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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 deliverysystems 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 drugdeliverysystems 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 drugdeliverysystems 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.
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 drugdelivery 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 drugdeliverysystems (buccal, nasal, ocular, gastro, vaginal, and rectal).
Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.
Two drugdeliverysystems have been developed from pectin recently in our laboratory. (I) Pectin gel formulations for controlled fragrance release and (II) pectin/zein hydrogels for oral drugdelivery. By altering the molecular characteristics or modifying the pectin hydrogel networks, the release ...
Colon targeted drugdeliverysystems have the potential to deliver drugs for the treatment of a variety of colonic diseases and to deliver proteins and peptides to the colon for their systemic absorption. In recent years, various pharmaceutical approaches have been developed for targeting the drugs to the colon include, formation of prodrugs, coating of pH-sensitive polymers, use of colon
Nanoparticles hold tremendous potential as an effective drugdeliverysystem. In this review we discussed recent developments in nanotechnology for drugdelivery. To overcome the problems of gene and drugdelivery, 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 drugdelivery
Interest in pain management is growing, with the emerging demand by our patients and colleagues, for pain relief. To meet\\u000a that need, pharmaceutical and medical technology companies have provided the medical field with a variety of choices and options\\u000a to deliver medication for pain control. Examination and review of the present systemic options are introduced. A more detailed\\u000a look at
A microfabricated, fully integrated drugdeliverysystem capable of secreting controlled dosages of multiple drugs over long periods of time (up to a year). The device includes a long and narrow shaped implant with a sharp leading edge for implantation under the skin of a human in a manner analogous to a sliver. The implant includes: 1) one or more micromachined, integrated, zero power, high and constant pressure generating osmotic engine; 2) low power addressable one-shot shape memory polymer (SMP) valves for switching on the osmotic engine, and for opening drug outlet ports; 3) microfabricated polymer pistons for isolating the pressure source from drug-filled microchannels; 4) multiple drug/multiple dosage capacity, and 5) anisotropically-etched, atomically-sharp silicon leading edge for penetrating the skin during implantation. The device includes an externally mounted controller for controlling on-board electronics which activates the SMP microvalves, etc. of the implant.
Krulevitch, Peter A. (Pleasanton, CA); Wang, Amy W. (Oakland, CA)
Oral mucosal drugdelivery is an alternative method of systemicdrugdelivery that offers several advantages over both injectable and enteral methods and also enhances drug bioavailability because the mucosal surfaces are usually rich in blood supply, providing the means for rapid drug transport to the systemic circulation and avoiding, in most cases, degradation by first-pass hepatic metabolism. The systems
N. V. Satheesh Madhav; Ashok K. Shakya; Pragati Shakya; Kuldeep Singh
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 deliverysystems 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
The treatment of brain disorders is particularly challenging due to the presence of a variety of formidable obstacles to deliver drugs selectively and effectively to the brain. Blood-brain-barrier (BBB) constitutes the major obstacle to the uptake of drugs into the brain following systemic administration. Intranasal delivery offers a non-invasive and convenient method to bypass the BBB and delivery of therapeutics directly to the brain. The review discusses the potential of intranasal route to deliver drugs to the brain, the mechanisms and pathways of direct nose to brain drug transport, the various factors influencing transnasal drug absorption, the conventional and novel intranasal drugdeliverysystems, the various intranasal drugdelivery techniques and devices, and examples of brain drug transport that have been feasible in treating various brain disorders. Moreover, products on the market, investigational drugs, and the author's perceptions about the prospect of intranasal delivery for treating brain disorders are also been discussed. PMID:23016642
Pharmaceutical and biotechnological research sorts protein drugdeliverysystems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drugdelivery. They also have developed hydrogels and transdermal drugdeliverysystems for peptidal drugdelivery. A receptor-mediated deliverysystem is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drugdelivery, with special emphasis on insulin delivery. PMID:23662604
Facilitated/modulated drug-deliverysystems 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-deliverysystems 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-deliverysystems 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.
Restenosis, an arterial reobstruction occurring in thirty to fifty percent of patients undergoing coronary angioplasty, because of its localized nature can possibly be best treated by local drug therapy. In recent years, several local drugdelivery strategies have been investigated for the prevention of restenosis. In this review we discuss the therapeutic potential of nanoparticles as a drugdeliverysystem
Implantable devices are currently used regularly for chronic pain relief, cardiac pacemakers, arterial infusion for cancer and insulin delivery. A MEMS based implantable drugdeliverysystem (IDDS) integrating a subcutaneous reservoir, an in plane silicon pump and associated circuitry for local or centralized delivery of therapeutic agents for chemotherapy is proposed. System configurations, flow rate analysis and applications are presented.
Smitha M. N. Rao; Amit Mhatre; Dan O. Popa; C. Chiao; Jeongsik Sin; Harry E. Stephanou
In the past, drugs were frequently administered orally, as liquids or in powder forms. To avoid problems incurred through the utilization of the oral route of drug administration, new dosage forms containing the drug(s) were introduced. As time progressed, there was a need for deliverysystems that could maintain a steady release of drug to the specific site of action.
The knowledge of the potential use of the spray-drying technology to prepare microparticulate drugdeliverysystems—microspheres and microcapsules—has been strongly improved over the last years. Various microparticulate spray drying systems used as vehicles for drug encapsulation and delivery that have been investigated for different purposes are presented here, including spray-dried powders formulated with hydrophilic polymers allowing controlled drug release, biodegradable
Eye-drops are the conventional dosage forms that account for 90% of currently accessible ophthalmic formulations. Despite the excellent acceptance by patients, one of the major problems encountered is rapid precorneal drug loss. To improve ocular drug bioavailability, there is a significant effort directed towards new drugdeliverysystems for ophthalmic administration.This chapter will focus on three representative areas of ophthalmic
Chrystèle Le Bourlais; Liliane Acar; Hosein Zia; Pierre A. Sado; Thomas Needham; Roger Leverge
To increase the therapeutic effectiveness of device-directed drugdeliverysystems for diseased cardiovascular tissues and cancerous tissues, new devices and new functional biomaterials were devised to meet the requirements as listed below: drug-infusible balloon catheter, drug-releasable and covered stents, and in situ hydrogelation on and in cancerous tissues. New therapeutic strategies based on these devices were discussed.
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 drugdelivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drugdelivery 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 drugdelivery. 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 drugdeliverysystems.
Transdermal drugdelivery represents one of the most rapidly advancing areas of novel drugdelivery. Although the concept of transdermal drugdelivery has been known since 1924, it took until 1979, as FDA approved the transdermal delivery of scopolamine, that transdermal deliverysystems [TDDS] received broad attention as novel tool for controlled release. These drugdeliverysystems are designed for controlled release of drug through the skin into systemic circulation maintaining consistent efficacy and reducing dose of the drug and its related side effects. More than 200 patents have been granted by the United State patent alone, of which more than 35 TDD products have now been approved for sale in the US, and approximately 16 active ingredients have been approved for use globally. Statistics reveal a market of $ 12.7 billion in the year 2005 which is expected to increase by $ 21.5 billion in the year 2010 and $ 31.5 billion in the year 2015. Almost all major and minor pharmaceutical companies are developing TDDS. There is not a single review article which describes patents on different types of TDDS. Thus this review is designed for patents on the different type of TDDS which would be helpful for the researcher in the field of TDDS. PMID:19519574
Samad, Abdus; Ullah, Zabih; Alam, Mohammad I; Wais, Mohd; Shams, Mohammad Shabaz
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 drugdeliverysystems 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 deliverysystems namely- oral, nasal, ophthalmic and parenteral. Ion- exchange resins have been used for the development of novel drugdeliverysystems (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 deliverysystems and as inotophoretically assisted transdermal drugdeliverysystems. 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
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 drugdeliverysystems 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 deliverysystems namely- oral, nasal, ophthalmic and parenteral. Ion- exchange resins have been used for the development of novel drugdeliverysystems (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 deliverysystems and as inotophoretically assisted transdermal drugdeliverysystems. 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
Hypertension is a chronic disease with one of the highest chances of causing death, and long-term treatment is required. The antihypertensive drugs used in the treatment are generally administered orally. The limitations of the oral route make transdermal delivery of drugs more attractive. The transdermal route offers numerous advantages including avoidance of systemic first-pass metabolism and high patient compliance. The transdermal therapeutic systems, popularly known as 'patches', deliver drugs across the skin with a constant release rate. However, skin is a unique membrane having excellent barrier properties. Either chemical enhancers or physical methods such as iontophoresis and electroporation have been used to provide effective plasma drug concentrations. This review article focuses on the approaches to enhance skin permeability of antihypertensive drugs for the optimization of transdermal therapeutic systems of these drugs and the research studies intended for the optimization of transdermal dosage forms of antihypertensive drugs are summarized. PMID:23035594
Drugs are most often administered by the oral route. However, more than 40% of new chemical entities exhibit poor aqueous solubility, resulting in unsatisfactory oral drugdelivery. Recently, much attention has been focused on self- emulsifying drugdeliverysystems (SEDDS) to improve the oral bioavailability of poorly aqueous soluble drugs. SEDDS are isotropic mixtures of oil, surfactants, solvents and co-solvents\\/surfactants.
Systemic and local delivery on the photosensitive drug Photofrin polyporphyrin was investigated in normal porcine arteries (n = 192). A macroporous balloon and a novel needle injection catheter were used for local drugdelivery and compared with systemicdelivery. Fluorescence microscopy combined with digital image analysis was used to quantify the drug-related fluorescence. Systemicdelivery showed a maximum in the
Peter Gonschior; Clemens Pahl; Tanya Y. Huehns; Florian Gerheuser; Aysel Erdemci; Katharina Larisch; Marc Dellian; Stefan Deil; Alwin-E. Goetz; Hans A. Lehr; Berthold Höfling
In the recent years, there is a growing interest in the lipid-based formulations for delivery of lipophilic drugs. Due to their potential as therapeutic agents, preferably these lipid soluble drugs are incorporated into inert lipid carriers such as oils, surfactant dispersions, emulsions, liposomes etc. Among them, emulsion forming drugdeliverysystems appear to be a unique and industrially feasible approach to overcome the problem of low oral bioavailability associated with the BCS class II drugs. Self-emulsifying formulations are ideally isotropic mixtures of oils, surfactants and co-solvents that emulsify to form fine oil in water emulsions when introduced in aqueous media. Fine oil droplets would pass rapidly from stomach and promote wide distribution of drug throughout the GI tract, thereby overcome the slow dissolution step typically observed with solid dosage forms. Recent advances in drug carrier technologies have promulgated the development of novel drug carriers such as control release self-emulsifying pellets, microspheres, tablets, capsules etc. that have boosted the use of "self-emulsification" in drugdelivery. This article reviews the different types of formulations and excipients used in emulsion forming drugdeliverysystem to enhance the bioavailability of lipophilic drugs. PMID:22568032
The purpose of writing this review on floating drugdeliverysystems (FDDS) was to compile the recent literature with special\\u000a focus on the principal mechanism of floatation to achieve gastric retention. The recent developments of FDDS including the\\u000a physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating\\u000a systems, and their classification and formulation aspects are
Implantable drug-deliverysystems provide new means for achieving therapeutic drug concentrations over entire treatment durations in order to optimize drug action. This article focuses on new drug administration modalities achieved using implantable drug-deliverysystems that are enabled by micro- and nano-fabrication technologies, and microfluidics. Recent advances in drug administration technologies are discussed and remaining challenges are highlighted.
Pain is an unpleasant sensory experience resulting from damage to bodily tissues. It is considered a significant public health problem because it affects 1/5 of the world population and causes loss of great amounts of money. Pain reflects a mixture of pathological, psychological and genetic conditions that need deep understanding to be efficiently treated. If under-treated, pain results in serious immune and metabolic problems. Pain management faces many problems that limit its control. For instance, efficiency of pain killers is limited, pain killers give rise to serious side effects and inability of drug administration methods to help in pain control. Technology can overcome some of these problems and the introduction of implantable controlled drugdeliverysystems (CDDS), manufactured from biodegradable materials, offers a solution. Implantable CDDS provide good level of pain control, as they continuously provide drug, reduce side effects and improve patients' compliance. Biodegradable type of implantable CDDS are polymer based devices that are fabricated to locally deliver drugs in a pre-designed manner. They are currently a focus of research in the field of pain therapy in order to explore their chance to offer an alternative to the conventional methods for drugdelivery. This paper aims to highlight the dimensions of pain issue and to overview the basics of drug release from polymers used for CDDS in pain management. In addition, it discusses the recent advances in the technologically designed drugdeliverysystems in the field of pain medicine and their clinical applications. Future perspectives are also presented. PMID:17159768
Al Malyan, M; Becchi, C; Boncinelli, S; Ashammakhi, N
In recent years scientific and technological advancements have been made in the research and development of rate-controlled oral drugdeliverysystems by overcoming physiological adversities, such as short gastric residence times (GRT) and unpredictable gastric emptying times (GET). Several approaches are currently utilized in the prolongation of the GRT, including floating drugdeliverysystems (FDDS), also known as hydrodynamically balanced
Erodible bioadhesive drugdelivery vehicles for use in delivering pharmaceutical compounds to the eye and similar physiological environments are disclosed. The drugdelivery vehicles are formed of a homopolymer or copolymer of maleic anhydride or lower alkyl maleic anhydride incorporating a pharmaceutical compound in either a monolithic matrix or encapsulated form. The bioadhesive erodible drugdelivery vehicles are configured to be retained in the eye following administration while providing specific erosion profiles allowing convenient drugdelivery schedules ranging from hourly to daily or weekly intervals.
Numerous drugdeliverysystems (DDSs) can be used as intraocular tools to provide a sustained and calibrated release for a specific drug. Great progress has been made on the design, biocompatibility, bioavailability, and efficacy of DDSs. Although several of them are undergoing clinical trials, a few are already on the market and could be of a routine use in clinical practice. Moreover, miniaturization of the implants makes them less and less traumatic for the eye tissues and some DDSs are now able to target certain cells or tissues specifically. An overview of ocular implants with therapeutic application potentials is provided. PMID:18268450
Bourges, J-L; Touchard, E; Kowalczuk, L; Berdugo, M; Thomas-Doyle, A; Bochot, A; Gomez, A; Azan, F; Gurny, R; Behar-Cohen, F
Important classes of drugs have yet to benefit from advances in drugdelivery technology. Strategies to provide reasonable oral bioavailability of peptide and proteins drugs remain elusive, for example. Systemic cancer drugs produce dose-limiting toxicities largely due to their lack of selectivity. Although deliverysystems such as immunotoxins and liposomes improve selectivity of a few cancer drugs, current technology is
Oral drugdeliverysystems will remain the largest method used for drugdelivery. 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
Lipids have been used extensively for drugdelivery in various forms such as liposomes, and solid-matrices. The focus of this review is evaluation of liquid crystalline cubic phases, spontaneously formed when amphiphilic lipids are placed in aqueous environment, for drugdelivery. Cubic phases have an interesting thermodynamically stable structure consisting of curved bicontinuous lipid bilayer in three dimensions, separating two
Jaymin C Shah; Yogesh Sadhale; Dakshina Murthy Chilukuri
In situ forming polymeric formulations are drugdeliverysystems 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 drugdeliverysystems. 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
Background: Drugdelivery across the blood-brain barrier (BBB) is a major limitation in the treatment of central nervous system (CNS) disorders. Several approaches are being investigated to improve drugdelivery across the BBB. Objective\\/Methods: This review deals with the role of nanobiotechnology in CNS drugdelivery. The small size of the nanoparticles enables them to penetrate the BBB and facilitate
The skin acts as a major target as well as a principle barrier for topical\\/transdermal (TT) drugdelivery. The stratum corneum plays a crucial role in barrier function for TT drugdelivery. Despite major research and development efforts in TT systems and the advantages of these routes, low stratum corneum permeability limits the usefulness of topical drugdelivery. To overcome
The oral delivery of hydrophobic drugs presents a major challenge because of the low aqueous solubility of such compounds. Self-emulsifying drugdeliverysystems (SEDDS), which are isotropic mixtures of oils, surfactants, solvents and co-solvents\\/surfactants, can be used for the design of formulations in order to improve the oral absorption of highly lipophilic drug compounds. SEDDS can be orally administered in
Novel drugdeliverysystem is a novel approach to drugdelivery that addresses the limitations of the traditional drugdeliverysystems. Our country has a vast knowledge base of Ayurveda whose potential is only being realized in the recent years. However, the drugdeliverysystem 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 drugdelivery 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 drugdelivery in herbal medicines. Thus it is important to integrate novel drugdeliverysystem 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 drugdeliverysystem, such as nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, solid lipid nanoparticles and so on. This article summarizes various drugdelivery technologies, which can be used for herbal actives together with some examples.
For last five years, we are developing the novel local drugdelivery devices using biodegradable polymers, especially polylactide\\u000a (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) due to its relatively good biocompatibility, easily controlled biodegradability, good processability and\\u000a only FDA approved synthetic degradable polymers. The relationship between various kinds of drug [water soluble small molecule\\u000a drugs : gentamicin sulfate (GS), fentanyl citrate (FC), BCNU,
Gilson Khang; John M. Rhee; Je Kyo Jeong; Jeong Sik Lee; Moon Suk Kim; Sun Hang Cho; Hai Bang Lee
The skin is considered a complex organ for drugdelivery because of its structure. Drugdeliverysystems are designed for the controlled release of drugs through the skin into the systemic circulation, maintaining consistent efficacy and reducing the dose of the drugs and their related side effects. Transdermal drugdelivery represents one of the most rapidly advancing areas of novel drugdelivery. The excellent impervious nature of the skin is the greatest challenge that must be overcome for successful drugdelivery. Today, polymers have been proven to be successful for long-term drugdelivery applications as no single polymer can satisfy all of the requirements. Biopolymers in the field of dermal application are rare and the mechanisms that affect skin absorption are almost unknown. Biopolymers are widely used as drugdeliverysystems, but as such the use of biopolymers as drugdeliverysystems in dermatologic therapy is still in progress. Commonly used biopolymers include hydrocolloids, alginates, hydrogels, polyurethane, collagen, poly(lactic-co-glycolic acid), chitosan, proteins and peptides, pectin, siRNAs, and hyaluronic acid. These new and exciting methods for drugdelivery are already increasing the number and quality of dermal and transdermal therapies. This article reviews current research on biopolymers and focuses on their potential as drug carriers, particularly in relation to the dermatologic aspects of their use. PMID:20499487
Basavaraj, K H; Johnsy, George; Navya, M A; Rashmi, R; Siddaramaiah
The medication is one of the most general treatment methods, but drugs diffuse in the normal tissues other than the target part by the blood circulation. Therefore, side effect in the medication, particularly for a drug with strong effect such as anti-cancer drug, are a serious issue. DrugDeliverySystem (DDS) which accumulates the drug locally in the human body is one of the techniques to solve the side-effects. Magnetic DrugDeliverySystem (MDDS) is one of the active DDSs, which uses the magnetic force. The objective of this study is to accumulate the ferromagnetic drugs noninvasively in the deep part of the body by using MDDS. It is necessary to generate high magnetic field and magnetic gradient at the target part to reduce the side-effects to the tissues with no diseases. The biomimetic model was composed, which consists of multiple model organs connected with diverged blood vessel model. The arrangement of magnetic field was examined to accumulate ferromagnetic drug particles in the target model organ by using a superconducting bulk magnet which can generate high magnetic fields. The arrangement of magnet was designed to generate high and stable magnetic field at the target model organ. The accumulation experiment of ferromagnetic particles has been conducted. In this study, rotating HTS bulk magnet around the axis of blood vessels by centering on the target part was suggested, and the model experiment for magnet rotation was conducted. As a result, the accumulation of the ferromagnetic particles to the target model organ in the deep part was confirmed.
Chuzawa, M.; Mishima, F.; Akiyama, Y.; Nishijima, S.
