by employing sodium alginate alone and mixture of sodium alginate and hydrophilic copolymers such as carbopol 934P and hydroxypropylmethylcellulose K15M grade in three different ratios. The effect of selected factors, such as percentage of oil and amount of copolymers on floating properties was investigated. The beads were evaluated for percent drug loading, drug entrapment efficiency, buoyancy and in vitro drug release. The in vitro drug release study of the beads was carried out in simulated gastric media employing a modified Rosette-Rice test apparatus. Wherein, the apparatus was further modified by incorporating a water jacket to the apparatus to circulate hot water to maintain 37±2° for throughout the release study. All the oil entrapped calcium alginate beads floated if a sufficient amount of oil was used. Beads formulated employing sodium alginate alone could not sustain the drug release up to 8 h, whereas beads formulated with mixture of sodium alginate and copolymers demonstrated sustained release of famotidine up to 8 h. The results suggested that cod liver oil entrapped calcium alginate beads were promising as a carrier for intragastric floating drug delivery of famotidine. PMID:21969746

Satishbabu, B. K.; Sandeep, V. R.; Ravi, R. B.; Shrutinag, R.

2010-01-01

374

Synthetic Polymers as Drug-Delivery Vehicles in Medicine  

PubMed Central

Cancerous diseases present a formidable health problem worldwide. While the chemotherapy of cancer, in conjunction with other treatment modalities, has reached a significant level of maturity, efficacious use of such agents is still restricted by numerous pharmacological deficiencies, such as poor water solubility, short serum circulation lifetimes, and low bioavailability resulting from lack of affinity to cancer tissue and inadequate mechanisms of cell entry. More critically still, most drugs suffer from toxic side effects and a risk of drug resistance. The class of platinum anticancer drugs, although outstandingly potent, is particularly notorious in that respect. Among the countless methods developed in recent years in an effort to overcome these deficiencies, the technology of polymer-drug conjugation stands out as a particularly advanced treatment modality. The strategy involves the bioreversible binding, conjugating, of a medicinal agent to a water-soluble macromolecular carrier. Following pharmacokinetic pathways distinctly different from those of the common, nonpolymeric drugs, the conjugate so obtained will act as a prodrug providing safe transport of the bioactive agent to and into the affected, that is, cancerous cell for its ultimate cell-killing activity. The present treatise will acquaint us with the pharmacological fundamentals of this drug delivery approach, applied here specifically to the metalorganic platinum-type drug systems and the organometallic ferrocene drug model. We will see just how this technology leads to conjugates distinctly superior in antiproliferative activity to cisplatin, a clinically used antitumor agent used here as a standard. Polymer-drug conjugation involving metal-based and other medicinal agents has unquestionably matured to a practical tool to the pharmaceutical scientist, and all indications point to an illustrious career for this nascent drug delivery approach in the fight against cancer and other human maladies. PMID:18497867

Neuse, Eberhard W.

2008-01-01

375

Formulation and evaluation of floating drug delivery system of famotidine.  

PubMed

A multiple unit oral floating drug delivery system of famotidine was developed to prolong gastric residence time, target stomach mucosa and increase drug bioavailability. Drug and polymer compatibility was studied by subjecting physical mixtures of drug and polymers to differential scanning calorimetry. Cod liver oil entrapped calcium alginate beads containing famotidine, capable of floating in the gastric condition were formulated and evaluated. The gel beads were prepared by emulsion gelation method by employing sodium alginate alone and mixture of sodium alginate and hydrophilic copolymers such as carbopol 934P and hydroxypropylmethylcellulose K15M grade in three different ratios. The effect of selected factors, such as percentage of oil and amount of copolymers on floating properties was investigated. The beads were evaluated for percent drug loading, drug entrapment efficiency, buoyancy and in vitro drug release. The in vitro drug release study of the beads was carried out in simulated gastric media employing a modified Rosette-Rice test apparatus. Wherein, the apparatus was further modified by incorporating a water jacket to the apparatus to circulate hot water to maintain 37±2° for throughout the release study. All the oil entrapped calcium alginate beads floated if a sufficient amount of oil was used. Beads formulated employing sodium alginate alone could not sustain the drug release up to 8 h, whereas beads formulated with mixture of sodium alginate and copolymers demonstrated sustained release of famotidine up to 8 h. The results suggested that cod liver oil entrapped calcium alginate beads were promising as a carrier for intragastric floating drug delivery of famotidine. PMID:21969746