The ability to inject a drug incorporated into a polymer to a localized site and have the polymer form a semi-solid drug depot has a number of advantages. Among these advantages is ease of application and localized, prolonged drugdelivery. For these reasons a large number of in situ setting polymeric deliverysystems have been developed and investigated for use
Over the past several years, photodynamic therapy (PDT) has been approved for the treatment of various cancers. Additional applications of photochemical processes for triggering site-specific drugdelivery are in early stages of development at this time. This review focuses on the literature appearing between January 1996–June 2001 that describe new and ongoing studies of phototriggering mechanisms that may ultimately find
Proteins nanoparticles are one of the new methods for food deliverysystems. The protein nanoparticles which represent promising carriers for delivery are fabricated based on different methods. Synthetic protein nanostructure acts as surrogate mimics such as viruses and plasmid for food and drugdeliverysystem. The benefits of protein nanoparticles include non-toxicity, stability for long duration, nonantigenicity and biodegradability. The
In this paper, a micro-needle array combined with transdermal delivery, as well as the detection of micro-sensors intelligent transdermal insulin deliverysystems was designed with characteristics of pain-free, smart, timing, positioning, quantitative drugdelivery. Transdermal delivery of the requirements for the design of the transdermal delivery of the microneedle array structure, and UV-LIGA process for the production of polymer micro-needle
Biodegradable injectable in situ forming drugdeliverysystems represent an attractive alternative to microspheres and implants as parenteral depot systems. Their importance will grow as numerous proteins will lose their patent protection in the near future. These devices may offer attractive opportunities for protein delivery and could possibly extend the patent life of protein drugs. The controlled release of bioactive
C. B Packhaeuser; J Schnieders; C. G Oster; T Kissel
In the last two decades colon targeted drugdelivery has gained increased importance not just for the deliver drugs for the treatment of various colonic diseases but also for its potential for delivery of proteins and therapeutic peptides. In the past various traditional approaches used for colon targeted delivery like prodrugs, pH, time dependent, and microflora activated systems, have achieved limited success. For successful colon targeted drugdelivery, the drug needs to be protected from absorption and/or the environment of the upper gastrointestinal tract and then be abruptly released into the colon. Hence continuous efforts have been made on designing colon targeted drugdeliverysystems with improved site specificity and versatile drug release kinetics to fulfill different therapeutic needs. In last couple of years few new systems have been developed for colon targeted drugdelivery such as pressure dependent systems, CODES technology, microsponges, pectin and galactomannan coating, microbially triggered osmotic systems, lectins and neoglyconjugated etc. which are reported to have better in-vivo site specificity and design rationale than the earlier approaches. This review article gives an overview of various approaches for colonic targeted drugdelivery with emphasis on newer systems, their merits and demerits, in vitro/ in-vivo evaluation and market status of such deliverysystems. PMID:18673262
In these years, ordered mesoporous silica materials have shown promising applications in drugdeliverysystem as drug carriers. These carriers with stable mesoporous structure, large surface area, good biocompatibility and tailored size of mesopores exhibit significant property of higher drug loading. However, silica-based mesoporous materials cannot control the release of the loaded drug without modifications. In this paper, we review the recent research work discussing functionalization of mesoporous materials by various components and methods for application in drugdeliverysystems. All the examples show that these functionalized mesoporous silica-based systems have great potential for a variety of drugdelivery applications, specifically in the fields of the drug targeted and controlled deliverysystems. PMID:22512562
Transdermal route has been recognized as a promising drugdeliverysystem for systemicdelivery of drugs and provides the advantage of avoidance of first-pass effect, ease of use, better patient compliance, maintaining constant blood level for longer period of time and decrease side effects. The major pitfalls of this route lie with difficulty in permeation of drugs through the skin. Several literatures have been published for enhancing the permeation of drugs by chemical approaches. However the present review highlighted about the advanced physical techniques used for enhancing delivery of drugs such as structure-based, electrically based, velocity based and several other miscellaneous physical techniques for enhancing the permeation of drugs. In addition to these, the present review also gives an exhaustive account on clinical data about these techniques and regulatory considerations for new drugs as well as generic product approval in transdermal drugdelivery. PMID:21453254
Swain, Suryakanta; Beg, Sarwar; Singh, Astha; Patro, Ch Niranjan; Rao, M E Bhanoji
Lipid-based deliverysystems are finding increasing application in the oral delivery of poorly water-soluble, lipophilic drugs. Whilst lipidic dose forms may improve oral bioavailability via several mechanisms, enhancement of gastrointestinal solubilisation remains argueably the most important method of absorption enhancement. This review firstly describes the mechanistic rationale which underpins the use of lipid-based deliverysystems to enhance drug solubilisation and
Christopher J. H. Porter; Colin W. Pouton; Jean F. Cuine; William N. Charman
Nanoemulsions have received a growing attention as colloidal drug carriers for pharmaceutical applications. Their advantages over conventional formulations include drug enhanced solubility and bioavailability, protection from toxicity, improved pharmacological activity and stability, more sustained delivery and protection from physical and chemical degradation. Nanoemulsions can be prepared by two major techniques, high-energy and low-energy emulsification. Both these emulsification methods have proved to be efficient to obtain stable nanoemulsions with small and highly uniform droplets. Further research into nanoemulsions is important to develop novel liquid formulations with more efficient results in therapeutic. PMID:22755138
de Campos, Vania E B; Ricci-Júnior, Eduardo; Mansur, Claudia R E
Microemulsions are clear, stable, isotropic mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drugdelivery vehicles by incorporating a wide range of drug molecules. In order to appreciate the potential of microemulsions as delivery vehicles, this review gives
Liposomal drug-deliverysystems have come of age in recent years, with several liposomal drugs currently in advanced clinical trials or already on the market. It is clear from numerous pre-clinical and clinical studies that drugs, such as antitumor drugs, packaged in liposomes exhibit reduced toxicities, while retaining, or gaining enhanced, efficacy. This results, in part, from altered pharmacokinetics, which lead
The need for safe, therapeutically effective and patient-compliant drugdeliverysystems continuously leads researchers to design novel tools and strategies. Clay minerals are widely used materials in drug products both as excipients and active agents. When administered simultaneously, drug–clay interactions have been observed and studied, but until recently were not considered as a possible mechanism to modify drug release. In
Polyurethanes (PUs) are formed by a reaction between isocyanates and diols to yield polymers with urethane bonds (-NH-COO-) in their main chain. A great variety of building blocks is commercially available that allows the chemical and physical properties of PUs to be tailored to their target applications, particularly for the biomedical and pharmaceutical fields. This article reviews the synthesis and characterization of PUs and PU-copolymers, as well as their in vitro and in vivo biodegradability and biocompatibility. Particular emphasis is placed on the use of PUs for the controlled release of drugs and for the (targeted) delivery of biotherapeutics. PMID:23632262
Cherng, Jong Yuh; Hou, Ting Yi; Shih, Mei Fen; Talsma, Herre; Hennink, Wim E
Current research in the field of drugdelivery devices, by which pulsatile release is achieved, has been intensified. In this article, an attempt has been made to discuss several types of drugdeliverysystems that show pulsatile drugdelivery characteristics. As found frequently in the living body, many vital functions are regulated by pulsed or transient release of bioactive substances at a specific site and time. Thus it is important to develop new drugdelivery devices to achieve pulsed delivery of a certain amount of drugs in order to mimic the function of the living systems, while minimizing undesired side-effects. Pulsatile delivery, which is meant as the liberation of drugs following programmed lag phases, has drawn increasing interest, especially in view of emerging chronotherapeutic approaches. This review article is an attempt to discuss various design strategies, chiefly including reservoir, capsular, and osmotic formulations, and drugdeliverysystems which cause the pulsed or triggered release of bioactive compounds induced due to certain stimuli like thermal, electrical, and magnetic. PMID:21138394
Continuous, ‘infusion-like’ drug release profiles from biodegradable parenteral deliverysystems are difficult to achieve for proteins and other hydrophilic macromolecular drugs with commonly used linear polyesters from lactic acid (PLA) and its random copolymers with glycolic acid (PLG). Drug release rates can be modified either by increasing the hydrophilicity of polyesters or by manipulating the polymer architecture to adjust polymer
The objective of the present study is to develop colon targeted drugdeliverysystems for mebendazole using guar gum as a carrier. Matrix tablets containing various proportions of guar gum were prepared by wet granulation technique using starch paste as a binder. The tablets were evaluated for drug content uniformity, and were subjected to in vitro drug release studies. The
Y. S. R Krishnaiah; P Veer Raju; B Dinesh Kumar; P Bhaskar; V Satyanarayana
Drug synthesis and discovery represents today one of the most rapidly evolving scientific areas. This is primarily due to the interdisciplinary collaboration between chemists, pharmacologists, molecular biologists, and biochemists. A direct implication of the developments in drug discovery is the need for novel drugdeliverysystems and devices. Considering the advances in engineering disciplines and micro\\/nano technology the potential for
Leonidas Bleris; Panagiotis Vouzis; Mark V. Arnold; Mayuresh V. Kothare
A drugdeliverysystem has been envisioned employing actinmyosin molecular motors, liposomes, microcantilevers and a specific track formed by microfilaments. Molecular motors can pull on giant liposomes enclosing the drug to be delivered at the target site. An array of microcantilevers whose deflection in nanometers would cause the opening of the valves responsible for delivering the drug, would be implanted
S. K. Vashist; R. Tewari; I. Kaur; R. P. Bajpai; L. M. Bharadwaj
The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drugdeliverysystem together with factors affecting the system. This deliverysystem utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemicdelivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application.
Osmotically controlled oral drugdeliverysystems utilize osmotic pressure for controlled delivery of active agent(s). Drugdelivery from these systems, to a large extent, is independent of the physiological factors of the gastrointestinal tract and these systems can be utilized for systemic as well as targeted delivery of drugs. The release of drug(s) from osmotic systems is governed by various
The study of radiation polymerization in a super-cooled state started in 1966 and has been applied to the immobilization of biofunctional materials since 1973. In the last twenty years, application has been concentrated to the immobilization of drugs and hormones for the purpose of drugdeliverysystems. Very recently, the author has proposed a concept of environmental signal responsive chemical deliverysystem, as a new generation of controlled release and deliverysystems. The study and development of materials, devices and systems is described. The signal responsive deliverysystem consists of a sensor part and a controlled delivery part. Therefore, the use of immobilization techniques for the biochip sensor and the hydrogel actuator has been investigated. As a future goal, systems for the brain research are to be designed and studied.
The invention is directed to a drugdelivery device for controlled release of a drug, comprising a core that has a cylindrical plug embedded therein; and a coating that at least partially surrounds the core. The core is comprised of a drug and excipients. The coating surrounding the core is essentially impermeable to the drug. The cylindrical plug, which is embedded in the core, may be hollow or solid. The drugdelivery device enables zero-order drug release profiles as well as more complicated release profiles to be obtained. The invention is also directed to a method of making the drugdelivery device.
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 deliverysystems 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 deliverysystems 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 deliverysystems 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.
Rajan, Reshmy; Jose, Shoma; Mukund, V. P. Biju; Vasudevan, Deepa T.
For effective chemotherapy, it is necessary to deliver therapeutic agents selectively to their target sites, since most drugs are associated with both beneficial effects and side effects. The use of lipid dispersion carrier systems, such as lipid emulsions and liposomes, as carriers of lipophilic drugs has attracted particular interest. A drugdeliverysystem can be defined as a methodology for manipulating drug distribution in the body. Since drug distribution depends on the carrier, administration route, particle size of the carrier, lipid composition of the carrier, electric charge of the carrier and ligand density of the targeting carrier, these factors must be optimized. Recently, the lipid carrier system has also been applied to gene deliverysystems for gene therapy. However, in both drug and gene medicine cases, a lack of cell-selectivity limits the wide application of this kind of drug and/or gene therapy. Therefore, lipid carrier systems for targeted drug and gene delivery must be developed for the rational therapy. In this review, we shall focus on the progress of research into lipid carrier systems for drug and gene delivery following systemic or local injection. PMID:16079512
Over the last few decades, colloidal drugdeliverysystems (CDDS) such as nano-structures have been developed in order to improve the efficiency and the specificity of drug action. Their small size permits them to be injected intravenously in order to reach target tissues. However, it is known that they can be rapidly removed from blood circulation by the immune system.
Arnaud Vonarbourg; Catherine Passirani; Patrick Saulnier; Jean-Pierre Benoit
In the arena of solubility enhancement, several problems are encountered. A novel approach based on lipid drugdeliverysystem 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 deliverysystem 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 drugdeliverysystem.
Targeting drugdeliverysystem (TDDS) is one of the most concerned research fields in cancer treatment because it can bind selectively and react with the target diseased sites at the cellular or sub-cellular level, making distribution and release of drugs in a controlled manner, thus enhance therapeutic effects and reduce toxic and side-effects on normal cells. Polyamidoamine dendrimer (PAMAMD) is a kind of newly developed polymer in nanometer degree. Hyper-branched, monodispersity, three-dimensional structure and host-guest entrapment ability make it used as drug carrier, gene deliverysystem and imaging agent. Various targeting ligands, which have high affinity to specific organs, tissues or cells in human body, can be linked to surface functional groups of PAMAMD. And drugs and theoretical gene are carried by encapsulation or chemical conjugation. Finally, PAMAMD targeting drugdeliverysystem can carry drugs and theoretical gene to diseased sites and then release them for targeted therapy. The PAMAMD-based conjugates have small size, ligh permeability and retention effect (EPR), low toxicity and so on. The research progress of PAMAMD modified by different ligands in targeting drugdeliverysystem is reviewed, and research direction of the PAMAMD targeting deliverysystem in the future is also suggested. PMID:21800534
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 deliverysystems, with not much success in the past. With the advancement in the field of chronobiology, modern drugdelivery 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 deliverysystem 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 deliverysystems. This review on chronopharmaceutics based delivery lays emphasis on the existing technologies and future development. PMID:22564168
A recent important advance in biopharmaceutics has been the utilization of controlled delivery of drugs to the systemic circulation through the intact skin. With the conventional tablet and capsule dosage forms, the amount of drug absorbed through the gastrointestinal (GI) tract varies depending on the quan tity and types of food in the stomach, on the GI motility and transit
Self-emulsifying drugdeliverysystems (SEDDS) are mixtures of oils and surfactants, ideally isotropic, sometimes including cosolvents, which emulsify under conditions of gentle agitation, similar to those which would be encountered in the gastro-intestinal tract. Hydrophobic drugs can often be dissolved in SEDDS allowing them to be encapsulated as unit dosage forms for peroral administration. When such a formulation is released
The inclusions in a typical transdermal drugdeliverysystem (TDS) containing estradiol drug were characterized using microscopic, spectroscopic and thermal analytical techniques. Optical and scanning electron microcscopy were used to determine the locations and morphologies of the crystals in the matrix. Two different types of crystals randomly distributed laterally inside the patch were observed. Solid aggregates were found surrounding needle-like
A mathematical model of iontophoretic transdermal drugdelivery was applied to study the effects of physical parameters on the cumulative amount of amitriptyline HCl collected. A graphical method, based on an analytical solution of the system, was first used to estimate the drug diffusion coefficient in the membrane and its surface concentration in the absence of an electric potential difference.
This review will provide an in-depth discussion on the previous development of nanoparticle-based drugdeliverysystems (DDS) and discuss original research data that includes the therapeutic enhancement of antiretroviral therapy. The use of nanoparticle DDS will allow practitioners to use drugs to target specific areas of the body. In the treatment of malignancies, the use of nanoparticles as a DDS
Jeffrey D. Kingsley; Huanyu Dou; Justin Morehead; Barrett Rabinow; Howard E. Gendelman; Christopher J. Destache
Electrospinning and electrospraying are facile electrohydrodynamic fabrication methods that can generate drugdeliverysystems (DDS) through a one-step process. The nano-structured fiber and particle morphologies produced by these techniques offer tunable release kinetics applicable to diverse biomedical applications. Coaxial-electrospinning/electrospraying, a relatively new technique of fabricating core-shell fibers/particles have added to the versatility of these DDS by affording a near zero-order drug release kinetics, dampening of burst release, and applicability to a wider range of bioactive agents. Controllable electrospinning/spraying of fibers and particles and subsequent drug release from these chiefly polymeric vehicles depends on well-defined solution and process parameters. The additional drugdelivery capability from electrospun fibers can further enhance the material’s functionality in tissue engineering applications. This review discusses the state-of-the-art of using electrohydrodynamic technique to generate nano-fiber/particles as drugdelivery devices.
Chakraborty, Syandan; Liao, I-Chien; Adler, Andrew; Leong, Kam W.
Electrospinning and electrospraying are facile electrohydrodynamic fabrication methods that can generate drugdeliverysystems (DDS) through a one-step process. The nanostructured fiber and particle morphologies produced by these techniques offer tunable release kinetics applicable to diverse biomedical applications. Coaxial electrospinning/electrospraying, a relatively new technique of fabricating core-shell fibers/particles have added to the versatility of these DDS by affording a near zero-order drug release kinetics, dampening of burst release, and applicability to a wider range of bioactive agents. Controllable electrospinning/spraying of fibers and particles and subsequent drug release from these chiefly polymeric vehicles depends on well-defined solution and process parameters. The additional drugdelivery capability from electrospun fibers can further enhance the material's functionality in tissue engineering applications. This review discusses the state-of-the-art of using electrohydrodynamic technique to generate nanofiber/particles as drugdelivery devices. PMID:19651167
Chakraborty, Syandan; Liao, I-Chien; Adler, Andrew; Leong, Kam W
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-deliverysystems (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
The current advances in chronobiology and the knowledge gained from chronotherapy of selected diseases strongly suggest that “the one size fits all at all times” approach to drugdelivery is no longer substantiated, at least for selected bioactive agents and disease therapy or prevention. Thus, there is a critical and urgent need for chronopharmaceutical research (e.g., design and evaluation of robust, spatially and temporally controlled drugdeliverysystems that would be clinically intended for chronotherapy by different routes of administration). This review provides a brief overview of current deliverysystem intended for chronotherapy. In theory, such an ideal “magic pill” preferably with affordable cost, would improve the safety, efficacy and patient compliance of old and new drugs. However, currently, there are three major hurdles for the successful transition of such system from laboratory to patient bedside. These include the challenges to identify adequate (i) rhythmic biomaterials and systems, (ii) rhythm engineering modeling, perhaps using system biology and (iii) regulatory guidance.
Biologically adhesive deliverysystems offer important advantages1-5 over conventional drugdeliverysystems6. Here we show that engineered polymer microspheres made of biologically erodable polymers, which display strong adhesive interactions with gastrointestinal mucus and cellular linings, can traverse both the mucosal absorptive epithelium and the follicle-associated epithelium covering the lymphoid tissue of Peyer's patches. The polymers maintain contact with intestinal epithelium
Edith Mathiowitz; Jules S. Jacob; Yong S. Jong; Gerardo P. Carino; Donald E. Chickering; Pravin Chaturvedi; Camilla A. Santos; Kavita Vijayaraghavan; Sean Montgomery; Michael Bassett; Craig Morrell
Recently, TDDS (Targeting drugdeliverysystem) plays an important role in enhancing the bioavailability and targeting of anti-tumor drugs. How to transport drugs quickly and precisely to their target sites of action has not been solved fundamentally. A large number of researches have identified artemisinin and its analogs have the merit of precisely targeting to cancer cell, and low side effects to healthy tissue. Thus, if these compounds could be attached to established anti-tumor drugs with probe, a novel targeting anti-tumor drugs will be put into practice in the future. The novel drugsdeliverysystem will be a powerful weapon against cancer disease for their unique targeting. PMID:18829175
Controlled-release drugdelivery technology has had a significant effect on the pharmacotherapy of cardiovascular diseases. Oral and transcutaneous controlled-release systems allow relatively short-acting drugs to be administered once or twice daily with comparable therapeutic efficacy and fewer adverse reactions compared with standard formulations. They can provide decreased fluctuations in drug concentrations in plasma while possibly reducing the total amount of
Baruch Katz; Andrew Rosenberg; William H. Frishman
Transdermal drugdelivery 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 deliverysystems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation deliverysystems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted
The introduction of new topical drugs based on new chemical entities has become a rare event. Instead, pharmaceutical companies have been focused on reformulating existing drugs resulting in an ever-growing number of topical drug products for every approved drug substance. In light of this trend, soon reformulations may not be as rewarding to their sponsors as they are today unless they offer a substantial improvement over other formulations of the same drug substance and the same indication, namely improved efficacy over existing drugs, reduced side effects, unique drug combinations, or applicability for new indications. This article reviews and compares topical drugdeliverysystems currently under active research that are designed to offer such advantages in the coming years. The reviewed deliverysystems are: liposomes, niosomes, transferosomes, ethosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrin, and sol-gel microcapsules. Among all the topical drugdeliverysystems currently undergoing active research, only the sol-gel microencapsulation is at clinical stages. PMID:22353154
Fireman, Sharon; Toledano, Ofer; Neimann, Karine; Loboda, Natalia; Dayan, Nava
The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as drugdeliverysystems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of drugs. These advances have led to numerous clinical trials in such diverse areas as the delivery of anti-cancer, anti-fungal and antibiotic drugs, the delivery of gene medicines, and the delivery of anesthetics and anti-inflammatory drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine deliverysystem to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future. PMID:23036225
Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate deliverysystem to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drugdeliverysystem for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drugdeliverysystem for simvastatin.
Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate deliverysystem to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drugdeliverysystem for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drugdeliverysystem for simvastatin. PMID:23349949
Microwave has received a widespread application in pharmaceuticals and food processing, microbial sterilization, biomedical therapy, scientific and biomedical analysis, as well as, drug synthesis. This paper reviews the basis of application of microwave to prepare pharmaceutical dosage forms such as agglomerates, gel beads, microspheres, nanomatrix, solid dispersion, tablets and film coat. The microwave could induce drying, polymeric crosslinkages as well as drug-polymer interaction, and modify the structure of drug crystallites via its effects of heating and/or electromagnetic field on the dosage forms. The use of microwave opens a new approach to control the physicochemical properties and drugdelivery profiles of pharmaceutical dosage forms without the need for excessive heat, lengthy process or toxic reactants. Alternatively, the microwave can be utilized to process excipients prior to their use in the formulation of drugdeliverysystems. The intended release characteristics of drugs in dosage forms can be met through modifying the physicochemical properties of excipients using the microwave. PMID:18393808
This paper describes the development and characterization of a micro-fluidic system which comprises of a micro-pump, passive micro-valve and its control circuit. Some applications for such a system include micro-coolant systems, micro-chemical analysis systems and fluid handling systems. Micro-fluidic systems are generally application specific and the focus of the proposed system is for drugdelivery. The micro-pump is of the
A new adaptive control algorithm, the Control Advance Moving Average Controller (CAMAC), was implemented in a drugdeliverysystem to control mean arterial pressure by the infusion of sodium nitroprusside. The CAMAC, which is designed to control non-minimum-phase systems with unknown or varying dead times, is presented here. The control law minimizes a cost function at a time advance which
The present research is aimed to improve the oral delivery of paliperidone by loading into self emulsifying drugdeliverysystems (SEDDS). Oleic acid, tween 80 and capmul MCM L8 were selected as oil, surfactant and co-surfactant respectively and phase diagram was constructed and the region was identified for the formation of SEDDS. The stable formulations were analyzed for globule size,
Swetha Kanuganti; Raju Jukanti; Prabhakar R. Veerareddy; Suresh Bandari
The central nervous system (CNS) poses a unique challenge for drugdelivery. The blood-brain barrier significantly hinders the passage of systemically-delivered therapeutics and the brain extracellular matrix limits the distribution and longevity of locally-delivered agents. Polymeric nanoparticles represent a promising solution to these problems. Over the past 40 years, substantial research efforts have demonstrated that polymeric nanoparticles can be engineered for effective systemic and local delivery of therapeutics to the CNS. Moreover, many of the polymers used in nanoparticle fabrication are both biodegradable and biocompatible, thereby increasing the clinical utility of this strategy. Here, we review the major advances in the development of polymeric nanoparticles for drugdelivery to the CNS.
Patel, Toral; Zhou, Jiangbing; Piepmeier, Joseph M.; Saltzman, W. Mark
In conventional systemicdrugdelivery the drug is administered by intravenous injection; it then travels to the heart from where it is pumped to all regions of the body. When the drug is aimed at a small target region, this method is extremely inefficient and leads to require much larger doses than those being necessary. In order to overcome this problem a number of targeted drugdelivery methods are developed. One of these, magnetically targeted drugdeliverysystem (MT-DDS) will be a promising way, which involves binding a drug to small biocompatible magnetic particles, injecting these into the blood stream and using a high gradient magnetic field to pull them out of suspension in the target region. In the present paper, we describe an ex vivo experimental work. It is also reported that navigation and accumulation test of the magnetic particles in the Y-shaped glass tube was performed in order to examine the threshold of the magnetic force for accumulation. It is found that accumulation of the magnetic particles was succeeded in the blood vessel when a permanent magnet was placed at the vicinity of the blood vessel. This result indicates the feasibility of the magnetically drug targeting in the blood vessel.
This work investigated the application of a porous polyaniline (PANi) membrane as a conducting polymeric membrane as well as an electrode in an iontophoretic transdermal drugdelivery (TDD) system. Model drugs studied were: caffeine (MW: 194.2), lidocaine HCl (MW: 270.8) and doxycycline HCl (MW: 480.1). The PANi membrane was first tested as a simple membrane between the donor and receptor
Natural polysaccharides, due to their outstanding merits, have received more and more attention in the field of drugdeliverysystems. In particular, polysaccharides seem to be the most promising materials in the preparation of nanometeric carriers. This review relates to the newest developments in the preparation of polysaccharides-based nanoparticles. In this review, four mechanisms are introduced to prepare polysaccharides-based nanoparticles,
The design, synthesis, and properties of novel stimuli-sensitive and genetically engineered biomaterials and drugdeliverysystems are reviewed. Two approaches to their engineering are presented. One approach is to improve the traditional methods of synthesis, as demonstrated by the example of controlled copolymerization of ?-amino acid N-carboxyanhydrides. The other approach, discussed in more detail, uses genetic engineering methods. The design
The application of the molecular imprinting technology in the design of new drugdeliverysystems (DDS) and devices useful in closely related fields, such as diagnostic sensors or biological traps, is receiving increasing attention. Molecular imprinting technology can provide polymeric materials with the ability to recognize specific bioactive molecules and with a sorption\\/release behaviour that can be made sensitive to
The aim of this article is to give an introduction into mathematical modeling approaches of bioerodible controlled drugdeliverysystems and to present the most important erosion theories reported in the literature. First, important parameters such as degradation and erosion are defined and physicochemical methods for their investigation are briefly presented. Then, phenomenological empirical models as well as models based
Over the past several years, great advances have been made on development of novel drugdeliverysystems (NDDS) for plant actives and extracts. The variety of novel herbal formulations like polymeric nanoparticles, nanocapsules, liposomes, phytosomes, nanoemulsions, microsphere, transferosomes, and ethosomes has been reported using bioactive and plant extracts. The novel formulations are reported to have remarkable advantages over conventional formulations
The global aim of this research project was to develop a self-nanoemulsifying drugdeliverysystem (SNEDDS) for non-invasive delivery of protein drugs. The specific aim of this study was to develop SNEDDS formulations. An experimental design was adopted to develop SNEDDS. Fluorescent labeled beta-lactamase (FITC-BLM), a model protein, was loaded into SNEDDS through solid dispersion technique. The experimental design provided 720 compositions of different oil, surfactant, and co-surfactant at various ratios, of which 33 SNEDDS prototypes were obtained. Solid dispersion of FITC-BLM in SoyPC prepared was able to dissolve in 16 SNEDDS prototypes (approximately 2200 mU BLM in 1g SNEDDS). SNEDDS NE-12-7 (composition: Lauroglycol FCC, Cremophor EL and Transcutol; ratio: 5:4:3) formed O/W nanoemulsion with mean droplet size in the range of 22-50 nm when diluted with various pH media and different dilution factor with PBS (pH 7.4). The phase diagram of NE-12-7 indicated a broad region of nanoemulsion. BLM-loaded SNEDDS (NE-12-7) stored at 4 degrees C for 12 weeks indicated 10% loss of BLM activity. A SNEDDS was developed to load FITC-BLM into the oil phase which can spontaneously form O/W nanoemulsion upon the addition of water. PMID:18650038
This article aims to provide a comprehensive review of existing mathematical models and simulations of drug release from polymeric microspheres and of drug transport in adjacent tissues. In drugdeliverysystems, mathematical modeling plays an important role in elucidating the important drug release mechanisms, thus facilitating the development of new pharmaceutical products by a systematic, rather than trial-and-error, approach. The
Inhaled antimicrobial agents are used for the treatment of respiratory tract infections due to Gram-negative bacteria, mainly Pseudomonas aeruginosa. The effectiveness of the inhaled antimicrobial therapy is believed to correlate with the deliverysystem used. The objective of this review was to search for data supporting differentiation in clinical effectiveness between systems used for pulmonary delivery of antibiotics, including delivery using disposable nebulisers and oxygen flow. Published studies in peer-reviewed journals comparing the effectiveness of pulmonary drugdeliverysystems for antimicrobial agents were retrieved. The studies found were either in vitro or Phase I and Phase II clinical studies. Differences in in vitro parameters may affect the in vivo efficacy of the devices, and in vivo differences may imply differences in clinical effectiveness. The main difference between newer and older devices is the time needed for antibiotic delivery. Interpretation and association with clinical effectiveness is difficult. In conclusion, Phase III clinical trials comparing the clinical effectiveness of deliverysystems, including delivery using a hospital's oxygen flow and disposable nebulisers, do not exist. Cost is an important parameter, which may be counterbalanced in cystic fibrosis patients by a better quality of life and a greater adherence to treatment. PMID:19939637
Falagas, Matthew E; Michalopoulos, Argyris; Metaxas, Eugenios I
Development of a novel drugdeliverysystem was made to accumulate/navigate magnetic drugs with the help of a superconducting magnet in order to control the drugs in blood vessels located deep inside the body. In the present paper, we tested the feasibility of a novel navigation system, made by applying a strong external (magnetic) field through SmBaCuO and YBaCuO bulk superconductors in order to realize the practice of using externally applied magnetic fields for targeting the magnetic particles to a circumscribed body region.
The potential of transdermal drugdeliverysystems has been demonstrated in recent years with the approval of several medicines for use by patients who are unable to use conventional dosage routes, like oral administration or injection. To enhance the TDDS (Transdermal DrugDeliverySystem) potential to include other drug candidates, many researchers have been exploring enhancement approaches to increase the permeability of various drugs through the skin. Recently, physical enhancement systems are being reported as having big potential by many researchers. In particular, iontophoresis is a very attractive way of delivering ionized drugs by the application of an electric field to the skin. This has been marketed with some topical and systemicdrugs (lidocaine and fentanyl). Sonophoresis is also an attractive method to deliver a drug through the skin using ultrasound. Besides these technologies, various physical approaches are under study. Such technologies can be expected to deliver not only small MW compounds but also macromolecules like peptides. In this article, after looking back through the history of TDDS development, I would like to summarize with new physical and chemical approaches and outline of the new trend of TDDS development with those enhancement system. PMID:17409694
Present study is looking at the problem of integrating drugdelivery microcapsule, a bio-sensor, and a control mechanism into a biomedical drugdeliverysystem. A wide range of medical practices from cancer therapy to gastroenterological treatments can benefit from such novel bio-system. Drug release in our drugdeliverysystem is achieved by electrochemically actuating an array of polymeric valves on a set of drug reservoirs. The valves are bi-layer structures, made in the shape of a flap hinged on one side to a valve seat, and consisting of thin films of evaporated gold and electrochemically deposited polypyrrole (PPy). These thin PPy(DBS) bi-layer flaps cover access holes of underlying chambers micromachined in a silicon substrate. Chromium and polyimide layers are applied to implement "differential adhesion" to obtain a voltage induced deflection of the bilayer away from the drug reservoir. The Cr is an adhesion-promoting layer, which is used to strongly bind the gold layer down to the substrate, whereas the gold adheres weakly to polyimide. Drug actives (dry or wet) were pre-stored in the chambers and their release is achieved upon the application of a small bias (~ 1V). Negative voltage causes cation adsorption and volume change in PPy film. This translates into the bending of the PPy/Au bi-layer actuator and release of the drug from reservoirs. This design of the drugdelivery module is miniaturized to the dimensions of 200?m valve diameter. Galvanostatic and potentiostatic PPy deposition methods were compared, and potentiostatic deposition method yields film of more uniform thickness. PPy deposition experiments with various pyrrole and NaDBS concentrations were also performed. Glucose biosensor based on glucose oxidase (GOx) embedded in the PPy matrix during elechtrochemical deposition was manufactured and successfully tested. Multiple-drug pulsatile release and continuous linear release patterns can be implemented by controlling the operation of an array of valves. Varying amounts of drugs, together with more complex controlling strategies would allow creation of more complex drugdelivery patterns.
Kulinsky, Lawrence; Xu, Han; Tsai, Han-Kuan A.; Madou, Marc
This article concentrates mainly on fabrication of porous nanoparticles, its characterisation and its use for controlled release of drug. It also encompasses the strategies that have been used to translate and fabricate a wide range of particulate carriers e.g., nanospheres, liposomes, micelles, oil-in-water emulsions, with prolonged circulation and\\/or target specificity. Sol-gel technique is one of the most widely used techniques
Microsponges are polymeric deliverysystems composed of porous microspheres. They are tiny sponge-like spherical particles with a large porous surface. Moreover, they may enhance stability, reduce side effects and modify drug release favorably. Microsponge technology has many favorable characteristics, which make it a versatile drugdelivery vehicle. Microsponge Systems are based on microscopic, polymer-based microspheres that can suspend or entrap a wide variety of substances, and can then be incorporated into a formulated product such as a gel, cream, liquid or powder. The outer surface is typically porous, allowing a sustained flow of substances out of the sphere. Microsponges are porous, polymeric microspheres that are used mostly for topical use and have recently been used for oral administration. Microsponges are designed to deliver a pharmaceutical active ingredient efficiently at the minimum dose and also to enhance stability, reduce side effects, and modify drug release.
Microsponges are polymeric deliverysystems composed of porous microspheres. They are tiny sponge-like spherical particles with a large porous surface. Moreover, they may enhance stability, reduce side effects and modify drug release favorably. Microsponge technology has many favorable characteristics, which make it a versatile drugdelivery vehicle. Microsponge Systems are based on microscopic, polymer-based microspheres that can suspend or entrap a wide variety of substances, and can then be incorporated into a formulated product such as a gel, cream, liquid or powder. The outer surface is typically porous, allowing a sustained flow of substances out of the sphere. Microsponges are porous, polymeric microspheres that are used mostly for topical use and have recently been used for oral administration. Microsponges are designed to deliver a pharmaceutical active ingredient efficiently at the minimum dose and also to enhance stability, reduce side effects, and modify drug release. PMID:22247859
The aim of this investigation was to design a novel Gas Empowered DrugDelivery (GEDD) system for CO2 forced transport of peptide drugs together with mucoadhesive polymers to the surface of the small intestine. The GEDD effect of the core tablet was achieved using CO2 gas to push insulin together with the mucoadhesive excipients poly(ethyleneoxide) (PEO) and the permeation enhancer
A. M. M. Sadeghi; M. R. Avadi; Sh. Ejtemaimehr; Sh. Abashzadeh; A. Partoazar; F. Dorkoosh; M. Faghihi; M. Rafiee-Tehrani; H. E. Junginger
The most common methods for the drugdelivery 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 drugdeliverysystem . Using this device, drug concentration can be precisely controlled which enhances drug efficiency and decreases the side effects. In order to achieve responsive drugdelivery, 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.
Skin acts a major target as well as a principle barrier for topical/transdermal drugdelivery. Despite the many advantages of this system, the major obstacle is the low diffusion rate of drugs across the stratum corneum. Several methods have been assessed to increase the permeation rate of drugs temporarily. One simple and convenient approach is application of drugs in formulation with elastic vesicles or skin enhancers. Elastic vesicles are classified with phospholipid (Transfersomes((R)) and ethosomes) and detergent-based types. Elastic vesicles were more efficient at delivering a low and high molecular weight drug to the skin in terms of quantity and depth. Their effectiveness strongly depends on their physicochemical properties: composition, duration and application volume, and entrapment efficiency and application methods. This review focuses on the effect of elastic liposomes for enhancing the drug penetration and defines the action mechanism of penetration into deeper skin. PMID:18492190
In this study, the feasibility of a carbopol 934P-HPMC-based gel formulation as a vaginal drugdeliverysystem was evaluated. A vaginal fluid simulant (VFS) was utilized to simulate human vaginal mucus. The viscosity of the carbopol-HPMC gel system and VFS was examined using a cone and plate viscometer. The surface tension of VFS was measured using a capillary rising method.
This paper describes an actively-controlled architecture for drugdeliverysystems that offers high performance and volume\\u000a efficiency through the use of micromachined components. The system uses a controlled valve to regulate dosing by throttling\\u000a flow from a mechanically pressurized reservoir, thereby eliminating the need for a pump. To this end, the valve is fabricated\\u000a from a glass wafer and silicon-on-insulator
Allan Thomas Evans; Jong M. Park; Srinivas Chiravuri; Yogesh B. Gianchandani
Oral delivery of therapeutics is extremely challenging. The digestive system is designed in a way that naturally allows the degradation of proteins or peptides into small molecules prior to absorption. For systemic absorption, the intact drug molecules must traverse the impending harsh gastrointestinal environment. Technologies, such as enteric coating, with oral dosage formulation strategies have successfully provided the protection of non-peptide based therapeutics against the harsh, acidic condition of the stomach. However, these technologies showed limited success on the protection of therapeutic proteins and peptides. Importantly, inherent permeability coefficient of the therapeutics is still a major problem that has remained unresolved for decades. Addressing this issue in the context, we summarize the strategies that are developed in enhancing the intestinal permeability of a drug molecule either by modifying the intestinal epithelium or by modifying the drug itself. These modifications have been pursued by using a group of molecules that can be conjugated to the drug molecule to alter the cell permeability of the drug or mixed with the drug molecule to alter the epithelial barrier function, in order to achieve the effective drug permeation. This article will address the current trends and future perspectives of the oral delivery strategies. PMID:23220326
The eye has an environment that is specific unto itself in terms of pharmacokinetics: the inner and outer blood–retinal barriers separate the retina and the vitreous from the systemic circulation and vitreous body, which physiologically has no cellular components, occupies the vitreous cavity, an inner space of the eye, and reduces practical convection of molecules. Considering this, development of a
The brain is a delicate organ, and nature has very efficiently protected it. The brain is shielded against potentially toxic substances by the presence of two barrier systems: the blood brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB). Unfortunately, the same mechanisms that protect it against intrusive chemicals can also frustrate therapeutic interventions. Despite aggressive research, patients suffering
Shadab A. Pathan; Zeenat Iqbal; Syed M. A. Zaidi; Sushma Talegaonkar; Divya Vohra; Gaurav K. Jain; Adnan Azeem; Nitin Jain; Jigar R. Lalani; Roop K. Khar; Farhan J. Ahmad
Locally dropping the temperature in vivo is the main obstacle to the clinical use of a thermoresponsive drugdeliverysystem. In this paper, a Peltier electronic element is incorporated with a thermoresponsive thin film based drugdeliverysystem to form a new drugdelivery device which can regulate the release of rhodamine B in a water environment at 37 °C. Various current signals are used to control the temperature of the cold side of the Peltier device and the volume of water on top of the Peltier device affects the change in temperature. The pulsatile on-demand release profile of the model drug is obtained by turning the current signal on and off. The work has shown that the 2600 mAh power source is enough to power this device for 1.3 h. Furthermore, the excessive heat will not cause thermal damage in the body as it will be dissipated by the thermoregulation of the human body. Therefore, this simple novel device can be implanted and should work well in vivo. PMID:23467083
Yang, Rongbing; Gorelov, Alexander V; Aldabbagh, Fawaz; Carroll, William M; Rochev, Yury
Adhesives are a critical component in transdermal drugdelivery (TDD) devices. In addition to the usual requirements of functional adhesive properties, adhesives for TDD applications must have good biocompatibility with the skin, chemical compatibility with the drug, various components of the formulation, and provide consistent, effective delivery of the drug. This review discusses the three most commonly used adhesives (polyisobutylenes,
Lipid based drugdeliverysystems, and in particular self-emulsifying drugdeliverysystems (SEDDS), show great potential for enhancing oral bioavailability but have not been broadly applied, largely due to lack of general formulation guidance. To help understand how formulation design influences physicochemical emulsion properties and associated function in the gastrointestinal environment, a range of twenty-seven representative self-emulsifying formulations were investigated.
Fulden Buyukozturk; James C. Benneyan; Rebecca L. Carrier
Transdermal drugdeliverysystems (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 drugdeliverysystem 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
This work presents a portable transdermal drugdeliverysystem that combines a magnetically actuated micro gear pump with a microneedle array. Micropart fabrication is performed through DXRL and LIGA techniques. The manufacturing process of both micropump and microneedle array are described together with wear issues. Results show that the assembled device can deliver rates that go from 0.1 to 1.2ml\\/min
M. Matteucci; M. Casella; M. Bedoni; E. Donetti; M. Fanetti; F. De Angelis; F. Gramatica; E. Di Fabrizio
Contemporary treatment of malignant brain tumors has been hampered by problems with drugdelivery to the tumor bed. Inherent\\u000a boundaries of the central nervous system, such as the blood-brain barrier or the bloodcerebrospinal fluid barrier, and a general\\u000a lack of response to many chemotherapeutic agents have led to alternative treatment modalities. In general, all these modalities\\u000a have sought to either
The present research is aimed to improve the oral delivery of paliperidone by loading into self-emulsifying drugdeliverysystems (SEDDS). Oleic acid, Tween 80, and capmul MCM L8 were selected as oil, surfactant, and co-surfactant, respectively and phase diagram was constructed and the region was identified for the formation of SEDDS. The stable formulations were analyzed for globule size, robustness
Swetha Kanuganti; Raju Jukanti; Prabhakar R. Veerareddy; Suresh Bandari
By controlling size, nanoparticles can be effectively taken up into lymphatics. On this basis, various nanoparticles have been investigated for transporters of chemotherapeutic pharmaceuticals, but only a few were retained in the draining lymph node. Here, we present a technology using a magnetic carbon nanotubes (MNTs) deliverysystem, and it may be possible to facilitate the targeted delivery of drugs in the lymphatic tissue more effectively. Chemotherapeutic agents were incorporated into the pores of functionalized MNTs synthesized with a layer of magnetite nanoparticles on the inner surface of the nanotubes. To improve drugdelivery to cancer cells in the lymph nodes, individualized MNTs were noncovalently functionalized by folic acid (FA). By using an externally placed magnet to guide the drug matrix to the regional targeted lymph nodes, the MNTs can be retained in the draining targeted lymph nodes for several days and continuously release chemotherapeutic drugs. Selective killing of tumor cells overexpressing the folate receptors (FRs) in the lymph nodes can be achieved, as FR is overexpressed across a broad spectrum of human tumors. PMID:17910909
Yang, Feng; Fu, De Liang; Long, Jiang; Ni, Quan Xing
In this article, we review critical aspects in the area of drugdelivery. Specifically, delivery of siRNA, remote-controlled delivery, noninvasive delivery, and nanotechnology in drugdelivery are reviewed.