Satishbabu, B K; Sandeep, V R; Ravi, R B; Shrutinag, R

2010-11-01

376

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

377

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

E-print Network

with transdermal drug release modeling, be used to control drug release. Diffusion, water- anotherAdvanced 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

Peppas, Nicholas A.

378

Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute  

Microsoft Academic Search

Transdermal drug delivery systems (TDDS), also known as “patches,” are dosage forms designed to deliver a therapeutically effective amount of drug across a patient’s skin. The adhesive of the transdermal drug delivery system is critical to the safety, efficacy and quality of the product. In the Drug Quality Reporting System (DQRS), the United States Food and Drug Administration (FDA) has

Anna M. Wokovich; Suneela Prodduturi; William H. Doub; Ajaz S. Hussain; Lucinda F. Buhse

2006-01-01

379

Mesenchymal stem cells for anti-cancer drug delivery.  

PubMed

Self renewal, extensive proliferation and multilineage differentiation ability in vitro and in vivo make mesenchymal stem cells (MSCs) powerful tools for tissue engineering. Beyond their potential uses in regenerative medicine, an emerging field of research aims to utilize MSCs for anti-cancer treatment. These strategies are based on the remarkable ability of MSCs to localize and integrate into tumor stroma and deliver anti-cancer agents (US20100055167, US20120207725, US20120010499). Genetically engineered MSCs can specifically target different tumor types and locally secrete therapeutic proteins such as interferons ? and ?, interleukins 2 and 12 or chemokine CX3CL1 (US20110027239, US20120087901, WO2012071527). In addition, MSCs have also been engineered to deliver oncolytic viruses, for targeted chemotherapy using enzyme prodrug conversion or for inducing tumor cell apoptosis by delivering tumor necrosis factor-related apoptosis inducing ligand (TRAIL) (WO2012106281). The patent databases FPO and Delphion were used to locate patents that were published between 2005 and 2013. Here, we present the current progress and the most recent patents on MSC anti-cancer drug delivery systems and discuss future directions in the field. PMID:23688246

Gjorgieva, Darinka; Zaidman, Nathan; Bosnakovski, Darko

2013-09-01

380

Amphiphilic polysaccharide-hydrophobicized graft polymeric micelles for drug delivery nanosystems.  

PubMed

Self-assembled amphiphilic graft copolymers in aqueous solution to form polymeric micelles, have received growing scientific attention over the years. Among the polymeric micelles, hydrophobicized polysaccharides have currently become one of the hottest researches in the field of drug delivery nanosystems. It is attributable to such appealing properties as small particle size and narrow size distribution, distinctive core-shell structure, high solubilization capacity and structural stability, tumor passive localization by enhanced permeability and retention (EPR) effect, active targeting ability via tailored targeting promoiety, long-circulation property and facile preparation. The polymeric micelles self-assembled by hydrophobicized polysaccharides can be employed as targeted drug delivery nanosystem by including thermo- or pH-sensitive components or by attaching specific targeted moieties to the outer hydrophilic surface. Beside encapsulation of water-insoluble drugs, hydrophobicized polysaccharide polymeric micelles can complex with charged proteins or peptide drugs through electrostatic force or hydrogen bond, and serve as an effective non-viral vector for gene delivery. In the latter case, polymeric micelles can not only markedly protect these macromolecules from degradation by protease or ribozymes, but also increase the gene transfection efficiency. This review will highlight the state of the art self-assembled mechanism, characterization, preparation methods and surface modification of hydrophobicized polysaccharide polymeric micelles and their recent rapid applications as drug delivery nanosystems. PMID:21568897

Liu, Y; Sun, J; Zhang, P; He, Z

2011-01-01

381

Microneedle: a Effective and Safe Tool for Drug Delivery  

Microsoft Academic Search

Microneedle-based vaccination with the current anthrax vaccine produced an equally effective immune response to intramuscular injection in rabbits using smaller dosage say researcher from Maryland and North Carolina. In the study researchers compared the efficacy of immunizing rabbits with the current anthrax vaccine intradermally using a microneedle and intramuscularly using a conventional needle. Results showed that intradermal delivery required less

Pandey Shivanand; Patel Binal; R. Mahalaxmi; Devmurari Viral; N. P. Jivani

382

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

383

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

384

Microneedles array with biodegradable tips for transdermal drug delivery  

NASA Astrophysics Data System (ADS)

The paper presented an enhancement solution for transdermal drug delivery using microneedles array with biodegradable tips. The microneedles array was fabricated by using deep reactive ion etching (DRIE) and the biodegradable tips were made to be porous by electrochemical etching process. The porous silicon microneedle tips can greatly enhance the transdermal drug delivery in a minimum invasion, painless, and convenient manner, at the same time; they are breakable and biodegradable. Basically, the main problem of the silicon microneedles consists of broken microneedles tips during the insertion. The solution proposed is to fabricate the microneedle tip from a biodegradable material - porous silicon. The silicon microneedles are fabricated using DRIE notching effect of reflected charges on mask. The process overcomes the difficulty in the undercut control of the tips during the classical isotropic silicon etching process. When the silicon tips were formed, the porous tips were then generated using a classical electrochemical anodization process in MeCN/HF/H2O solution. The paper presents the experimental results of in vitro release of calcein and BSA with animal skins using a microneedle array with biodegradable tips. Compared to the transdermal drug delivery without any enhancer, the microneedle array had presented significant enhancement of drug release.

Iliescu, Ciprian; Chen, Bangtao; Wei, Jiashen; Tay, Francis E. H.

2008-12-01

385

A Novel Multilayered Multidisk Oral Tablet for Chronotherapeutic Drug Delivery  

PubMed Central

A Multilayered Multidisk Tablet (MLMDT) comprising two drug-loaded disks enveloped by three drug-free barrier layers was developed for use in chronotherapeutic disorders, employing two model drugs, theophylline and diltiazem HCl. The MLMDT was designed to achieve two pulses of drug release separated by a lag phase. The polymer disk comprised hydroxyethylcellulose (HEC) and ethylcellulose (EC) granulated using an aqueous dispersion of EC. The polymeric barrier layers constituted a combination of pectin/Avicel (PBL) (1st barrier layer) and hydroxypropylmethylcellulose (HPMC) (HBL1 and HBL2) as the 2nd and 3rd barrier layers, respectively. Sodium bicarbonate was incorporated into the diltiazem-containing formulation for delayed drug release. Erosion and swelling studies confirmed the manner in which the drug was released with theophylline formulations exhibiting a maximum swelling of 97% and diltiazem containing formulations with a maximum swelling of 119%. FTIR spectra displayed no interactions between drugs and polymers. Molecular mechanics simulations were undertaken to predict the possible orientation of the polymer morphologies most likely affecting the MLMDT performance. The MLMDT provided two pulses of drug release, separated by a lag phase, and additionally it displayed desirable friability, hardness, and uniformity of mass indicating a stable formulation that may be a desirable candidate for chronotherapeutic drug delivery. PMID:24024200

Khan, Zaheeda; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Pillay, Viness

2013-01-01

386

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

387

Nanoparticle Delivery of Anti-Tuberculosis Chemotherapy as a Potential Mediator Against Drug-Resistant Tuberculosis  