Timko, Brian P.; Whitehead, Kathryn; Gao, Weiwei; Kohane, Daniel S.; Farokhzad, Omid; Anderson, Daniel; Langer, Robert
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 drugdeliverysystem 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 deliverysystem 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
Ultrasound has been in use for the last three decades as amodality for diagnostic imaging in medicine. Recently, there have beennumerous reports on the application of nonthermal ultrasound energyfor targeting or controlling drug release. This new concept oftherapeutic ultrasound combined with drugs has led to much excitementin various medical fields. Ultrasound energy can enhance the effectsof thrombolytic agents such as urokinase. Therapeutic ultrasoundcatheters are currently being developed for treatment ofcardiovascular diseases. Devices with ultrasound transducers implantedin transdermal drug patches are also being evaluated for possibledelivery of insulin through the skin. Chemical activation of drugs byultrasound energy for treatment of cancers is another new fieldrecently termed “Sonodynamic Therapy”. Various examples of ultrasoundapplication are under investigation which could lead to revolutionarydrug deliverysystems in the future.
The colon is a site where both local and systemicdelivery of drugs can take place. Local delivery allows topical treatment of inflammatory bowel disease. However, treatment can be made effective if the drugs can be targeted directly into the colon, thereby reducing the systemic side effects. This review, mainly compares the primary approaches for CDDS (Colon Specific DrugDelivery)
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 drugdelivery to sensors and implants. Micro- and nanotechnologies are enabling the design of novel methods such
Controlled drugdelivery remains a research focus for public health to enhance patient compliance, drug efficiency and to reduce the side effects of drugs. Pectin, an edible plant polysaccharide, has shown potential for the construction of drugdeliverysystems for site-specific drugdelivery. Sev...
A multi-scale mathematical model for drug release of oral targeted drugdeliverysystems was developed and applied to a commercially available delayed release tablet (Asacol®) that delivers 5-aminosalicyclic acid (5-ASA) to the colon. Underlying physical and biochemical principles governing the involved processes (diffusion and dissolution) were employed to develop the mathematical description. Finite element formulation was used to numerically solve
Nahor Haddish-Berhane; Chell Nyquist; Kamyar Haghighi; Carlos Corvalan; Ali Keshavarzian; Osvaldo Campanella; Jenna Rickus; Ashkan Farhadi
The purpose of the present work was to design and optimize floating drugdeliverysystems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 3(2) full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t(50%)) and 70% (t(70%)) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t(50%) and t(70%) indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix. PMID:21694992
Kharia, A A; Hiremath, S N; Singhai, A K; Omray, L K; Jain, S K
Magnetic drugdeliverysystem (MDDS) is the method which the magnetic seeded drug is injected into a blood vessel and then controlled and accumulated by a magnet located outside of the human body. A high accumulation efficiency of the drug to a local diseased part and reduction in side-effects to normal organs are expected by using MDDS. The most important element in MDDS is a magnetic field generator. The high temperature superconducting (HTS) bulk magnet which can generate high magnetic field and magnetic field gradient extending to a point distant from the magnet in several ten millimeters is necessary to achieve the MDDS. In this study, the computer simulation and model experiment were conducted in order to confirm the applicability of MDDS to ovary of the cow body.
Purpose: Niosomes play an increasingly important role in drugdelivery as they can reduce toxicity and modify pharmacokinetic and bio-availability. Topically applied niosomes can increase the residence time of drugs in the stratum corneum and epidermis, while reducing the systemic absorption of the drug. It can act as drug containing reservoirs and the modification of the vesicular compositions or surface properties can adjust the drug release rate and the affinity for the target site. Ketoconazole is a broad spectrum Imidazole derivative useful in the treatment of superficial and systemic fungal infections. Materials and Methods: In order to improve the low skin penetration and to minimize the side effects associated with topical conventional drug administration, Ketoconazole niosomes were prepared by a thin film hydration method using different ratios of non-ionic surfactants (Span 40, 60 and Tween 60) along with cholesterol (CHO). The formulations were evaluated for size, shape, entrapment efficiency and in vitro drug release. Results: Niosomes appeared spherical in shape and size range was found to be 4.86 ± 1.24-7.38 ± 3.64 ?m. The entrapment efficiency was found in the range of 55.14 ± 2.29-78.63 ± 0.91% and in vitro drug release in the range of 46.63 ± 0.95-72.37 ± 0.59% in 24 h. Ketoconazole niosomes formulated with Span 60 and CHO in the ratio of 1:0.2 were found to be promising and were incorporated into 1% Carbopol gel. The formulated gel was evaluated for various physicochemical parameters and antifungal activity. The in vitro drug release study was carried out using phosphate buffer saline pH 7.4 and was found to be 36.18 ± 1.50% in 12 h. Conclusion: Gel formulation containing niosomes loaded with Ketoconazole showed prolonged action than formulations containing Ketoconazole in non-niosomal form and it can be developed successfully to improve the antifungal activity.
Shirsand, SB; Para, MS; Nagendrakumar, D; Kanani, KM; Keerthy, D
Although preformed polymers are commercially available for use in the design and development of drugdeliverysystems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drugdelivery properties of polymers. This review brings to\\u000a light the benefits of in situ polymerization for oral drugdelivery and the possibilities it provides
Ndidi Ngwuluka; Joseph Reo; Linda Felton; Stephen Howard
Colon targeting drugdeliverysystems have attracted many researchers due to the distinct advantages they present such as near neutral pH, longer transit time and reduced enzymatic activity. Moreover, in recent studies, colon specific drugdeliverysystems are gaining importance for use in the treatment of local pathologies of the colon and also for the systemicdelivery of protein and
The successful production of effective nanoparticulate drugdeliverysystems depends on maintaining the characteristics of the starting materials and the final formulation. Since compendial standards for traditional drugdeliverysystems do not always apply to nanosystems, analytical procedures for nanosized deliverysystems must be established. This will ensure the quality of such products as they reach the marketplace. Size exclusion
Daniel P. Otto; Hermanus C. M. Vosloo; Melgardt M. de Villiers
Drugdelivery technology is emerging as an interdisciplinary science aimed at improving human health. The controlled delivery of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing drugdeliverysystems. Over the past few decades, there has been considerable interest in developing biodegradable drug carriers as effective drugdeliverysystems. Polymeric materials from natural sources play an important role in controlled release of drug at a particular site. Polyhydroxyalkanoates, due to their origin from natural sources, are given attention as candidates for drugdelivery materials. Biodegradable and biocompatible polyhydroxyalkanoates are linear polyesters produced by microorganisms under unbalanced growth conditions, which have emerged as potential polymers for use as biomedical materials for drugdelivery due to their unique physiochemical and mechanical properties. This review summarizes many of the key findings in the applications of polyhydroxyalkanoates and polyhydroxyalkanoate nanoparticles for drugdeliverysystem.
Shrivastav, Anupama; Kim, Hae-Yeong; Kim, Young-Rok
Drugdelivery technology is emerging as an interdisciplinary science aimed at improving human health. The controlled delivery of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing drugdeliverysystems. Over the past few decades, there has been considerable interest in developing biodegradable drug carriers as effective drugdeliverysystems. Polymeric materials from natural sources play an important role in controlled release of drug at a particular site. Polyhydroxyalkanoates, due to their origin from natural sources, are given attention as candidates for drugdelivery materials. Biodegradable and biocompatible polyhydroxyalkanoates are linear polyesters produced by microorganisms under unbalanced growth conditions, which have emerged as potential polymers for use as biomedical materials for drugdelivery due to their unique physiochemical and mechanical properties. This review summarizes many of the key findings in the applications of polyhydroxyalkanoates and polyhydroxyalkanoate nanoparticles for drugdeliverysystem. PMID:23984383
Shrivastav, Anupama; Kim, Hae-Yeong; Kim, Young-Rok
This is a summary report of the conference on drug absorption and bioequivalence issues held in Titania Hotel in Athens (Greece)\\u000a from the 28th to the 30th of May 2009. The conference included presentations which were mainly divided into three sections. The first section focused\\u000a on modern drugdeliverysystems such as polymer nanotechnology, cell immobilization techniques to deliver drugs
Vangelis Karalis; Eleni Magklara; Vinod P. Shah; Panos Macheras
Alginate based microparticle drugdeliverysystems were prepared for the sustained release of antineoplastic drugs. Two drugs, 5-fluorouracil (5-FU) and tegafur, were encapsulated into the microparticles. The drug loaded microparticles were fabricated using a very convenient method under very mild conditions, i.e., directly shredding the drug loaded beads into microparticles in a commercial food processor. The mean sizes of the obtained microparticles were between 100 and 200 microm. To effectively sustain the drug release, alginate microparticles were reinforced by chitosan during gelation. The drug release from the chitosan-reinforced alginate microparticles was obviously slower than that from the unreinforced microparticles. The effect of the reinforcement conditions on the drug release property of the microparticles was studied, and the optimized concentration of chitosan solution for reinforcement was identified. The effects of drug feeding concentration and pH value of the release medium on the drug release were investigated. PMID:18313867
Leishmaniasis is a complex of diseases with numerous clinical manifestations for instance harshness from skin lesions to severe disfigurement and chronic systemic infection in the liver and spleen. So far, the most classical leishmaniasis therapy, despite its documented toxicities, remains pentavalent antimonial compounds. The arvailable therapeutic modalities for leishmaniasis are overwhelmed with resistance to leishmaniasis therapy. Mechanisms of classical drug resistance are often related with the lower drug uptake, increased efflux, the faster drug metabolism, drug target modifications and over-expression of drug transporters. The high prevalence of leishmaniasis and the appearance of resistance to classical drugs reveal the demand to develop and explore novel, less toxic, low cost and more promising therapeutic modalities. The review describes the mechanisms of classical drug resistance and potential drug targets in Leishmania infection. Moreover, current drug-deliverysystems and future perspectives towards Leishmaniasis treatment are also covered. PMID:24144417
Yasinzai, Masoom; Khan, Momin; Nadhman, Akhtar; Shahnaz, Gul
An electro-sensitive transdermal drugdeliverysystem was prepared by the electrospinning method to control drug release. A semi-interpenetrating polymer network was prepared as the matrix with polyethylene oxide and pentaerythritol triacrylate polymers. Multi-walled carbon nanotubes were used as an additive to increase the electrical sensitivity. The release experiment was carried out under different electric voltage conditions. Carbon nanotubes were observed
Nasal drugdelivery is an attractive approach for the systemicdelivery of high potency drugs with a low oral bioavailability due to extensive gastrointestinal breakdown and high hepatic first-pass effect. For lipophilic drugs nasal delivery is possible if they can be dissolved in the dosage form. Peptide and protein drugs often have a low nasal bioavailability because of their large
F. W. H. M Merkus; J. C Verhoef; E Marttin; S. G Romeijn; P. H. M van der Kuy; W. A. J. J Hermens; N. G. M Schipper
The colon is a site where both local and systemicdelivery of drugs can take place. Local delivery allows topical treatment of inflammatory bowel disease. However, treatment can be made effective if the drugs can be targeted directly into the colon, thereby reducing the systemic side effects. This review, mainly compares the primary approaches for CDDS (Colon Specific DrugDelivery) namely prodrugs, pH and time dependent systems, and microbially triggered systems, which achieved limited success and had limitations as compared with newer CDDS namely pressure controlled colonic delivery capsules, CODESTM, and osmotic controlled drugdelivery which are unique in terms of achieving in vivo site specificity, and feasibility of manufacturing process.
Inhaled antimicrobial agents are used for the treatment of respiratory tract infections due to Gram-negative bacteria, mainly Pseudomonas aeruginosa. The effectiveness of the inhaled antimicrobial therapy is believed to correlate with the deliverysystem used. The objective of this review was to search for data supporting differentiation in clinical effectiveness between systems used for pulmonary delivery of antibiotics, including delivery
Matthew E. Falagas; Argyris Michalopoulos; Eugenios I. Metaxas
The adriamycin and galactose was grafted to dextran. The novel nanopartcile drugdeliverysystem (DDS) was prepared from the chemical modified polysaccharide by the dialysis. The content of the ADR moiety in the polymeric-drug conjugate was about 2 mol%. The size and morphology of prepared nanoparticles were characterized using dynamic light scattering and transmission electron microscope. The results showed that the nanoparticles were spherical and their size was less than 200 nm. In vitro cytotoxicity of the nanoparticles was tested by the MTT assay. The nano DDS has similar cytotoxicity as free adriamycin for incubation with HepG2 cells. In contrast, for the incubation with Hela cells of the DDS, there was no signicant cytotoxicity change.
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 drugdelivery 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
Summary The unique requirements of peptides and proteins in designing deliverysystems, and the unprecedented recent growth in the\\u000a field, has driven a great deal of research into novel means of drugdelivery. The search for approaches that provide formulations\\u000a that are stable, bioavailable, readily manufacturable, and acceptable to the patient, has led to major advances in development\\u000a of nasal and
Microfabrication techniques which permit the creation of therapeutic deliverysystems that possess a combination of structural, mechanical, and perhaps electronic features may surmount challenges associated with conventional delivery of therapy. In this review, delivery concepts are presented which capitalize on the strengths of microfabrication. Possible applications include micromachined silicon membranes to create implantable biocapsules for the immunoisolation of pancreatic islet
The use of gelatin for growth factor delivery was investigated. Protein-gelatin interactions were characterized using the Biomolecular Interaction Detection (BIND) system. Acidic gelatin sheets and basic gelatin microspheres were fabricated and optimized for delivering transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP)-2. The two delivery vehicles were then combined to produce two distinct release sequences and the effect of sequence on bone healing was determined. Using the BIND system, TGF-beta1 was found to interact more strongly with acidic gelatin than basic gelatin whereas BMP-2 only slightly favors basic gelatin over acidic gelatin. Acidic gelatin sheets were fabricated by a casting technique. These sheets successfully delivered TGF-beta1 to a rabbit ulna defect to encourage new bone formation. Basic gelatin microspheres were fabricated by the precision particle fabrication (PPF) method. Uniform drug distribution within the microspheres lead to controlled release of BMP-2 that induced bone formation within the thigh muscle of mice. The sheets and microspheres were combined to deliver both drugs either simultaneously or with a four-day delay to a rabbit calvarial defect. Both sequences encouraged more bone regeneration than empty defects by 8 weeks. Protein-gelatin interactions improved protein stability and lead to release through enzymatic degradation of the gelatin. Growth factors released either singly or in a dual system from gelatin successfully produced bone in vivo. However, single release systems require higher dosages to achieve similar healing results as observed in the dual release systems. No difference was observed between the dual release systems investigated.
The present work introduces new biohybrid materials involving layered double hydroxides (LDH) and biopolymers to produce bionanocomposites, able to act as effective drugdeliverysystems (DDS). Ibuprofen (IBU) and 5-aminosalicylic acid (5-ASA) have been chosen as model drugs, being intercalated in a Mg-Al LDH matrix. On the one side, the LDHIBU intercalation compound prepared by ion-exchange reaction was blended with the biopolymers zein, a highly hydrophobic protein, and alginate, a polysaccharide widely applied for encapsulating drugs. On the other side, the LDH- 5-ASA intercalation compound prepared by co-precipitation was assembled to the polysaccharides chitosan and pectin, which show mucoadhesive properties and resistance to acid pH values, respectively. Characterization of the intercalation compounds and the resulting bionanocomposites was carried out by means of different experimental techniques: X-ray diffraction, infrared spectroscopy, chemical and thermal analysis, as well as optical and scanning electron microscopies. Data on the swelling behavior and drug release under different pH conditions are also reported.
Aranda, Pilar; Alcântara, Ana C. S.; Ribeiro, Ligia N. M.; Darder, Margarita; Ruiz-Hitzky, Eduardo
The objective of the present study is to develop colon targeted drugdeliverysystems for mebendazole using guar gum as a carrier. Matrix tablets containing various proportions of guar gum were prepared by wet granulation technique using starch paste as a binder. The tablets were evaluated for drug content uniformity, and were subjected to in vitro drug release studies. The amount of mebendazole released from the matrix tablets at different time intervals was estimated by a high-performance liquid chromatography method. Guar gum matrix tablets released 8-15% of the mebendazole in the physiological environment of stomach and small intestine depending on the proportion of guar gum used in the formulation. When the dissolution study was continued in simulated colonic fluids the matrix tablets containing 20% of guar gum released another 83% of mebendazole after degradation into 2-3 pieces. The matrix tablets containing 30% of guar gum also released about 50% of mebendazole in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that matrix tablets containing either 20% or 30% of guar gum are most likely to provide targeting of mebendazole for local action in the colon. The mebendazole matrix tablets containing either 20% or 30% of guar gum showed no change either in physical appearance, drug content or dissolution pattern after storage at 45 degrees C/75% relative humidity for 3 months. Differential scanning calorimetry indicated no possibility of interaction between mebendazole and guar gum. PMID:11689262
Krishnaiah, Y S; Veer Raju, P; Dinesh Kumar, B; Bhaskar, P; Satyanarayana, V
Many biodegradable polymers were used for drugdelivery and some are successful for human application. There remains fabrication problems, such as difficult processability and limited organic solvent and irreproducible drug release kinetics. New star-shaped block copolymers, of which the typical molecular architecture is presented, results from their distinct solution properties, thermal properties and morphology. Their unique physical properties are due
B. Jeong; Y. K. Choi; Y. H. Bae; G. Zentner; S. W. Kim
Drugdeliverysystems incorporated onto the end of cardiac leads are used to reduce inflammation and fibrosis at the lead-tissue interface and enable optimal lead performance. In this research, confocal Raman microscopy was used to capture chemical images of the drugdeliverysystem on pacemaker leads in different elution media in real-time. Raman images in ambient air showed that drug
The goal of this research project was to develop a novel targeted drugdeliverysystem which would allow delivery of drugs directly to cancerous breast tissue without delivering significant amounts of drug to other parts of the body. The systems described...
In order to achieve a zero-order release of protein drugs, we have developed a new drugdeliverysystem using silicone, which is named the covered-rod-type formulation. Preparation of the covered-rod-type formulation was conducted under mild conditions without heat treatment or the use of organic solvents. The covered-rod-type formulation released human serum albumin (HSA) or interferon (IFN) at a constant rate
Since ancient times, chemopreventive agents have been used to treat/prevent several diseases including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, antioxidant, antiproliferative, anticarcinogenic, and antiangiogenic activity in various cell cultures and some animal studies. Research over the past 4 decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drugdeliverysystems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been shown to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician's armamentarium. PMID:21546540
From ancient times, chemopreventive agents have been used to treat/prevent several diseases, including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, anti-oxidant, anti-proliferative, anti-carcinogenic, and anti-angiogenic activity in various cell culture and some animal studies. Research over the past four decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell-culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drugdeliverysystems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been demonstrated to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician’s armamentarium.
The purpose of this study was to explore the application of low-density ion exchange resin (IER) Tulsion(R) 344, for floating drugdeliverysystem (FDDS), and study the effect of its particle size on rate of complexation, water uptake, drug release, and in situ complex formation. Batch method was used for the preparation of complexes, which were characterized by physical methods. Tablet containing resin with high degree of crosslinking showed buoyancy lag time (BLT) of 5-8 min. Decreasing the particle size of resin showed decrease in water uptake and drug release, with no significant effect on the rate of complexation and in situ complex formation for both preformed complexes (PCs) and physical mixtures (PMs). Thus, low-density and high degree of crosslinking of resin and water uptake may be the governing factor for controlling the initial release of tablet containing PMs but not in situ complex formation. However, further sustained release may be due to in situ complex formation. PMID:18777244
A conceptually novel periodontal drugdeliverysystem (DDS) is described that is intended for treatment of microbial infections associated with periodontitis. The DDS is a composite wafer with surface layers possessing adhesive properties, while the bulk layer consists of antimicrobial agents, biodegradable polymers, and matrix polymers. The wafers contain poly(lactic-co-glycolic acid) as the main bioerodible component used in the bulk layer and ethyl cellulose applied as a matrix polymer enabling diffusion-controlled release. Starch and other polymers in combination with AgNO(3) serve as coatings adhesive to the teeth. In vitro experiments demonstrate that the wafers are capable of zero-order release of antimicrobial agents such as silver nitrate, benzylpenicillin, and tetracycline, for over 4 weeks. PMID:11295218
In order to solve the problems of the side effects and medical lowering, has been advanced a study on the drugdeliverysystem (DDS) to accumulate the drugs locally in the body with minimum dosage. The DDS is a system that controls the drug kinetics in the body precisely and accumulates the drug locally at the target part, keeping the drugs at high density. Among the DDS, the magnetic drugdeliverysystem (MDDS) is the one that we studied. This is a technique to accumulate drugs by using the magnetic force as the physical driving force. Our previous researches showed the possibility of the technique of MDDS to accumulate the drugs with higher accumulation rate and locality than the traditional methods. It is necessary to apply a strong external magnetic field and a high magnetic gradient to accumulate the ferromagnetic drugs at a deep diseased part non-invasively. However, by applying a static magnetic field from one direction, the drug accumulates only at the surface of the body locates near the magnet. In this study, we tried to change the magnetic field applied by a superconducting bulk magnet with time, in order to make a constant and strong magnetic field applied in the center of the body and to accumulate the ferromagnetic drugs at the deep target part in the body.First of all, the effect of the surface treatment of the ferromagnetic drugs to prevent its absorption in the normal tissue was examined. Then, to increase the accumulation rate of the ferromagnetic drugs at the target part, the distribution of magnetic field was changed, and the optimum spatial and temporal conditions of magnetic field were examined.