PubMed Central

Drug-resistant tuberculosis is quickly emerging as one of the largest threats to the global health community. Current chemotherapy for tuberculosis dates back to the 1950s and is arduous, lengthy, and remains extremely difficult to complete in many of the highest burdened areas. This causes inadequate or incomplete treatment, resulting in genetic selection of drug-resistant strains. With a dearth of novel anti-TB drug candidates in the development pipeline, nanoparticle technology allows us to take current chemotherapies and deliver them more efficaciously, reducing the frequency and duration of treatment and increasing bioavailability. This approach can improve patient adherence, reduce pill burden, and shorten time to completion, all which are at the heart of drug resistance. This review examines the multiple advantages of nanoparticle drug delivery of tuberculosis chemotherapy and summarizes the challenges in implementation. PMID:22180674

Smith, Jonathan Paul

2011-01-01

388

A data-driven predictive approach for drug delivery using machine learning techniques.  

PubMed

In drug delivery, there is often a trade-off between effective killing of the pathogen, and harmful side effects associated with the treatment. Due to the difficulty in testing every dosing scenario experimentally, a computational approach will be helpful to assist with the prediction of effective drug delivery methods. In this paper, we have developed a data-driven predictive system, using machine learning techniques, to determine, in silico, the effectiveness of drug dosing. The system framework is scalable, autonomous, robust, and has the ability to predict the effectiveness of the current drug treatment and the subsequent drug-pathogen dynamics. The system consists of a dynamic model incorporating both the drug concentration and pathogen population into distinct states. These states are then analyzed using a temporal model to describe the drug-cell interactions over time. The dynamic drug-cell interactions are learned in an adaptive fashion and used to make sequential predictions on the effectiveness of the dosing strategy. Incorporated into the system is the ability to adjust the sensitivity and specificity of the learned models based on a threshold level determined by the operator for the specific application. As a proof-of-concept, the system was validated experimentally using the pathogen Giardia lamblia and the drug metronidazole in vitro. PMID:22384063

Li, Yuanyuan; Lenaghan, Scott C; Zhang, Mingjun

2012-01-01

389

A Data-Driven Predictive Approach for Drug Delivery Using Machine Learning Techniques  

PubMed Central

In drug delivery, there is often a trade-off between effective killing of the pathogen, and harmful side effects associated with the treatment. Due to the difficulty in testing every dosing scenario experimentally, a computational approach will be helpful to assist with the prediction of effective drug delivery methods. In this paper, we have developed a data-driven predictive system, using machine learning techniques, to determine, in silico, the effectiveness of drug dosing. The system framework is scalable, autonomous, robust, and has the ability to predict the effectiveness of the current drug treatment and the subsequent drug-pathogen dynamics. The system consists of a dynamic model incorporating both the drug concentration and pathogen population into distinct states. These states are then analyzed using a temporal model to describe the drug-cell interactions over time. The dynamic drug-cell interactions are learned in an adaptive fashion and used to make sequential predictions on the effectiveness of the dosing strategy. Incorporated into the system is the ability to adjust the sensitivity and specificity of the learned models based on a threshold level determined by the operator for the specific application. As a proof-of-concept, the system was validated experimentally using the pathogen Giardia lamblia and the drug metronidazole in vitro. PMID:22384063

Zhang, Mingjun

2012-01-01

390

Generic leak-free drug storage and delivery for microneedle-based systems  

Microsoft Academic Search

We present a generic liquid packaging method for micro-machined drug delivery systems with microneedles. Hollow microneedles are sealed with thin gold membranes at the openings on the needle tip on wafer level. This provides both a seal and an evaporation barrier to the drug delivery system on chip level. In addition, the membranes may also prevent drug delivery through needles

N. Roxhed; P. Griss; G. Stemme

2005-01-01

391

Application of In Situ Polymerization for Design and Development of Oral Drug Delivery Systems  

Microsoft Academic Search

Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to\\u000a light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides

Ndidi Ngwuluka; Joseph Reo; Linda Felton; Stephen Howard

2010-01-01

392

A thermal microjet system with tapered micronozzles fabricated by inclined UV lithography for transdermal drug delivery  

E-print Network

for transdermal drug delivery This article has been downloaded from IOPscience. Please scroll down to see the full/025014 Abstract Transdermal drug delivery can be enabled by various methods that increase the permeability. This thermal microjet system can serve as a tool not only for transdermal drug delivery, but also for a variety

393

Local controlled drug delivery to the brain: mathematical modeling of the underlying mass transport mechanisms.  