Chuzawa, M.; Mishima, F.; Akiyama, Y.; Nishijima, S.
Lipid based drugdeliverysystems, and in particular self-emulsifying drugdeliverysystems (SEDDS), show great potential for enhancing oral bioavailability but have not been broadly applied, largely due to lack of general formulation guidance. To help understand how formulation design influences physicochemical emulsion properties and associated function in the gastrointestinal environment, a range of twenty-seven representative self-emulsifying formulations were investigated. Two key functions of emulsion-based drugdeliverysystems, permeability enhancement and drug release, were studied and statistically related to three formulation properties - oil structure, surfactant hydrophilic liphophilic balance (HLB) values, and surfactant-to-oil ratio. Three surfactants with HLB values ranging from 10 to 15 and three structurally different oils (long chain triglyceride, medium chain triglyceride, and propylene glycol dicaprylate/dicaprate) were combined at three different weight ratios (1:1, 5:1, 9:1). Unstable formulations of low HLB surfactant (HLB=10) had a toxic effect on cells at high (1:1) surfactant concentrations, indicating the importance of formulation stability for minimizing toxicity. Results also indicate that high HLB surfactant (Tween 80) loosens tight junction at high (1:1) surfactant concentrations. Release coefficients for each emulsion system were calculated. Incorporation of a long chain triglyceride (Soybean oil) as the oil phase increased the drug release rate constant. These results help establish an initial foundation for relating emulsion function to formulation design and enabling bioavailability optimization across a broad, representative range of SEDDS formulations. PMID:19850092
Buyukozturk, Fulden; Benneyan, James C; Carrier, Rebecca L
Formulation of poorly soluble drugs is a general intractable problem in pharmaceutical field, especially those compounds poorly\\u000a soluble in both aqueous and organic media. It is difficult to resolve this problem using conventional formulation approaches,\\u000a so many drugs are abandoned early in discovery. Nanocrystals, a new carrier-free colloidal drugdeliverysystem with a particle\\u000a size ranging from 100 to 1000 nm,
To develop a self-nanoemulsifying drugdeliverysystem (SNEDDS) for protein drugs, and particularly, to test the in vitro transport of beta-lactamase (BLM) by SNEDDS across the cell monolayer. Fluorescently labeled BLM (FITC-BLM), a model protein, formulated into 16 SNEDDS preparations through a solid dispersion technique were studied for transport across MDCK monolayer. All the SNEDDS nanoemulsions resulted in higher transport rate than the free solution. The transport rate by SNEDDS depends on the SNEDDS composition. SNEDDS NE-12-7 (oil: Lauroglycol FCC, surfactant: Cremophor EL and a cosurfactant: Transcutol HP) at the ratio of 5:4:3, rendered the highest transportation rate, 33% as compared to negligible transport by the free solution. FITC-BLM solution mixed with the surfactant and the cosurfactant of SNEDDS NE-12-7 or with blank SNEDDS NE-12-7 increased the transport only by 3.3 and 1.5 folds, respectively, compared to free solution alone. It was found that the monolayer integrity was not compromised in the presence of SNEDDS NE-12-7 or its surfactant/cosurfactant. The SNEDDS significantly increased the transport of FITC-BLM across MDCK monolayer in vitro. SNEDDS may be a potential effective deliverysystem for non-invasive protein drugdelivery. PMID:18640797
Rao, Sripriya Venkata Ramana; Agarwal, Payal; Shao, Jun
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
Gold nanoparticles (AuNPs) are a suitable platform for development of efficient deliverysystems. AuNPs can be easily synthesized, functionalized, and are biocompatible. The tunability of the AuNP monolayer allows for complete control of surface properties for targeting and stability/release using these nanocarriers. This review will discuss several delivery strategies utilizing AuNPs.
Duncan, Bradley; Kim, Chaekyu; Rotello, Vincent M.
\\u000a Local drugdelivery to the eye minimizes systemic side effects and targets specific ocular tissue. In preclinical studies,\\u000a transscleral and suprachoroidal delivery appear to achieve therapeutic drug tissue levels that target specific tissues, such\\u000a as the choroid and macula. These routes allow minimally invasive sustained delivery of drugs to the ocular posterior segment\\u000a while minimizing systemicdrug levels and the
As a novel targeting drugdeliverysystem, acid-sensitive micelles have many advantages, such as increasing solubility of lipophilic drugs, acid-sensitive release, high drug loading, etc. They can load drugs though non-covalent encapsulation and covalent conjugation methods. In tumor tissues, drugs are released quickly from the depolymerized micelles with lipophilic copolymer protonation or lypohydrophilic copolymer hydrolysis and covalent conjugated drugs are released when the acid-sensitive covalent linkage breaks. This review mainly advances acid-sensitive micelles for the tumor targeting drugdeliverysystems from drug-loaded methods and release mechanisms. PMID:22799024
Although preformed polymers are commercially available for use in the design and development of drugdeliverysystems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drugdelivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drugdelivery and the possibilities it provides to overcome the challenges of oral route of administration.
Skin as an important site of drug application for both local and systemic effects. However in skin, the stratum corneum is the main barrier for drug penetration. Penetration enhancement technology is a challenging development that would increase the number of drugs available for transdermal administration. The permeation of drug through skin can be enhanced by both chemical penetration enhancement and
An innovative drugdeliverysystem based on magnetic and fluorescent multifunctional chitosan nanoparticles was developed, which combined magnetic targeting, fluorescent imaging and stimulus-responsive drug release properties into one drugdeliverysystem. Water-soluble superparamagnetic Fe3O4 nanoparticles, CdTe quantum dots (QDs) and pharmaceutical drugs were simultaneously incorporated into chitosan nanoparticles; cross-linking the composite particles with glutaraldehyde tailored their size, morphology, surface properties
Linlin Li; Dong Chen; Yanqi Zhang; Zhengtao Deng; Xiangling Ren; Xianwei Meng; Fangqiong Tang; Jun Ren; Lin Zhang
A multifunctional drugdeliverysystem based on hydroxypropyl methylcellulose (HPMC)-matrices (tablets) placed within an impermeable polymeric cylinder (open at both ends) was developed. Depending on the configuration of the device, extended release, floating or pulsatile drugdeliverysystems could be obtained. The release behaviour of the different devices was investigated as a function of HPMC viscosity grade, HPMC content, type
Membrane permeation-controlled transdermal drugdeliverysystems were prepared using the natural polymer, chitosan. An adhesive sealing technique was used to construct the devices. Propranolol hydrochloride was selected as the model drug for the present study. Chitosan membranes with different permeability to propranolol hydrochloride obtained by controlled cross-linking with glutaraldehyde were used to regulate the drug release in the devices. Chitosan
Present work provides an overall study about the types and the medicinal treatment of the rheumatic diseases especially the intraarticular formulations. Due to the localized nature of the joint, intraarticular injections are very favourable drugdeliverysystems. It has a big advantage over the oral medication; the systemic side effects are kept away. The review shows two types of the rheumatic diseases on the example of the healthy joint: the joint damage (osteoarthritis) and the inflamed joint (rheumatoid arthritis). There are many active ingredients for the treatment of the rheumatic diseases but the number of the intraarticular products is limited. At present are only formulations with hyaluronic acid or glucocorticoid on the market. Several physiological and biopharmaceutical aspects must be considered for the design of intraarticular injections. During and after the production many quality requirements have to be complied. On the market the formulations in solution or in suspension are available, which provide a short-term effect. The aim of the developments is to achieve long-term effect based on nano- or microparticles. PMID:21800713
Background: This project aims to formulate and characterize a drug-eluting contact lens to provide controlled release of drug for a longer period of time, using liposomes as drugdeliverysystem. Materials and Methods: Drug delivering contact lenses were created by coating disposable soft contact lenses with ciprofloxacin entrapped in the liposomes. Reverse phase evaporation and lipid film hydration methods were used for the preparation of ciprofloxacin trapping reverse phase evaporation vesicles, that is, unilamellar vesicles (REVs) and multilamellar vesicles (MLVs), respectively. Soya lecithin and cholesterol (CH) were used in the molar ratios of 7:4 and 7:2. The spherical structure of the liposomes, the mean diameter, and their purity were determined by photomicroscopic, transmission electron microscope, and chromatographic analysis, respectively. The prepared liposomes were evaluated for their entrapment efficiency, in vitro drug release, stability, and toxicity. Results: MLVs were larger than REVs with their mean diameter 338.32 nm and also entrapped greater amount of ciprofloxacin. Drug loading and its release from the liposomal vesicles was dependent on CH content. Ciprofloxacin released from the liposomes coated on the contact lenses not only inhibited both Staphylococcus aureus and Pseudomonas aeruginosa on an agar plate but also showed an enhanced antibacterial effect as determined by minimal inhibitory concentrations. Approximately 40% of ciprofloxacin was retained up to a period of 3 months at 4°C. Furthermore, the formulation was found to be nontoxic and also a reduction in toxicity of ciprofloxacin was observed after entrapment when assessed by lymphocyte toxicity assay and chick embryo inoculation. Conclusions: An innovative drugdeliverysystem consisting of drug-loaded liposomes coated onto the surface of contact lenses has been developed. This system is highly specific in terms of localized and sustained application of the drug.
The research of radiation effects on drugs over the past 60 years has mainly dealt with radiation sterilization of individual active pharmaceutical ingredients (APIs) in the form of pure substances or injectable solutions. However, the emergence of novel systems for drug administration and targeting via controlled drugdelivery (CDD) and/or controlled drug release (CDR) has extended the use of irradiation with respect to pharmaceuticals: the capacity of radiation to act as an initiator of crosslinking has been used in the manufacturing and modification of a number of polymeric carriers with an added advantage of reducing the microbial load of products at the same time. The application of irradiation to these novel systems requires the understanding of radiation action not only on APIs alone but also on drug carriers and on the functioning of the integral CDD/CDR systems. In this paper, the significance of CDD/CDR systems is considered with a special emphasis on the role of irradiation for sterilization and crosslinking in the developments over the past 15 years. Radiation sterilization, crosslinking and degradation of the principal forms of drug carrier systems and the effects of irradiation on the release kinetics of APIs are discussed in light of radiation chemical principles. Regulatory aspects pertaining to radiation sterilization of drugs are also considered. Relevant results are summarized in tabular form.
Recent progress in understanding the molecular basis of cancer brought out new materials such as oligonucleotides, genes,\\u000a peptides and proteins as a source of new anticancer agents. Due to their macromolecular properties, however, new strategies\\u000a of delivery for them are required to achieve their full therapeutic efficacy in clinical setting. Development of improved\\u000a dosage forms of currently marketed anticancer drugs
In recent era various technologies have been made in research and development of controlled release oral drugdeliverysystem to overcome various physiological difficulties such as variation in gastric retention and emptying time. To overcome this drawback and to maximize the oral absorption of various drugs, novel drugdeliverysystems have been developed. Gastroretentive drugdeliverysystem is facing many challenges which can be overcome by upcoming newly emerging approach i.e. raft forming system. The purpose of writing this review is to focus on recent development of stomach specific floating drugdeliverysystem to circumvent the difficulties associated with formulation design. Various gastroretentive approaches that have been developed till now are also discussed. The present study provides valuable information & highlights advances in this raft forming system. This review attempts to discuss various factors like physiological factors, physicochemical factors and formulation factors to be considered in the development of the raft forming system. Different types of smart polymers used for their formulation have also been summarized. The review focuses on the mechanism, formulation and development of the raft forming system. This review also summarizes the studies to evaluate the performance and application of these systems. The study finally highlights advantages, disadvantages, and marketed preparation of the raft forming system. PMID:23500062
To use self-nanoemulsifying drugdeliverysystem (SNEDDS) to deliver hydrophilic proteins orally. beta-Lactamase (BLM), a 29 kDa protein was used as a model protein, and formulated into the oil phase of a SNEDDS through solid dispersion technique. The oral absorption of BLM in rats when delivered by such a SNEDDS was investigated. Oral delivery of 4500 mU/kg of BLM in SNEDDS nanoemulsion resulted in the relative bioavailability of 6.34%, C(max) of 1.9 mU/ml and mean residence time of 12.12h which was 1.5-, 2.7- and 1.3-fold higher than that by free solution, respectively. Delivery of BLM in the aqueous phase of the nanoemulsion resulted in a PK profile similar to that by the free solution. BLM when loaded in oil phase of SNEDDS, can significantly enhance the oral bioavailability of BLM. SNEDDS has a great potential for oral protein delivery. PMID:18650037
Rao, Sripriya Venkata Ramana; Yajurvedi, Kavya; Shao, Jun
Mixed micelles prepared using sodium taurocholate (TA) and egg lecithin (LE) were previously found to be an effective carrier for sustained release of a poorly water-soluble drug in transscleral iontophoretic delivery. The objectives of the present study were to investigate the effects of drug lipophilicity upon micellar carrier solubilization potential and drug release profiles from the sclera after iontophoretic delivery of model lipophilic drugs dexamethasone (DEX), triamcinolone acetonide (TRIAM), and ?-estradiol (E2?) with a mixed micellar carrier system of TA-LE (1:1 mole ratio). In this study, the micellar carrier system was characterized for drug solubilization. The micelles encapsulating these drugs were evaluated for transscleral passive and 2-mA iontophoretic delivery (both cathodal and anodal) and drug release from excised human sclera in vitro. The results show that drug solubility enhancement of the micellar carrier system increased with increasing drug lipophilicity. The more lipophilic drugs E2? and TRIAM displayed slower drug release from the sclera compared with the less lipophilic drug DEX after iontophoretic drugdelivery with the mixed micelles. These results suggest that the combination of transscleral iontophoresis and micellar carriers is more effective in sustaining transscleral delivery of the more lipophilic drugs studied in this investigation. PMID:23150488
Background and Aim: Telmisartan (TEL) is an angiotensin II receptor blocker (ARB) antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drugdeliverysystem (SNEDDS) to enhance the oral bioavailability of poorly water soluble TEL. Materials and Methods: The solubility of TEL in various oils was determined to identify the oil phase of a SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsifying region. A SNEDDS was further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, dilution, droplet size, zeta potential, pH, refractive index, and viscosity. Results: The developed SNEDDS formulation contained TEL (20 mg), Tween® 20 (43.33%w/w), Carbitol® (21.67%w/w), and Acrysol® EL 135 (32%w/w). The optimized formulation of the TEL-loaded SNEDDS exhibited a complete in vitro drug release in 15 min as compared with the plain drug, which had a limited dissolution rate. It was also compared with the pure drug suspension by oral administration in male Wister rats. The in vivo study exhibited a 7.5-fold increase in the oral bioavailability of TEL from the SNEDDS compared with the pure drug suspension. Conclusions: These results suggest the potential use of the SNEDDS to improve the dissolution and oral bioavailability of poorly water soluble TEL.
To aim directly at the research status of Chinese drugs pharmaceutics, this study provides a new research idea "traditional Chinese medicine multiple drugdeliverysystem based on material basis component". This thought according to whole concept, syndrome, and Chinese medicine characteristics of multi-component, multi-target, multi-effect. The premise of designing traditional Chinese medicine multiple drugdeliverysystem is material basis component, and the purpose is to improve bioavailability. The example of multi-drugdeliverysystem of tongmai micro-pellets is expounded for application. This new research model of Chinese drugs pharmaceutics provides new strategies and methods for the development of modern Chinese drugdeliverysystems. PMID:23126211
An innovative drugdeliverysystem based on magnetic and fluorescent multifunctional chitosan nanoparticles was developed, which combined magnetic targeting, fluorescent imaging and stimulus-responsive drug release properties into one drugdeliverysystem. Water-soluble superparamagnetic Fe3O4 nanoparticles, CdTe quantum dots (QDs) and pharmaceutical drugs were simultaneously incorporated into chitosan nanoparticles; cross-linking the composite particles with glutaraldehyde tailored their size, morphology, surface properties and drug release behaviors. The system showed superparamagnetic and strong fluorescent properties, and was used as a controlled drug release vehicle, which showed pH-sensitive drug release over a long time. The composite magnetic and fluorescent chitosan nanoparticles are potential candidates as a smart drugdeliverysystem.
Shape memory alloy actuators feature an extremely high power-to-volume ratio. This property is a major advantage for miniature applications. This paper describes implantable drug-deliverysystems based on shape memory alloy micro-actuation. A first type is designed for use with solid drugs while a second design enables delivery of liquid drugs. The operating principle of the latter system is based on
Dominiek Reynaerts; Jan Peirs; Hendrik Van Brussel
Drug release by diffusion from an unstressed thin polymer film with a dissolved crystallizable component was simulated using a kinetic Monte Carlo model. This model was used previously to study Ostwald ripening in a high crystallizable component regime and was shown to correctly simulate solvation, diffusion, and precipitation. In this study, the same model with modifications was applied to the drug transportation and release in the low concentration regime of interest to the transdermal drugdeliverysystem (TDS) community. We demonstrate the model's utility by simulating diffusion, crystal precipitation, growth and shrinkage during storage, and drug release from the thin TDS to a surface under different conditions. The simulation results provide a first approximation for the drug release profile occurring from TDS to skin. It has been reported that growth of drug crystals in TDS occurs mainly in the middle third of the polymer layer at relatively higher temperatures. The results from the simulations showed that the release rate and concentration profile of a TDS depend on the dissolution process of the crystal. At low storage temperature, the drug precipitates to form small evenly distributed crystals throughout the thickness of the TDS patch. The release rate of these small, evenly distributed crystals most closely matched that of a completely dissolved drug. PMID:16430302
Introduction Nanocapsules, existing in miniscule size, range from 10 nm to 1000 nm. They consist of a liquid/solid core in which the drug is placed into a cavity, which is surrounded by a distinctive polymer membrane made up of natural or synthetic polymers. They have attracted great interest, because of the protective coating, which are usually pyrophoric and easily oxidized and delay the release of active ingredients. Methods Various technical approaches are utilized for obtaining the nanocapsules; however, the methods of interfacial polymerization for monomer and the nano-deposition for preformed polymer are chiefly preferred. Most important characteristics in their preparation is particle size and size distribution which can be evaluated by using various techniques like X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolu¬tion transmission electron microscopy, X-ray photoelectron spectroscopy, superconducting quantum interference device, multi angle laser light scattering and other spectroscopic techniques. Results Nanocapsules possessing extremely high reproducibility have a broad range of life science applications. They may be applied in agrochemicals, genetic engineering, cosmetics, cleansing products, wastewater treatments, adhesive component applications, strategic delivery of the drug in tumors, nanocapsule bandages to fight infec¬tion, in radiotherapy and as liposomal nanocapsules in food science and agriculture. In addition, they can act as self-healing materials. Conclusion The enhanced delivery of bio¬active molecules through the targeted delivery by means of a nanocapsule opens numerous challenges and opportunities for the research and future development of novel improved therapies.