PubMed

The mass transport mechanisms involved in the controlled delivery of drugs to living brain tissue are complex and yet not fully understood. Often the drug is embedded within a polymeric or lipidic matrix, which is directly administered into the brain tissue, that is, intracranially. Different types of systems, including microparticles and disc- or rod-shaped implants are used to control the release rate and, thus, to optimize the drug concentrations at the site of action in the brain over prolonged periods of time. Most of these dosage forms are biodegradable to avoid the need for the removal of empty remnants after drug exhaustion. Various physical and chemical processes are involved in the control of drug release from these systems, including water penetration, drug dissolution, degradation of the matrix and drug diffusion. Once the drug has been released from the delivery system, it has to be transported through the living brain tissue to the target site(s). Again, a variety of phenomena, including diffusion, drug metabolism and degradation, passive or active uptake into CNS tissue and convection can be of importance for the fate of the drug. An overview is given of the current knowledge of the nature of barriers to free access of drug to tumour sites within the brain and the state of the art of: (i) mathematical modeling approaches describing the physical transport processes and chemical reactions which can occur in different types of intracranially administered drug delivery systems, and of (ii) theories quantifying the mass transport phenomena occurring after drug release in the living tissue. Both, simplified as well as complex mathematical models are presented and their major advantages and shortcomings discussed. Interestingly, there is a significant lack of mechanistically realistic, comprehensive theories describing both parts in detail, namely, drug transport in the dosage form and in the living brain tissue. High quality experimental data on drug concentrations in the brain tissue are difficult to obtain, hence this is itself an issue in testing mathematical approaches. As a future perspective, the potential benefits and limitations of these mathematical theories aiming to facilitate the design of advanced intracranial drug delivery systems and to improve the efficiency of the respective pharmacotherapies are discussed. PMID:16647231

Siepmann, J; Siepmann, F; Florence, A T

2006-05-18

394

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

395

Fundamental study for development magnetic drug delivery system  

NASA Astrophysics Data System (ADS)

Side-effects and lowering effects by diffusion of drugs such as anticancer agents is one of the serious issues in medication. To solve this problem, it is necessary to control the drugs quantitatively, spatially and temporally within the human body. Magnetic drug delivery system (MDDS) is one of the technologies to make it possible, in which the ferromagnetic drug injected into the blood vessel is conducted to diseased part by external magnetic force. As a fundamental experiment, the accumulation experiment using ferromagnetic particles were performed with simulated capillary vessels composed of glass beads channels in this work. Additionally, accumulation calculation of ferromagnetic particles was conducted to check the validity of accumulation experiment. From these result, the 2D distribution of particle accumulation in the experiment corresponded with that of particle accumulation in the calculation. It was suggested that the proper position of magnet should be changed according to the depth of diseased part.

Hirota, Y.; Akiyama, Y.; Izumi, Y.; Nishijima, S.

2009-10-01

396

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

397

Graphene-based nanomaterials for drug delivery and tissue engineering.  

PubMed

Nanomaterials offer interesting physicochemical and biological properties for biomedical applications due to their small size, large surface area and ability to interface/interact with the cells/tissues. Graphene-based nanomaterials are fast emerging as "two-dimensional wonder materials" due to their unique structure and excellent mechanical, optical and electrical properties and have been exploited in electronics and other fields. Emerging trends show that their exceptional properties can be exploited for biomedical applications, especially in drug delivery and tissue engineering. This article presents a comprehensive review of various types and properties of graphene family nanomaterials. We further highlight how these properties are being exploited for drug delivery and tissue engineering applications. PMID:24161530

Goenka, Sumit; Sant, Vinayak; Sant, Shilpa

2014-01-10

398

Magnetic Nanoparticles in MR Imaging and Drug Delivery  

PubMed Central

Magnetic nanoparticles (MNPs) possess unique magnetic properties and the ability to function at the cellular and molecular level of biological interactions making them an attractive platform as contrast agents for magnetic resonance imaging (MRI) and as carriers for drug delivery. Recent advances in nanotechnology have improved the ability to specifically tailor the features and properties of MNPs for these biomedical applications. To better address specific clinical needs, MNPs with higher magnetic moments, non-fouling surfaces, and increased functionalities are now being developed for applications in the detection, diagnosis, and treatment of malignant tumors, cardiovascular disease, and neurological disease. Through the incorporation of highly specific targeting agents and other functional ligands, such as fluorophores and permeation enhancers, the applicability and efficacy of these MNPs have greatly increased. This review provides a background on applications of MNPs as MR imaging contrast agents and as carriers for drug delivery and an overview of the recent developments in this area of research. PMID:18558452

Sun, Conroy; Lee, Jerry S.H.; Zhang, Miqin

2009-01-01

399

Magnetic nanoparticles for multi-imaging and drug delivery.  

PubMed

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

2013-04-01

400

Spermbots: potential impact for drug delivery and assisted reproductive technologies.  

PubMed

Micromotors and nanomotors are an emerging research field that aims at achieving locomotion on the microscale for a variety of applications such as drug delivery, single cell manipulation, microsensors and lab-on-a-chip devices, just to point out a few. The enthusiastic development of hybrid micromotors harnessing biological power sources for physiologically compatible nano/microdevices has recently brought a lot of attention to the international research community that is looking for a solution for the actuation and locomotion on the microscale. This article describes the potential of sperm-driven micro-bio-robots in the biomedical field such as drug delivery or single cell manipulation. Herein, a specific potential of the sperm-driven micro-bio-robot is described that might have impact on the development of assisted reproductive technologies. PMID:24882224

Magdanz, Veronika; Schmidt, Oliver G

2014-08-01

401

Polymerized rosin: novel film forming polymer for drug delivery.  

PubMed

Polymerized rosin (PR) a novel film forming polymer is characterized and investigated in the present study for its application in drug delivery. Films were produced by a casting/solvent evaporation method from plasticizer free and plasticizer containing solutions. Films prepared from different formulations were studied for their mechanical (tensile strength, percent elongation and Young's modulus), water vapour transmission and moisture absorption characteristics. Neat PR films were slightly brittle and posed the problem of breaking during handling. Hydrophobic plasticizers, dibutyl sebacate and tributyl citrate, improved the mechanical properties of free films with both the plasticizers showing significant effects on film elongation. Release of diclofenac sodium (model drug) from coated pellets was sustained with high coating levels. Concentration of plasticizer was found to affect the release profile. PR films plasticized with hydrophobic plasticizers could therefore be used in coating processes for the design of oral sustained delivery dosage forms. PMID:12433446

Fulzele, S V; Satturwar, P M; Dorle, A K

2002-12-01

402

Advances in self-assembled chitosan nanomaterials for drug delivery.  

PubMed

Nanomaterials based on chitosan have emerged as promising carriers of therapeutic agents for drug delivery due to good biocompatibility, biodegradability, and low toxicity. Chitosan originated nanocarriers have been prepared by mini-emulsion, chemical or ionic gelation, coacervation/precipitation, and spray-drying methods. As alternatives to these traditional fabrication methods, self-assembled chitosan nanomaterials show significant advantages and have received growing scientific attention in recent years. Self-assembly is a spontaneous process by which organized structures with particular functions and properties could be obtained without additional complicated processing or modification steps. In this review, we focus on recent progress in the design, fabrication and physicochemical aspects of chitosan-based self-assembled nanomaterials. Their applications in drug delivery of different therapeutic agents are also discussed in details. PMID:25109677