The colon is a site where both local and systemicdelivery of drugs can take place. Local delivery allows topical treatment of inflammatory bowel disease. However, treatment can be made effective if the drugs can be targeted directly into the colon, thereby reducing the systemic side effects. This review, mainly compares the primary approaches for CDDS (Colon Specific DrugDelivery) namely prodrugs, pH and time dependent systems, and microbially triggered systems, which achieved limited success and had limitations as compared with newer CDDS namely pressure controlled colonic delivery capsules, CODESTM, and osmotic controlled drugdelivery which are unique in terms of achieving in vivo site specificity, and feasibility of manufacturing process. PMID:22125706
The unique photophysical properties of noble metal nanoparticles contribute to their potential as photoactivated drugdelivery vectors. Here we demonstrate the synthesis and characterization of 60-80 nm silver nanoparticles (SNPs) decorated with thiol-terminated photolabile DNA oligonucleotides. In vitro assays and fluorescent confocal microscopy of treated cell cultures show efficient UV-wavelength photoactivation of surface-tethered caged ISIS2302 antisense oligonucleotides possessing internal photocleavable linkers. As a demonstration of the advantages of these novel nanocarriers, we investigate properties including: enhanced stability to nucleases, increased hybridization activity upon photorelease, and efficient cellular uptake as compared to commercial transfection vectors. Their potential as multicomponent delivery agents for oligonucleotide therapeutics is shown through regulation of ICAM-1 (Intracellular Adhesion Molecule-1) silencing. Our results suggest a means to achieve light-triggered, spatiotemporally controlled gene silencing via nontoxic silver nanocarriers, which hold promise as tailorable platforms for nanomedicine, gene expression studies, and genetic therapies. PMID:23473419
Brown, Paige K; Qureshi, Ammar T; Moll, Alyson N; Hayes, Daniel J; Monroe, W Todd
The great challenge in using native degradable polysaccharides for the development of drugdeliverysystems is their high aqueous solubility, which may contribute to the undesirable premature and localized release of the drug. Multiparticulate systems showing simultaneously specific biodegradability and pH-dependent drug release were prepared based on chitosan (CS), amidated pectin (PC), and calcium ions, using triamcinolone (TC) as model
Giselle F. Oliveira; Priscileila C. Ferrari; Lívia Q. Carvalho; Raul C. Evangelista
Purpose: The aim of the study was to develop a proniosomal carrier system for captopril for the treatment of hypertension that is capable of efficiently delivering entrapped drug over an extended period of time. Method: The potential of proniosomes as a transdermal drugdeliverysystem for captopril was investigated by encapsulating the drug in various formulations of proniosomal gel composed
The objective of investigation was to prepare nanoemulsion containing risperidone (RSP) to accomplish the delivery of drug to the brain via nose. Risperidone nanoemulsion (RNE) and mucoadhesive nanoemulsion (RMNE) were characterized for drug content, pH, percentage transmittance, globule size and zeta potential. Biodistribution of RNE, RMNE, and risperidone solution (RS) in the brain and blood of Swiss albino rats following intranasal (i.n.) and intravenous (i.v.) administration was examined using optimized technetium labeled ((99m)Tc-labeled) RSP formulations. Gamma scintigraphy imaging of rat brain following i.v. and i.n. administrations were performed to ascertain the localization of drug in brain. The brain/blood uptake ratio of 0.617, 0.754, 0.948, and 0.054 for RS (i.n.), RNE (i.n.), RMNE (i.n.), and RNE (i.v.), respectively, at 0.5h are indicative of direct nose to brain transport bypassing the blood-brain barrier. Higher drug transport efficiency (DTE%) and direct nose to brain drug transport (direct transport percentage, DTP%) for mucoadhesive nanoemulsions indicated more effective and best brain targeting of RSP amongst the prepared nanoemulsions. Studies conclusively demonstrated rapid and larger extent of transport of RSP by RMNE (i.n.) when compared to RS (i.n.), RNE (i.n.) and RNE (i.v.) into the rat brain. PMID:18455333
Kumar, Mukesh; Misra, Ambikanandan; Babbar, A K; Mishra, A K; Mishra, Puspa; Pathak, Kamla
A variety of ocular drugdeliverysystems, including a controlled release of the drug, drug targeting, and penetration enhancement of the drug, have been investigated. Biodegradable polymers have been widely used as the drug carrier for controlled-release systems. Biodegradable polymers release the drug as they themselves degrade and are finally absorbed within the body. Several ocular drugdeliverysystems using
The synthesis of two water soluble dendrimers is described. The formation of water soluble inclusion complexes with a variety of small, hydrophobic guest molecules is also described. Moreover, when these guest molecules are drug moieties, then the resulting drug\\/dendrimer complexes can be considered ideal candidates for use as novel drugdeliverysystems.
Lance J. Twyman; Anthony E. Beezer; R. Esfand; Martin J. Hardy; John C. Mitchell
The monolithic matrix type transdermal drugdeliverysystems of pinacidil monohydrate (PM) were prepared by film casting technique on mercury substrate and characterised in vitro by drug release studies using paddle over disc assembly, skin permeation studies using Keshary and Chein diffusion cell on albino rat skin and drug-excipient interaction analysis. Four formulations were developed which differed in the ratio
The results of experimental studies concerned with the development of nano-sized drugdeliverysystems for the antitumour drugs sarcolysine and melphalan are generalized. The structures and biological activities of nanocarriers in comparison with unmodified drugs are discussed. Particular attention is given to the liposomes containing lipid derivatives of sarcolysine and melphalan in the lipid bilayer. The bibliography includes 196 references.
Krasnov, V. P.; Korolyova, M. A.; Vodovozova, E. L.
Electrospinning and fluorination were carried out in order to obtain a controlled release drugdeliverysystem to solve the problem of both an initial burst of the drug and a limited release time. Poly(vinyl alcohol) was electrospun with Procion Blue as a model drug and heat treated in order to obtain cross-linked hydrogel fibers. Two different kinds of electrospun fibers
Ji Sun Im; Jumi Yun; Youn-Mook Lim; Hyung-Il Kim; Young-Seak Lee
Poor efficacy and off-target systemic toxicity are major problems associated with current chemotherapeutic approaches to treat cancer. We developed a new form of polyvalent therapeutics that is composed of multiple aptamer units synthesized by rolling circle amplification and physically intercalated chemotherapy agents (termed as "Poly-Aptamer-Drug"). Using a leukemia cell-binding aptamer and doxorubicin as a model system, we have successfully constructed Poly-Aptamer-Drugsystems and demonstrated that the Poly-Aptamer-Drug is significantly more effective than its monovalent counterpart in targeting and killing leukemia cells due to enhanced binding affinity (?40 fold greater) and cell internalization via multivalent effects. We anticipate that our Poly-Aptamer-Drug approach will yield new classes of tunable therapeutics that can be utilized to effectively target and treat cancers while minimizing the side effects of chemotherapy. PMID:24044994
Zhang, Zhiqing; Ali, M Monsur; Eckert, Mark A; Kang, Dong-Ku; Chen, Yih Yang; Sender, Leonard S; Fruman, David A; Zhao, Weian
Bioadhesive superporous hydrogel composite (SPHC) particles were developed for an intestinal delivery of metoprolol succinate and characterized for density, porosity, swelling, morphology, and bioadhesion studies. Chitosan and HPMC were used as bioadhesive and release retardant polymers, respectively. A 32 full factorial design was applied to optimize the concentration of chitosan and HPMC. The drug loaded bioadhesive SPHC particles were filled in capsule, and the capsule was coated with cellulose acetate phthalate and evaluated for drug content, in vitro drug release, and stability studies. To ascertain the drug release kinetics, the drug release profiles were fitted for mathematical models. The prepared system remains bioadhesive up to eight hours in intestine and showed Hixson-Crowell release with anomalous nonfickian type of drug transport. The application of SPHC polymer particles as a biomaterial carrier opens a new insight into bioadhesive drugdeliverysystem and could be a future platform for other molecules for intestinal delivery.
Bioadhesive superporous hydrogel composite (SPHC) particles were developed for an intestinal delivery of metoprolol succinate and characterized for density, porosity, swelling, morphology, and bioadhesion studies. Chitosan and HPMC were used as bioadhesive and release retardant polymers, respectively. A 3(2) full factorial design was applied to optimize the concentration of chitosan and HPMC. The drug loaded bioadhesive SPHC particles were filled in capsule, and the capsule was coated with cellulose acetate phthalate and evaluated for drug content, in vitro drug release, and stability studies. To ascertain the drug release kinetics, the drug release profiles were fitted for mathematical models. The prepared system remains bioadhesive up to eight hours in intestine and showed Hixson-Crowell release with anomalous nonfickian type of drug transport. The application of SPHC polymer particles as a biomaterial carrier opens a new insight into bioadhesive drugdeliverysystem and could be a future platform for other molecules for intestinal delivery. PMID:23984380
A novel colon targeted tablet formulation was developed using pectin as carrier and diltiazem HCl and indomethacin as model drugs. The tablets were coated with inulin followed by shellac and were evaluated for average weight, hardness and coat thickness. In vitro release studies for prepared tablets were carried out for 2 h in pH 1.2 HCl buffer, 3 h in pH 7.4 phosphate buffer and 6 h in simulated colonic fluid. The drug release from the coated systems was monitored using UV/Vis spectroscopy. In vitro studies revealed that the tablets coated with inulin and shellac have limited the drug release in stomach and small intestinal environment and released maximum amount of drug in the colonic environment. The study revealed that polysaccharides as carriers and inulin and shellac as a coating material can be used effectively for colon targeting of both water soluble and insoluble drugs. PMID:20390095
A novel colon targeted tablet formulation was developed using pectin as carrier and diltiazem HCl and indomethacin as model drugs. The tablets were coated with inulin followed by shellac and were evaluated for average weight, hardness and coat thickness. In vitro release studies for prepared tablets were carried out for 2 h in pH 1.2 HCl buffer, 3 h in pH 7.4 phosphate buffer and 6 h in simulated colonic fluid. The drug release from the coated systems was monitored using UV/Vis spectroscopy. In vitro studies revealed that the tablets coated with inulin and shellac have limited the drug release in stomach and small intestinal environment and released maximum amount of drug in the colonic environment. The study revealed that polysaccharides as carriers and inulin and shellac as a coating material can be used effectively for colon targeting of both water soluble and insoluble drugs.
Inorganic-based deliverysystems are attracting increased attention partially because their inertness gives rise to safety\\u000a and stability in biosystems and partially because their frameworks can be readily and exactly manipulated. Among the diverse\\u000a inorganic candidates, such as nanoparticles and clays, we have focused our attention on layered double hydroxides (LDH) with\\u000a anion-exchange capacity. Diverse anionic molecules can be loaded into
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 drugdelivery 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 drugdelivery based on natural polysaccharides has highly been acclaimed in recent years. A colon specific drugdeliverysystem 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 drugdelivery in terms of target specificity. PMID:24032514
In this paper, we develop a direct adaptive control framework for uncertain linear compartmental dynamical systems with actuator amplitude constraints and system time delays. The specific focus of the paper is on compartmental pharmacokinetic models and their applications to drugdeliverysystems. In particular, we develop a Lyapunov-Krasovskiibased direct adaptive control framework for guaranteeing set-point regulation of the closed-loop system
Qing Hui; Wassim M. Haddad; VijaySekhar Chellaboina; T. Hayakawa
Abstract Context: Ritonavir (RTV) is a human immunodeficiency virus (HIV) protease inhibitor (PI) with activity against HIV, practically insoluble in water and recommended to co-administer as a booster along with other HIV-PI to enhance their bioavailability. The present study is aimed to enhance the dissolution and oral bioavailability of water-insoluble RTV using the Solid Self-Microemulsifying DrugDeliverySystem (S-SMEDDS). Objective: To enhance the dissolution and oral bioavailability of water-insoluble RTV using the S-SMEDDS. Material and methods: Liquid SMEDDS (L-SMEDDS) of RTV was formulated by the optimizing ratio of Imwitor 988 (Oil), Cremophor EL and Cremophor RH 40 (1:1) (surfactant) and Capmul GMS K-50 (cosurfactant). Optimized L-SMEDDS showed improved dissolution rate of RTV compared to pure RTV powder. Optimized L-SMEDDS of RTV was adsorbed on Neusilin US-2 using a simple wet granulation technique with selected excipients to convert it into S-SMEDDS. Results and discussion: Optimized L-SMEDDS showed an improved dissolution rate of RTV compared to pure RTV powder. Droplet size of resultant microemulsion of L-SMEDDS of RTV was observed between 16 and 22 nm and independent of pH (i.e. 0.1 N HCl and water). Conversion of the crystalline form of RTV to amorphous form was observed when RTV formulated into SMEDDS form as per X-ray diffraction study. In vitro dissolution study, stability study of optimized S-SMEDDS confirmed the formulation of stable and improved dissolution of RTV. Relative bioavailability of RTV was determined in male Wistar rats and pharmacokinetic parameters were calculated by the comparison of optimized S-SMEDDS versus aqueous suspension of RTV. S-SMEDDS improved the plasma profile in terms of maximum plasma concentration (Cmax), and area under curve (AUC0-24h), which is almost twofolds higher than the aqueous suspension of RTV. Conclusion: S-SMEDDS tablet of RTV was formulated successfully by adsorbing optimized L-SMEDDS of RTV on Neusilin-US2® as a potential carrier with enhanced solubility and relative oral bioavailability compared to pure RTV by twofolds. PMID:23465049
The authors describe a radionuclide technique for evaluating intrathecal and intraventricular infusions by surgically implanted drug pump deliverysystems. Sixteen patients underwent flow studies, performed by injecting 500 mu Ci of indium-111 DTPA into the pumps. Early and delayed images were obtained. These studies enabled distinction among functioning pumps, nonfunctioning pumps, and obstructed or occluded catheters. We conclude that indium-111 DTPA flow studies provide an excellent way to assess these drug pump deliverysystems.
The objectives of this study were to develop and evaluate a novel self-emulsifying floating drugdeliverysystem (SEFDDS)\\u000a that resulted in improved solubility, dissolution, and controlled release of the poorly water-soluble tetrahydrocurcumin (THC).\\u000a The formulations of liquid self-emulsifying drugdeliverysystem (SEDDS; mixtures of Labrasol, Cremophor EL, Capryol 90, Labrafac\\u000a PG) were optimized by solubility assay and pseudo-ternary phase diagram
Conventional pharmacokinetic methods for studying ocular drugdelivery 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-deliverysystems 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 drugdelivery 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 drugdelivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed.
Hydrophobicity has been an obstacle that hinders the use of many anticancer drugs. A critical challenge for cancer therapy concerns the limited availability of effective biocompatible deliverysystems for most hydrophobic therapeutic anticancer drugs. In this study, we have developed a targeted near-infrared (NIR)-regulated hydrophobic drug-delivery platform based on gold nanorods incorporated within a mesoporous silica framework (AuMPs). Upon application of NIR light, the photothermal effect of the gold nanorods leads to a rapid rise in the local temperature, thus resulting in the release of the entrapped drug molecules. By integrating chemotherapy and photothermotherapy into one system, we have studied the therapeutic effects of camptothecin-loaded AuMP-polyethylene glycol-folic acid nanocarrier. Results revealed a synergistic effect in vitro and in vivo, which would make it possible to enhance the therapeutic effect of hydrophobic drugs and decrease drug side effects. Studies have shown the feasibility of using this nanocarrier as a targeted and noninvasive remote-controlled hydrophobic drug-deliverysystem with high spatial/temperal resolution. Owing to these advantages, we envision that this NIR-controlled, targeted drug-delivery method would promote the development of high-performance hydrophobic anticancer drug-deliverysystem in future clinical applications. PMID:23765904
The field of DNA nanotechnology has progressed rapidly in recent years and hence a large variety of 1D-, 2D- and 3D DNA nanostructures with various sizes, geometries and shapes is readily accessible. DNA-based nanoobjects are fabricated by straight forward design and self-assembly processes allowing the exact positioning of functional moieties and the integration of other materials. At the same time some of these nanosystems are characterized by a low toxicity profile. As a consequence, the use of these architectures in a biomedical context has been explored. In this review the progress and possibilities of pristine nucleic acid nanostructures and DNA hybrid materials for drugdelivery will be discussed. For the latter class of structures, a distinction is made between carriers with an inorganic core composed of gold or silica and amphiphilic DNA block copolymers that exhibit a soft hydrophobic interior. PMID:23742878
de Vries, Jan Willem; Zhang, Feng; Herrmann, Andreas
The poor water solubility of drugs is major problem for drug formulation. To date, nanoscale systems for drugdelivery have gained much interest as a way to improve the solubility problems. The reduction of drug particles into the sub-micron range leads to a significant increase in the dissolution rate and therefore enhances bioavailability. Nanosuspensions are promising candidates that can be
A mucoadhesive drug-deliverysystem (AmDDS) was developed using carbopol 934P to achieve dual-controlled delivery of N-9 and EDTA for enhanced fertility control. The effects of mucoadhesive polymers and calcium-related interaction on the residence characteristics of AmDDS within the vagina and the release kinetic profile of N-9 from AmDDS were investigated. Maximum adhesion force and work of adhesion shear derived from
Unlike controlled release systems that deliver a single drug, dual or multidrug deliverysystems with distinct release profiles are more likely to promote timely and effective tissue regeneration as they provide both temporally and concentration-dependent release of different molecules to mimic natural biological events. In this study, an injectable and biodegradable deliverysystem was developed to sequentially release an antiresorptive drug (clodronate) followed by an osteogenic agent (simvastatin) to treat bone disease. The injectable deliverysystem comprised simvastatin-loaded gelatin microspheres suspended in a viscous solution of carboxymethylcellulose (CMC) containing clodronate. Several factors (CMC concentration, glutaraldehyde concentration, simvastatin loading, and gelatin microsphere processing conditions) were investigated for their effects on drug release. Clodronate release was not affected by CMC concentration, with complete delivery within 12 hr, and simvastatin release could be modulated by cross-linking of the gelatin microspheres, loading, and washing conditions. Burst release of simvastatin was reduced from 70% to 6% in conjunction with sustained release for up to 3 weeks. The combined system showed early release of the antiresorptive clodronate sequentially followed by sustained delivery of the osteogenic simvastatin. This robust and flexible two-phase deliverysystem may prove useful for applications in which multiple drugdelivery is desired. PMID:22102375
Zou, Y; Brooks, J L; Talwalkar, V; Milbrandt, T A; Puleo, D A
Living organisms follow a circadian rhythm in which physiological processes such as hormonal secretion, metabolism, heart rate, and renal output are affected by the time of day. Chronotherapy coordinates drugdelivery with the circadian rhythm to enhance effectiveness and mitigate adverse effects and is achieved by delivering a drug when the system is most susceptible. Cancer is a chronotherapeutic disorder. Cancer treatment requires high doses of intravenous medication to kill cancerous cells; however, normal cells are also killed, creating intolerable side effects. This review shows that chronotherapy can play a vital role in the quality of life and survival rate for oncology patients. PMID:22955155
Librodo, Paul; Buckley, Mitchell; Luk, Marilyn; Bisso, Andrea
Oral colon-targeted drugdeliverysystems have gained enormous attention among researchers in the last two decades. The significance of this site-specific drugdeliverysystem can be measured by its usefulness for delivering a variety of therapeutic agents, both for the treatment of local diseases or for systemic therapies. With the arrival of newer innovations, a large number of breakthrough technologies have emerged for targeting a drug molecule to the colon. Researchers have attempted various approaches in the development of these formulation technologies, such as pH-dependent, time-dependent and microflora-activated systems. Recently, a number of approaches have been proposed that utilize a novel concept of di-dependent drugdeliverysystems, that is, the systems in which the drug release is controlled by two factors: pH and time, and pH and microflora of the colon. This Editorial article is not intended to offer a comprehensive review on drugdelivery, but shall familiarize the readers with the formulation technologies that have been developed for attaining colon-specific drugdelivery. PMID:21933030
Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Oral drugdelivery remains the preferred route for administration of various drugs. Recent developments in the technology have prompted scientists to develop FDTs with improved patient compliance and convenience. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. The popularity and usefulness of the formulation resulted in development of several FDT technologies. FDTs are solid unit dosage forms, which disintegrate or dissolve rapidly in the mouth without chewing and water. FDTs or orally disintegrating tablets provide an advantage particularly for pediatric and geriatric populations who have difficulty in swallowing conventional tablets and capsules. This review describes various formulations and technologies developed to achieve fast dissolution/dispersion of tablets in the oral cavity. In particular, this review describes in detail FDT technologies based on lyophilization, molding, sublimation, and compaction, as well as approaches to enhancing the FDT properties, such as spray drying and use of disintegrants. In addition, taste-masking technologies, experimental measurements of disintegration times, and dissolution are also discussed.