Yang, Yu; Wang, Shengpeng; Wang, Yitao; Wang, Xiaohui; Wang, Qun; Chen, Meiwan

2014-11-15

403

Non-destructively shattered mesoporous silica for protein drug delivery  

PubMed Central

Mesoporous silicas have been extensively used for entrapping small chemical molecules and biomacromolecules for drug delivery. We hypothesize that the loading density of biomacromlecules such as proteins in mesoporous silicas could be limited due to disordering in the pore structure and long diffusion time in the pore channels. We shattered mesoporous silicas non-destructively resulting in improved intramesoporous structures and reduced particle sizes in aqueous solutions by a powerful sonication, where the mesoporous structures were still well maintained. The sonication-shattered mesoporous silica can increase the protein loading density to nearly 2.7 times as high as that of the non-shattered one, demonstrating that significantly more mesopore space of the silica could be accessible by the protein molecules, which may result in more sustained protein drug delivery. PMID:23687455

Lei, Chenghong; Chen, Baowei; Li, Xiaolin; Qi, Wen; Liu, Jun

2013-01-01

404

THE USE OF NANOPARTICLE-MEDIATED TARGETED GENE SILENCING AND DRUG DELIVERY TO OVERCOME TUMOR DRUG RESISTANCE  

PubMed Central

Overexpression of drug efflux transporters such as P-glycoprotein (P-gp) enables cancer cells to develop resistance to multiple anticancer drugs. Functional inhibitors of P-gp have shown promising efficacy in early clinical trials, but their long-term safety is yet to be established. A novel approach to overcome drug resistance is to use siRNA-mediated RNA interference to silence the expression of the efflux transporter. Because P-gp plays an important role in the physiological regulation of endogenous and xenobiotic compounds in the body, it is important to deliver P-gp targeted siRNA and anticancer drug specifically to tumor cells. Further, for optimal synergy, both the drug and siRNA may need to be temporally colocalized in the tumor cells. In the current study, we investigated the effectiveness of simultaneous and targeted delivery of anticancer drug, paclitaxel, along with P-gp targeted siRNA, using poly(D,L-lactide-co-glycolide) nanoparticles to overcome tumor drug resistance. Nanoparticles were surface functionalized with biotin for active tumor targeting. Dual agent nanoparticles encapsulating the combination of paclitaxel and P-gp targeted siRNA showed significantly higher cytotoxicity in vitro than nanoparticles loaded with paclitaxel alone. Enhanced therapeutic efficacy of dual agent nanoparticles could be correlated with effective silencing of the MDR1 gene that encodes for P-gp and with increased accumulation of paclitaxel in drug-resistant tumor cells. In vivo studies in a mouse model of drug-resistant tumor demonstrated significantly greater inhibition of tumor growth following treatment with biotin-functionalized nanoparticles encapsulating both paclitaxel and P-gp targeted siRNA at a paclitaxel dose that was ineffective in the absence of gene silencing. These results suggest that that the combination of P-gp gene silencing and cytotoxic drug delivery using targeted nanoparticles can overcome tumor drug resistance. PMID:19800114

Patil, Yogesh; Swaminathan, Suresh; Sadhukha, Tanmoy; Ma, Linan; Panyam, Jayanth

2009-01-01

405

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

406

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

407

Localized drugs delivery hydroxyapatite microspheres for osteoporosis therapy  

NASA Astrophysics Data System (ADS)

This study describes the preparation of hydroxyapatite microspheres for local drugs delivery. The formation of the hydroxyapatite microspheres was initiated by enzymatic decomposition of urea and accomplished by emulsification process (water-in-oil). The microspheres obtained were sintered at 500°C. Scanning electron microscope (SEM) indicated that the microspheres have various porous with random size, which maximizes the surface area. Cytotoxicity was not observed after sintering. Osteoporosis drugs, alendronate and BMP-2, were loaded into HAp microspheres and the releases of both molecules showed sustained releasing profiles.

Lee, J. H.; Ko, I. H.; Jeon, S.-H.; Chae, J. H.; Lee, E. J.; Chang, J. H.

2011-10-01

408

An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles  

PubMed Central

Background Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin. Methodology/Principal Findings Apotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano) have diameters of 25–50 ?m, which increase to 60–80 ?m upon direct loading of drug (direct-nano), and showed further increase in