In search of an efficient transdermal drugdeliverysystem (TDDS), a polyhydroxyalkanoate (PHA)-based system with a polyamidoamine dendrimer was examined. Tamsulosin was used as the model drug. The dendrimer was found to act as the weak enhancer. By adding the dendrimer, the dendrimer-containing PHA matrix achieved the clinically required amount of tamsulosin permeating through the skin model. This is also
Bone formation and regeneration is a prolonged process that requires a slow drug release system to assist in the long-term recovery. A drug-deliverysystem is developed that allows for the controlled release of simvastin, without exhibiting the side effects associated with high concentrations of simvastatin, and is still capable of inducing constant bone formation. PMID:23184712
Chou, Joshua; Ito, Tomoko; Otsuka, Makoto; Ben-Nissan, Besim; Milthorpe, Bruce
The highly organized structure of the stratum corneum provides an effective barrier to the drugdelivery into or across the skin. To overcome this barrier function, penetration enhancers are always used in the transdermal and dermal drugdeliverysystems. However, the conventional chemical enhancers are often limited by their inability to delivery large and hydrophilic molecules, and few to date have been routinely incorporated into the transdermal formulations due to their incompatibility and local irritation issues. Therefore, there has been a search for the compounds that exhibit broad enhancing activity for more drugs without producing much irritation. More recently, the use of biomaterials has emerged as a novel method to increase the skin permeability. In this paper, we present an overview of the investigations on the feasibility and application of biomaterials as penetration enhancers for transdermal or dermal drugdeliverysystems. PMID:23763451
Drugdelivery to the ear is used to treat conditions of the middle and inner ear such as acute and chronic otitis media, Ménière's disease, sensorineural hearing loss and tinnitus. Drugs used include antibiotics, antifungals, steroids, local anesthetics and neuroprotective agents. A literature review was conducted searching Medline (1966-2012), Embase (1988-2012), the Cochrane Library and Ovid (1966-2012), using search terms 'drugdelivery', 'middle ear', 'inner ear' and 'transtympanic'. There are numerous methods of drugdelivery to the middle ear, which can be categorized as topical, systemic (intravenous), transtympanic and via the Eustachian tube. Localized treatments to the ear have the advantages of targeted drugdelivery allowing higher therapeutic doses and minimizing systemic side effects. The ideal scenario would be a carrier system that could cross the intact tympanic membrane loaded with drugs or biochemical agents for the treatment of middle and inner ear conditions. PMID:23323784
Hoskison, E; Daniel, M; Al-Zahid, S; Shakesheff, K M; Bayston, R; Birchall, J P
Hydrogels are the three-dimensional network structures obtained from a class of synthetic or natural polymers which can absorb and retain significant amount of water. These have attracted considerable attention in biochemical and biomedical fields since they have characteristics like swelling in aqueous medium, biocompatibility, pH and temperature sensitivity or sensitivity towards other stimuli which can be utilized for its controlled zero order release. The hydrogels reviewed in this paper are expected to explore and develop the new generation of self regulated deliverysystem having wide array of desirable achieved properties. PMID:23474030
Enhancement strategies are necessary to improve the dermal\\/transdermal bioavailability of drugs applied to the skin due to\\u000a its amazing barrier, the stratum corneum. Strategies to overcome this barrier, thus improving drug release to the skin include\\u000a the use of penetration enhancers, specific deliverysystems, supersaturated solutions and physical methods (iontophoresis,\\u000a electroporation and ultrasound). Delivery of active agents to the skin
Maria Bernadete Riemma Pierre; Irina dos Santos Miranda Costa
Proposes a new concept of a micro-robot drugdeliverysystem (DDS) in which drug-carriers of air-filled microcapsules are measured with echography and are controlled with resonant ultrasound. The authors have confirmed physical possibility of resonance design of drug-carriers depending on shell structure of microcapsule. Furthermore, as a measurement system for microrobot DDS, they have developed novel echographic imaging system. Path
A system-on-a-chip (SOC) with integrated drug reservoirs for drugdelivery is proposed. Electrolysis is used to generate microbubbles, which are employed as a force to open the reservoirs and release the drug. Wireless components, including an on\\/off keying receiver, microcontrol unit, regulator, clock divider, and power-on reset, are integrated for remote drug activation. The proposed microchip is fabricated by Taiwan
Pen-Li Huang; Po-Hung Kuo; Yu-Jie Huang; Hsin-Hung Liao; Yao-Joe Joseph Yang; Tao Wang; Yao-Hung Wang; Shey-Shi Lu
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 drugdelivery. 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 drugdelivery through the SC.
The central problem in cancer chemotherapy is the severe toxic side effects of anticancer drugs on healthy tissues. Invariably the side effects impose dose reduction, treatment delay, or discontinuance of therapy. To limit the adverse side effects of cancer chemotherapy on healthy organs, we proposed a drugdeliverysystem (DDS) with specific targeting ligands for cancer cells. The proposed DDS
S. S. Dharap; Y. Wang; P. Chandna; J. J. Khandare; B. Qiu; S. Gunaseelan; P. J. Sinko; S. Stein; A. Farmanfarmaian; T. Minko
Summary Liposomes are microscopic, closed lipid vesicles able to entrap hydrophilic as well as lipophilic compounds. They constitute a versatile drugdeliverysystem. When injected by the intravenous route, liposomes are taken up by macrophages in the liver and in the spleen. Investigation of several animal models of infections has shown that liposome-entrapped anti-infectious drugs are active against infections due
Arterial infusion chemotherapy has become one of the major treatments for malignant tumors. Since 1988, we have attempted repeated arterial infusion of anticancer drugs using an implantable drugdeliverysystem in 68 patients who had inoperable hepatocellular carcinoma (HCC). Most of our patients could not undergo transcatheter arterial embolization (TAE) because of extreme tumor extension and\\/or accompanying advanced liver cirrhosis.
A novel microsphere drugdeliverysystem of ivermectin (IVM) using hydrophobic protein zein was prepared by the phase separation method and characterized by a scanning electron microscope and laser light scattering particle size analyzer. Releases of model drug IVM from zein microspheres, tabletted microspheres and pepsin degradation of tabletted microspheres were also performed in vitro to investigate the mechanism of
Xinming Liu; Qingshen Sun; Huajie Wang; Lei Zhang; Jin-Ye Wang
Although the significance of burst release in controlled deliverysystems has not been entirely ignored, no successful theories have been put forth to fully describe the phenomenon. Despite the fact that the fast release of drug in a burst stage is utilized in certain drug administration strategies, the negative effects brought about by burst can be pharmacologically dangerous and economically
To improve the dissolution rate of ibuprofen, a model poorly water soluble drug, self-nanoemulsifying drugdeliverysystems (SNEDDS) were developed. Various surfactants and oils were screened as candidates for SNEDDS on the basis of droplet size of the resulting emulsions. The influence of the constituent structure, concentration and the composition of SNEDDS formulations, and the emulsifier HLB value, on the
Lijuan Wang; Jinfeng Dong; Jing Chen; Julian Eastoe; Xuefeng Li
Hypoxia is a characteristic feature of a number of diseases including some cancers, rheumatoid arthritis and diabetes. Hypoxic tissue facilitates the use of bioreductive drug targeting systems as oxygen suppresses the release of the active drug. This review focuses on bioreductive delivery where accompanying intramolecular cyclisation negates adduct formation between the bioreductive and macromolecules such as DNA. To date, three
Development and optimization of novel production techniques for drugdeliverysystems are fundamental steps in the “from the bench to the bedside” process which is the base of translational medicine. In particular, in the current scenery where the need for reducing energy consumption, emissions, wastes and risks drives the development of sustainable processes, new pharmaceutical manufacturing does not constitute an exception. In this paper, concepts of process intensification are presented and their transposition in drugdeliverysystems production is discussed. Moreover, some examples on intensified techniques, for drug microencapsulation and granules drying, are reported.
Barba, Anna Angela; Dalmoro, Annalisa; d'Amore, Matteo
Development and optimization of novel production techniques for drugdeliverysystems are fundamental steps in the "from the bench to the bedside" process which is the base of translational medicine. In particular, in the current scenery where the need for reducing energy consumption, emissions, wastes and risks drives the development of sustainable processes, new pharmaceutical manufacturing does not constitute an exception. In this paper, concepts of process intensification are presented and their transposition in drugdeliverysystems production is discussed. Moreover, some examples on intensified techniques, for drug microencapsulation and granules drying, are reported. PMID:23905058
Barba, Anna Angela; Dalmoro, Annalisa; d'Amore, Matteo
A novel folate-decorated and graphene mediated drugdeliverysystem was prepared that involves uniquely combining graphene oxide (GO) with anticancer drug for controlled drug release. The nanocarrier system was synthesized by attaching doxorubicin (DOX) to graphene oxide via strong ?–? stacking interaction, followed by encapsulation of graphene oxide with folic acid conjugated chitosan. The ?–? stacking interaction, simplified as a
Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drugdeliverysystems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drugdeliverysystems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drugdeliverysystems for cancer therapies.
Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drugdeliverysystems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drugdeliverysystems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drugdeliverysystems for cancer therapies.
A novel composite material consisting of a silica aerogel core coated by a poly(ethylene) glycol (PEG) hydrogel was developed. The potential of this novel composite as a drugdeliverysystem was tested with ketoprofen as a model drug due to its solubility in supercritical carbon dioxide. The results indicated that both drug loading capacity and drug release profiles could be tuned by changing hydrophobicity of aerogels, and that drug loading capacity increased with decreased hydrophobicity, while slower release rates were achieved with increased hydrophobicity. Furthermore, higher concentration of PEG diacrylate in the prepolymer solution of the hydrogel coating delayed the release of the drug which can be attributed to the lower permeability at higher PEG diacrylate concentrations. The novel composite developed in this study can be easily implemented to achieve the controlled delivery of various drugs and/or proteins for specific applications. PMID:22374682
Giray, Seda; Bal, Tu?ba; Kartal, Ayse M; K?z?lel, Seda; Erkey, Can
This study aims to formulate and evaluate bioavailability of a self-nanoemulsified drugdeliverysystem (SNEDDS) of a poorly\\u000a water-soluble herbal active component oleanolic acid (OA) for oral delivery. Solubility of OA under different systems was\\u000a determined for excipient selection purpose. Four formulations, where OA was fixed at the concentration of 20 mg\\/g, were prepared\\u000a utilizing Sefsol 218 as oil phase, Cremophor
Jia Xi; Qi Chang; Chak K. Chan; Zhao Yu Meng; Geng Nan Wang; Jia Bei Sun; Yi Tao Wang; Henry H. Y. Tong; Ying Zheng
Abstract A diverse range of drugdelivery vehicles have been developed to specifically target chemotherapeutics to solid tumours while avoiding systemic dose-limiting toxicity. Many of these active targeting strategies display limited efficacy because they rely on subtle differences in expression patterns between pathogenic tissue and healthy tissue. In contrast, drugdeliverysystems that exploit thermoresponsive behaviour allow a clinician to spatially and temporally control the accumulation and/or release of the toxic agents within tumour tissue by simply applying mild hyperthermia (defined as 39-43?°C) to the desired site. Although thermally sensitive materials comprise a significant portion of the literature on novel drugdeliverysystems, only a few systems have been methodically tuned to respond within this narrowly defined physiological temperature range in an in vivo environment. This review discusses the materials and strategies developed to control the primary tumour through the combined application of hyperthermia and chemotherapy. PMID:23924317
McDaniel, Jonathan R; Dewhirst, Mark W; Chilkoti, Ashutosh
This update review is on mucoadhesive polymers used in nasal dosage forms. The nasal mucosa provides a potentially good route for systemicdrugdelivery. One of the most important features of the nasal route is that it avoids first-pass hepatic metabolism, thereby reducing metabolism. The application of mucoadhesive polymers in nasal drugdeliverysystems has gained to promote dosage form residence time in the nasal cavity as well as improving intimacy of contact with absorptive membranes of the biological system. The various new technology uses in development of nasal drugdelivery dosage forms are discussed. The various dosage forms are vesicular carriers (liposome, noisome), nanostructured particles, prodrugs, in situ gelling system with special attention to in vivo studies.
Gamma radiation was used as the initiator/crosslinker agent for the synthesis of thermo-sensitive hydrogel networks, under the form of membranes, using dextran and N-isopropylacrylamide. The prepared membranes were loaded with Ondansetron™, a potent antiemetic drug and tested as drugdeliverysystems. The characterization of the materials was accomplished by: Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy, elemental analysis, lower critical solution temperature (LCST) determination, swelling behaviour evaluation, determination of surface energy by contact angle measurement and drugdelivery kinetics studies. Also, the influence of irradiation time and temperature on the materials properties was evaluated. PMID:23831900
Almeida, J F; Ferreira, P; Alves, P; Lopes, A; Gil, M H
We present a new approach within mathematical formalisms for the problem of self assembly in molecular systems automation and its application in targeted drugdelivery for cancer treatment. The problem under study concentrates its main focus on nano-robot control systems design including systems casualty, state notation and automata. We also describe the theory of nano-scale thermodynamically driven self assembly for
The aim of the study was to develop and evaluate a self--emulsifying drugdeliverysystem (SEDDS) formulation to improve solubility and dissolution and to enhance systemic exposure of a BCS class II anthelmetic drug, albendazole (ABZ). In the present study, solubility of ABZ was determined in various oils, surfactants and co-surfactants to identify the microemulsion components. Pseudoternary phase diagrams were plotted to identify the microemulsification existence area. SEDDS formulation of ABZ was prepared using oil (Labrafac Lipopfile WL1349) and a surfactant/co-surfactant (Tween 80/PEG 400) mixture and was characterized by appropriate studies, viz., microemulsifying properties, droplet size measurement, in vitro dissolution, etc. Finally, PK of the ABZ SEDDS formulation was performed on rats in parallel with suspension formulation. It was concluded that the SEDDS formulation approach can be used to improve the dissolution and systemic exposure of poorly water-soluble drugs such as ABZ. PMID:24000442
Noscapine, a tubulin binding anticancer agent undergoing Phase I/II clinical trials, inhibits tumor growth in nude mice bearing human xenografts of breast, lung, ovarian, brain, and prostrate origin. The analogues of noscapine like 9-bromonoscapine (EM011) are 5 to 10-fold more active than parent compound, noscapine. Noscapinoids inhibit the proliferation of cancer cells that are resistant to paclitaxel and epothilone. Noscapine also potentiated the anticancer activity of doxorubicin in a synergistic manner against triple negative breast cancer (TNBC). However, physicochemical and pharmacokinetic (ED50˜300-600 mg/kg bodyweight) limitations of noscapine present hurdle in development of commercial anticancer formulations. Therefore, objectives of the present review are to summarize the chemotherapeutic potential of noscapine and implications of nanoscale based drugdeliverysystems in enhancing the therapeutic efficacy of noscapine in cancer cells. We have constructed noscapine-enveloped gelatin nanoparticles, NPs and poly (ethylene glycol) grafted gelatin NPs as well as inclusion complex of noscapine in ?-cyclodextrin (?-CD) and evaluated their physicochemical characteristics. The Fe3O4 NPs were also used to incorporate noscapine in its polymeric nanomatrix system where molecular weight of the polymer governed the encapsulation efficiency of drug. The enhanced noscapine delivery using ?PAR-targeted optical-MR imaging trackable NPs offer a great potential for image directed targeted delivery of noscapine. Human Serum Albumin NPs (150-300 nm) as efficient noscapine drugdeliverysystems have also been developed for potential use in breast cancer. PMID:22571485
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 drugdelivery 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 drugdelivery in musculoskeletal disorder treatments can address some of the critical issues more effectively and efficiently than the systemicdelivery. 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.
For years, the field of drugdelivery has focused on (1) controlling the release of a therapeutic and (2) targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drugdelivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drugdelivery vehicles. This review describes the most recent advances in "smart" drugdeliverysystems that respond to one or multiple stimuli.
For years, the field of drugdelivery has focused on (1) controlling the release of a therapeutic and (2) targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drugdelivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drugdelivery vehicles. This review describes the most recent advances in "smart" drugdeliverysystems that respond to one or multiple stimuli. PMID:21114841
You, Jin-Oh; Almeda, Dariela; Ye, George Jc; Auguste, Debra T
Several methods are being employed to improve the oral bioavailability of lipophilic drugs like using inert lipid vehicles such as Oils, Surfactant dispersions, Self Microemulsifying DrugDeliverySystems (SMEDDS) and Liposomes. SMEDDS is formulated with the help of oil or suitable lipid materials, Surfactants and hydrophilic Co-surfactants. Mixture of above ingredients can be filled in a soft capsule and ingested. When the mixture comes in contact with gastrointestinal fluid it forms a stable O/W Microemulsion. A pseudo ternary phase diagram is used for identifying the efficient Self micro-emulsification region. SMEDDS can be formulated to give sustained release by use of inert polymers. When this polymer comes in contact with GI fluids, it forms gelled polymeric matrix, which releases the micro-emulsified active principle in a continuous and prolonged manner. Physical characterization of SMEDDS should be carried out by droplet size analysis and spontaneity of emulsification. The purpose of this review is to provide a brief out line of the formulation of SMEDDS, possible mode for improving bioavailability, fate and evaluation of the same. PMID:19534704
The therapeutic effectiveness of chemotherapy is optimal only when tumor cells are subjected to a maximum drug exposure. To increase the intratumoral drug concentration and thus the efficacy of chemotherapy, a thermoresponsive bubble-generating liposomal system is proposed for triggering localized extracellular drugdelivery. The key component of this liposomal formulation is the encapsulated ammonium bicarbonate (ABC), which is used to create the transmembrane gradient needed for a highly efficient encapsulation of doxorubicin (DOX). At an elevated temperature (42 °C), decomposition of ABC generates CO(2) bubbles, creating permeable defects in the lipid bilayer that rapidly release DOX and instantly increase the drug concentration locally. Because the generated CO(2) bubbles are hyperechogenic, they also enhance ultrasound imaging. Consequently, this new liposomal system encapsulated with ABC may also provide an ability to monitor a temperature-controlled drugdelivery process. PMID:23240550
For application in a portable transdermal drug-deliverysystem, novel transducers have been designed to enhance insulin transmission across skin using ultrasound. Previous research has shown transdermal delivery of insulin across skin using commercial sonicators operating at 20 kHz with intensities ranging from 12.5 to 225 mW\\/cm2. The goal of this research was to design and construct a small, lightweight transducer
Emiliano Maione; K. Kirk Shung; Richard J. Meyer; Jack W. Hughes; Robcrt E. Newnham; Nadine Barrie Smith
Cellulose esters have played a vital role in the development of modern drugdelivery technology. They possess properties that\\u000a are not only well-suited to the needs of pharmaceutical applications, but that enable construction of drugdeliverysystems\\u000a that address critical patient needs. These properties include very low toxicity, endogenous and\\/or dietary decomposition products,\\u000a stability, high water permeability, high T\\u000a g,
The main purpose of this study was to prepare lipid-based self-microemulsifying drugdeliverysystem (SMEDDS) to improve peroral bioavailability of silymarin. SMEDDS was a system consisting of silymarin, Tween 80, ethyl alcohol, and ethyl linoleate. Particle size change of the microemulsion was evaluated upon dilution with aqueous media and loading with incremental amount of silymarin. In vitro release was investigated
Purpose: The aim of this in vitro study was to compare different catheter systems for local drugdelivery with respect to the penetration depth of a biotin marker solution delivered into the vessel wall. Methods: Post-mortem carotid arteries from pigs were locally infused with a biotin solution using three different catheter systems. With all catheters (microporous balloon catheter, hydrogel-coated balloon
Heiko Alfke; Hans-Joachim Wagner; Christian Calmer; Klaus Jochen Klose
This paper describes a novel approach for designing drugdeliverysystems for intra-articular (i.a.) treatment of rheumatoid arthritis. Retention of these systems was evaluated by radiolabeling with Tc-99m and gamma scintigraphy in arthritic rabbits. Liposome, niosome, lipogelosome and niogelosome formulations of Diclofenac Sodium (DFNa) have been prepared and drug release properties and in vitro characterisation studies have been carried out. According to characterisation results L1 (DMPC: CHOL: DCP (7:1:2)), L1J1 (DMPC: CHOL: DCP (7:1:2) in C-940 1:1 (w/w)), N (SUR I: CHOL: DCP (7:1:2)) and NJ1 (SUR I: CHOL: DCP (7:1:2) in C-940 1:1 (w/w)) formulations were chosen for the further studies. Retention time of these formulations was evaluated by gamma scintigraphic imaging studies. Rabbits with antigen-induced arthritis were injected intra-articularly with Tc-99m labelled drugdeliverysystems. Serial scintigraphic images were obtained to investigate the retentions of labelled drugdeliverysystems in the arthritic joints and choose a suitable formulation for the treatment protocol of arthritis. At the end of the scintigraphic imaging studies it was observed that radiolabelled lipogelosome formulation containing DFNa (L1J1) retained much longer in the experimentally arthritic knee joints of the rabbits. This formulation was used for the treatment protocol of arthritis. Mono articular arthritis was induced in the knee joints of rabbits and it was monitored at regular time intervals by measuring changes in knee joint diameter. Also macroscopic and histopathologic evaluations were performed for further evaluation of arthritis. Great retention of DFNa in the arthritic joint might reduce potential adverse systemic effects of the drug because of local administration into the diseased area. It appeared to be a promising drugdeliverysystem for intra-articular drugdelivery. PMID:15885453
Novel drugdeliverysystems were developed for peroral administration of peptide and protein drugs for site specific mechanical fixation at the gut wall and with specific release patterns. These so-called shuttle systems were designed by using superporous hydrogels (SPH) and SPH composite (SPHC) as the conveyor of a core which contained the model compound N-?-benzoyl-l-arginine ethylester (BAEE). Two different types
Farid A Dorkoosh; J. C Verhoef; G Borchard; M Rafiee-Tehrani; Hans E Junginger
After oral administration, the majority of drug molecules are absorbed across the small intestine and enter the systemic circulation via the portal vein and the liver. For some highly lipophilic drugs (typically log P>5, lipid solubility>50 mg\\/g), however, association with lymph lipoproteins in the enterocyte leads to transport to the systemic circulation via the intestinal lymph. The attendant delivery benefits associated
Natalie L. Trevaskis; William N. Charman; Christopher J. H. Porter
The main objective of this study was to prepare a solid form of lipid-based self-emulsifying drugdeliverysystem (SEDDS) by spray drying liquid SEDDS with an inert solid carrier Aerosil 200 to improve the oral bioavailability of poorly water-soluble drug dexibuprofen. The liquid SEDDS was a system that consisted of dexibuprofen, Labrasol, Capryol 90 and Labrafil M 1944 CS. The
Prabagar Balakrishnan; Beom-Jin Lee; Dong Hoon Oh; Jong Oh Kim; Myung Ja Hong; Jun-Pil Jee; Jung Ae Kim; Bong Kyu Yoo; Jong Soo Woo; Chul Soon Yong; Han-Gon Choi
Particle Replication in Non-Wetting Templates (PRINT®) is a platform particle drugdelivery technology that coopts the precision and nanoscale spatial resolution inherently afforded by lithographic techniques derived from the microelectronics industry to produce precisely engineered particles. We describe the utility of PRINT technology as a strategy for formulation and delivery of small molecule and biologic therapeutics, highlighting previous studies where particle size, shape, and chemistry have been used to enhance systemic particle distribution properties. In addition, we introduce the application of PRINT technology towards respiratory drugdelivery, a particular interest due to the pharmaceutical need for increased control over dry powder characteristics to improve drugdelivery and therapeutic indices. To this end, we have produced dry powder particles with micro- and nanoscale geometric features and composed of small molecule and protein therapeutics. Aerosols generated from these particles show attractive properties for efficient pulmonary delivery and differential respiratory deposition characteristics based on particle geometry. This work highlights the advantages of adopting proven microfabrication techniques in achieving unprecedented control over particle geometric design for drugdelivery.
Garcia, Andres; Mack, Peter; Williams, Stuart; Fromen, Catherine; Shen, Tammy; Tully, Janet; Pillai, Jonathan; Kuehl, Philip; Napier, Mary; DeSimone, Joseph M.; Maynor, Benjamin W.
One of the big challenges of medicine today is to deliver drugs specifically to defected cells. Nanoparticulate drug carriers have the potential to answer to this call, as nanoparticles can cross physiological barriers and access different tissues, and also be provided in a targetable form aimed at enhancing cell specificity of the carrier. Recent developments within material science and strong collaborative efforts crossing disciplinary borders have highlighted the potential of mesoporous silica nanoparticles (MSNs) for such targeted drugdelivery. Here we outline recent advances which in this sense push MSNs to the forefront of drugdelivery development. Relatively straightforward inside-out tuning of the vehicles, high flexibility, and potential for sophisticated release mechanisms make these nanostructures promising candidates for targeted drugdelivery such as `smart' cancer therapies. Moreover, due to the large surface area and the controllable surface functionality of MSNs, they can be controllably loaded with large amounts of drugs and coupled to homing molecules to facilitate active targeting, simultaneously carrying traceable (fluorescent or magnetically active) modalities, also making them highly interesting as theragnostic agents. However, the increased relative surface area and small size, and flexible surface functionalization which is beneficially exploited in nanomedicine, consequently also includes potential risks in their interactions with biological systems. Therefore, we also discuss some safety issues regarding MSNs and highlight how different features of the drugdelivery platform influence their behaviour in a biological setting. Addressing these burning questions will facilitate the application of MSNs in nanomedicine.
Rosenholm, Jessica M.; Sahlgren, Cecilia; Lindén, Mika
Liposomal formulations of drugs have been shown to enhance drug efficacy by prolonging circulation time, increasing local concentration and reducing off-target effects. Controlled release from these formulations would increase their utility, and hyperthermia has been explored as a stimulus for targeted delivery of encapsulated drugs. Use of lasers as a thermal source could provide improved control over the release of the drug from the liposomes with minimal collateral tissue damage. Appropriate methods for assessing local release after systemicdelivery would aid in testing and development of better formulations. We use in vivo bioluminescence imaging to investigate the spatiotemporal distribution of luciferin, used as a model small molecule, and demonstrate laser-induced release from liposomes in animal models after systemicdelivery. These liposomes were tested for luciferin release between 37 and 45 °C in PBS and serum using bioluminescence measurements. In vivo studies were performed on transgenic reporter mice that express luciferase constitutively throughout the body, thus providing a noninvasive readout for controlled release following systemicdelivery. An Nd:YLF laser was used (527 nm) to heat tissues and induce rupture of the intravenously delivered liposomes in target tissues. These data demonstrate laser-mediated control of small molecule delivery using thermally sensitive liposomal formulations.
Mackanos, Mark A.; Larabi, Malika; Shinde, Rajesh; Simanovskii, Dmitrii M.; Guccione, Samira; Contag, Christopher H.
The present work aims at computational analysis of environmentally responsive hydrogels with enormous prospective in the formulation aspect of drugdeliverysystems. The drugdelivery potential of hydrogels to the targets is owing to the specific stimuli responsive nature of the hydrogels. The environmental factors looked upon in the study are changes in pH, alteration of temperature and glucose concentration rise originated in the body as a result of various disease conditions. Polymers, synthetic polypeptides and dendrimers have been used in the present work to study the feasibility of drugdelivery. The computational methods have been used to formulate polymer properties, pharmacokinetics and toxicity studies. Diverse interactions approximating electrostatic, hydrophobic and hydrogen bond interactions acquire place during incorporation of drugs within the polymer and dendrimers. The covalent and electrostatic interactions between a drug and the surface of polymer and dendrimer have been analyzed. The docking interaction studies have been performed and the best polymer and dendrimer complex have been selected based on the docking score, binding energy and interaction energy with the drugs. G5 generation of poly amidoamine dendrimers and poly N-Ndiethyl acrylamide (PDEAAM) have been identified as most suitable stimuli-responsive effective drug carriers for anti diabetic drugs and diuretics. Favorable results have been obtained while using poly acrylic acid (PAA) for corticosteroids and polylysine for diabetic drugs. ConA protein along with poly aspartic acid also showed good results. PMID:23106779
Namboori, P K Krishnan; Ranjini, U P; Manakadan, Asha A; Jose, Anila; Silvipriya, K S; Belzik, N; Deepak, O M
Ultrasound has been in use for the last three decades as amodality for diagnostic imaging in medicine. Recently, there have beennumerous reports on the application of nonthermal ultrasound energyfor targeting or controlling drug release. This new concept oftherapeutic ultrasound combined with drugs has led to much excitementin various medical fields. Ultrasound energy can enhance the effectsof thrombolytic agents such as
In the present study, novel environmentally responsive ophthalmic drugdeliverysystem composed of two gelling polymers with different phase transition mechanisms was developed in order to obtain sustained drug release in ocular cavity. Combination of polyacrylic acid (carbopol 934P) and xanthan gum was investigated as ophthalmic vehicle and assessed for its in vitro and in vivo performance. Different ratios of these polymers were used to prepare environmentally responsive ophthalmic drugdeliverysystem by simple mixing procedure. Developed formulation was assessed for physical tests such as appearance/clarity, pH, gelation; and performance characteristics such as drug content, rheological measurement, in vitro release, antimicrobial efficiency, in vivo studies for eye irritation, residence time estimation. Prepared formulation showed agreeable appearance/clarity, acceptable pH and good gelation property. In vitro and in vivo studies demonstrated adequate drug content, desired rheological behavior and reasonable in vitro and in vivo drug release property. In conclusion, the optimum concentration of polymers results in increased residence time and sustained drug release. On the basis of these findings, environmentally responsive system based on combination of carbopol and xanthan gum may be considered as a promising tool for ophthalmic delivery. PMID:22200332
A preliminary evaluation was carried out on metronidazole-loaded Self Emulsifying DrugDeliverySystem (SEDDS) using two vegetable oils-Palm Kernel Oil (PKO) and Palm Oil (PO). Purification of oils, drug solubility in the oils, pre\\/post formulation isotropicity tests, emulsification times and release studies of metronidazole from the SEDDS were carried out. Results indicated solubility values of 4.441 and 4.654%w\\/w, respectively for
Gentamicin sulfate has been incorporated in composites prepared from a SiO2–CaO–P2O5 bioactive glass and polymethylmethacrylate. Data showed that these materials could be used as drugdeliverysystem, keeping the bioactive behavior of the glass. The composites supply high doses of the antibiotic during the first hours when they are soaked in simulated body fluid (SBF). Thereafter, a slower drug release
Dexamethasone-loaded poly(ethylene-co-vinyl acetate) (EVAc) nanocomposites were fabricated via solution-casting with three different organosilicates for study in a drugdeliverysystem. X-ray diffraction (XRD) showed that all three nanocomposites were in an intercalated morphology. Release studies of dexamethasone into phosphate-buffered saline revealed that the presence of silicates reduced the rate of drug release, and this reduction was a function of volume
Stephen H. Cypes; W. Mark Saltzman; Emmanuel P. Giannelis
The purpose of this research was to prepare a gastroretentive drugdeliverysystem of ranitidine hydrochloride. Guar gum,\\u000a xanthan gum, and hydroxypropyl methylcellulose were evaluated for gel-forming properties. Sodium bicarbonate was incorporated\\u000a as a gas-generating agent. The effects of citric acid and stearic acid on drug release profile and floating properties were\\u000a investigated. The addition of stearic acid reduces the
Brijesh S. Dave; Avani F. Amin; Madhabhai M. Patel
The objective of this work was to develop a self-microemulsifying drugdeliverysystem (SMEDDS) for improving oral absorption\\u000a of poorly water-soluble drug, silymarin. The pseudo-ternary phase diagrams were constructed using ethyl linoleate, Cremophor\\u000a EL, ethyl alcohol, and normal saline to identify the efficient self-microemulsification region. The particle size and its\\u000a distribution of the resultant microemulsions were determined using dynamic light
Xinru Li; Quan Yuan; Yanqing Huang; Yanxia Zhou; Yan Liu
The use of non-functional and\\/or non-reactive pressure sensitive adhesives has recently been discovered to influence both drug release and adhesion properties in transdermal drugdeliverysystems (TDDSs). These advances have added simplicity in formulary composition, lack of safety concerns, and prolonged shelf-life of finished product. The versatility of these PSAs is provided by the ability of the adhesives to avoid
In this contribution, a novel smart drugdeliverysystem (DDS) consisting of hydroxyl-functionalized glycerol poly(?-caprolactone) (PGCL)-based microspheres and poly(N-isopropylacrylamide) (PNIPAAm) hydrogel was developed for prolonged and sustained controlled drug release. Various amounts PGCL-based microspheres were incorporated physically into temperature sensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel to form the novel DDSs. Resulting DDSs were characterized by scanning electron microscopy (SEM), differential scanning calorimetry
It was the purpose of this study to design and evaluate a new bioadhesive vaginal drugdeliverysystem for clotrimazole. Chitosan, a cationic biopolymer derived by deacetylation of chitin, was modified by the introduction of thioglycolic acid (TGA). The modification was achieved by utilising a carbodiimide to link the carboxylic acid moieties of TGA covalently to the primary amino groups
Constantia E. Kast; Claudia Valenta; Martina Leopold; Andreas Bernkop-Schnürch
Purpose: To evaluate the penetration of commercially available gatifloxacin and moxifloxacin into the anterior chamber of a rabbit eye using collagen shields presoaked in the antibiotics as a drugdeliverysystem. Methods: Collagen shields, presoaked for 10 min in commercially available solutions of gatifloxacin (diluted intravenous Tequin®) or moxifloxacin (VigamoxTM) with the same concentration, were placed on the surface of
Guy Kleinmann; Scott Larson; Brian Hunter; Scott Stevens; Nick Mamalis; Randall J. Olson
The characteristics of self-nanoemulsifying drugdeliverysystem (SNEDDS) of Anethole trithione (ATT) for oral administration by the combined use of surfactants were investigated. In combination with surfactants, the SNEDDS provided smaller particle size, more oil loading, and shorter emulsification time. ATT from the SNEDDS rapidly dissolved in dissolution media whereas the ATT tablets showed different dissolution patterns according to the
Ligusticum chuanxiong oil is a kind of volatile oil from rhizome of ligusticum Chuanxiong (VOC). It is pharmacologically active in treating a variety of diseases. However, the instability and poor water solubility have limited its further clinical application. In the present study, a self-microemulsifying drugdeliverysystem (SMEDDS) was developed and SMEDDS based formulation – VOC-SMEDDS capsules were prepared to
Ligusticum chuanxiong oil is a kind of volatile oil from rhizome of ligusticum Chuanxiong (VOC). It is pharmacologically active in treating a variety of diseases. However, the instability and poor water solubility have limited its further clinical application. In the present study, a self-microemulsifying drugdeliverysystem (SMEDDS) was developed and SMEDDS based formulation – VOC-SMEDDS capsules were prepared to
Enhancement strategies are necessary to improve the dermal/transdermal bioavailability of drugs applied to the skin due to its amazing barrier, the stratum corneum. Strategies to overcome this barrier, thus improving drug release to the skin include the use of penetration enhancers, specific deliverysystems, supersaturated solutions and physical methods (iontophoresis, electroporation and ultrasound). Delivery of active agents to the skin by liposomal carriers has improved topical therapy in the field of dermatology. The interest in these carriers is based on their potential to enclose various types of biological materials and to deliver them to diverse cell types. Particularly, in recent years liposomes have been shown to be a promising drug-deliverysystem to the skin. Their use may produce several-fold higher drug concentrations in the epidermis and dermis and lower systemic concentrations when compared to conventional dosage forms. On the other hand, special characteristic vesicles like ethosomes, transfersomes and niosomes may be potential transdermal deliverysystems for ionic molecules and polypeptides. PMID:21805180
Pierre, Maria Bernadete Riemma; Dos Santos Miranda Costa, Irina
This paper reports on the experimental characterization of a robotic drugdeliverysystem based on an endoscopic capsule propelled in water and silicone oil using electromagnetic actuation. Silicon oil is specifically chosen to mimic the viscous environment in the gastrointestinal (GI) tract within the human body. A permanent magnet is embedded inside the capsule to make it responsive to the
A new hydrogel, with scleroglucan using borax as a crosslinker, has been prepared. The physical gel has been loaded with a model molecule (theophylline) and the release of the drug from the gel was evaluated. The same system was used to prepare tablets and the delivery of theophylline in different environmental conditions (HCl and SIF) was determined. A recent theoretical
T. Coviello; M. Grassi; R. Lapasin; A. Marino; F. Alhaique
A computerized drugdeliverysystem has been designed and tested for automatic regulation of mean arterial blood pressure (MAP) of human patients by infusion of a vasodilator (sodium nitroprusside). Its control algorithm belongs to a type of long-range predictive control with a combination of finite-horizon and an infinite horizon optimization terms. The controller operates in an adaptive mode by using
K. Ezra Kwok; Sirish L. Shah; Barry A. Finegan; Gary K. Kwong
This report describes an ambulatory infusion device developed to provide parenteral drugdelivery at a precisely controlled rate. The device is based on the innovative and unique concept of utilizing electrohydrolysis of a negatively charged hydrogel. The system consists of two modules: a pump unit and an electronic control unit. The pump module, which can be a disposable unit, contains
Casein, the major milk protein, forms an integral part of the daily diet in many parts of the world. Casein possesses a number of interesting properties that make it a good candidate for conventional and novel drugdeliverysystems. This article reviews approaches aimed to associate bioactive molecules to casein and analyze the evidence of their efficacy in modifying the
Ahmed O. Elzoghby; Wael S. Abo El-Fotoh; Nazik A. Elgindy
The major problem in oral drug formulations is low and erratic bioavailability, which mainly results from poor aqueous solubility. This may lead to high inter- and intra subject variability, lack of dose proportionality and therapeutic failure. The improvement of bio-availability of drugs with such properties presents one of the greatest challenges in drug formulations. Oral lipid based formulations are attracting considerable attention due to their capacity to increase the solubility, facilitating gastrointestinal absorption and reduce or eliminate the effect of food on the absorption of poorly water soluble, lipophilic drug and thus increasing the bioavailability. The present review outlines the recent findings on self-emulsifying drugdeliverysystem (SEDDS), self-micro/nanoemulsifying drugdeliverysystem (SMEDDS/SNEDDS) and evaluation of these formulations published over the past decade. The application of lipid based formulations as a promising system for the oral delivery of many therapeutic agents including traditional medicine (TM) has also been examined in the current review. PMID:21453264
Composite microparticle drugdeliverysystems based on chitosan, alginate and pectin with improved pH sensitivity were developed for oral delivery of protein drugs, using bovine serum albumin (BSA) as a model drug. The composite drug-loaded microparticles with a mean particle size less than 200mum were prepared by a convenient shredding method. Since the microparticles were formed by tripolyphosphate cross-linking, electrostatic complexation by alginate and/or pectin, as well as ionotropic gelation with calcium ions, the microparticles exhibited an improved pH-sensitive drug release property. The in vitro drug release behaviors of the microparticles were studied in simulated gastric (pH 1.2 and pH 5.0), intestinal (pH 7.4) and colonic (pH 6.0 and pH 6.8 with enzyme) media. For the composite microparticles with suitable compositions, the releases of BSA at pH 1.2 and pH 5.0 could be effectively sustained, while the releases at pH 7.4, pH 6.8 and pH 6.0 increased significantly, especially in the presence of pectinase. These results clearly suggested that the microparticles had potential for site-specific protein drugdelivery through oral administration. PMID:19058952
The aim of the current study was the development of a new pellet based self-emulsifying (SE) drugdeliverysystem for the oral delivery of poorly soluble drugs. Furthermore, we wanted to investigate the influence of physiological dilution media and enzymatic digestion on the solubilization capacity of the formulation for the model drug Progesterone.Lipid mixtures composed of Solutol® HS 15 and
Long viewed as the 'method of choice' for characterizing thermodynamics and stoichiometry of molecular interactions, with high sensitivity, isothermal titration calorimetry (ITC) has been applied to many areas of pharmaceutical analysis. This review highlights ITC employment to measure binding thermodynamics and their use for pharmaceutical formulations and drugdeliverysystem characterization particularly cyclodextrin-guest interactions, investigation of micellar-based systems, polyelectrolytes, nucleic acid interactions with multivalent cations and the optimization of DNA targeting and delivery. Furthermore, the potential of ITC for the characterization of different functionalities carried by nanoparticles as well as their interaction with living systems was outlined. PMID:18617012
The cephalosporin class antibacterial agent, cefazolin, was intercalated into layered double hydroxides (LDHs) in order to improve the drug efficiency as well as to achieve the controlled release property. Cefazolin molecules were incorporated into LDH through conventional ion exchange reaction. X-ray diffraction pattern analyses confirmed that cefazolin molecules were intercalated between the interlayer spaces of LDH. Fourier-transform infrared spectra and
Seung-Jin Ryu; Hyun Jung; Jae-Min Oh; Jin-Kyu Lee; Jin-Ho Choy
We report on a new method for enhancing the specificity of drugdelivery for tumor cells, using thermosensitive immunoliposomes. The liposomes are conjugated to the antibody trastuzumab (Herceptin), which targets the human epidermal growth factor receptor 2 (Her-2), a cell membrane receptor overexpressed in many human cancers. Being thermosensitive, the liposomes only release their contents when heated slightly above body temperature, allowing for the possibility of tissue targeting through localized hyperthermia. Using self-quenching calcein, we demonstrate the release of liposome contents into cell endosomes after brief heating to 42 degrees C. To further increase targeting specificity, we incorporate the concept of a two-component deliverysystem that requires the interaction of two different liposomes within the same endosome for cytoplasmic delivery. Experimental evaluation of the technique using fluorescently labeled liposomes shows that a two-component deliverysystem, combined with intracellular disruption of liposomes by hyperthermia, significantly increases specificity for Her-2-overexpressing tumor cells. PMID:19089689
The development and optimization of many new drug therapies requires long-term local delivery with controlled, but variable dosage. Current methods for chronic drugdelivery have limited utility because they either cannot deliver drugs locally to a specific organ or tissue, do not permit changes in delivery rate in situ, or cannot be used in clinical trials in an untethered, wearable configuration. Here, we describe a small, self-contained system for liquid-phase drugdelivery. This system enables studies lasting several months and infusion rates can be programmed and modified remotely. A commercial miniature pump is integrated with microfabricated components to generate ultralow flow rates and stroke volumes. Solutions are delivered in pulses as small as 370 nL, with pulses delivered at any interval of 1 min or longer. A unique feature of the system is the ability to infuse and immediately withdraw liquid, resulting in zero net volume transfer while compounds are exchanged by mixing and diffusion with endogenous fluid. We present in vitro results demonstrating repeatability of the delivered pulse volume for nearly 3 months. Furthermore, we present in vivo results in an otology application, infusing into the cochlea of a guinea pig a glutamate receptor antagonist, which causes localized and reversible changes in auditory sensitivity. PMID:19089621
Fiering, J; Mescher, M J; Leary Swan, E E; Holmboe, M E; Murphy, B A; Chen, Z; Peppi, M; Sewell, W F; McKenna, M J; Kujawa, S G; Borenstein, J T
Niosomes have potential applications in topical drugdeliverysystem. The objective of the study was to formulate and evaluate the niosome of Itraconazole. Surfactant?:?cholesterol ratio and quantity of ethanol used were studied by applying factorial design. Formulated niosomes were evaluated for vesicle size, entrapment efficiency, drug release, skin permeation, and antimycotic activity. Vesicle size, entrapment efficiency, and drug release were markedly dependent on surfactant?:?cholesterol ratio and quantity of ethanol used. Permeation of the drug through the skin was affected by cholesterol content in formulation. Itraconazole niosome were having larger zone of inhibition than marketed formulation when activity was checked against C. albicans. Niosomes may be a promising carrier for topical delivery of Itraconazole especially due to their simple production.
Due to its extreme lipophilicity, the oral delivery of cinnarizine (CN) encounters several problems such as poor aqueous solubility and pH-dependent dissolution, which result in low and erratic bioavailability. The current study aims to design self-nanoemulsifying drugdeliverysystems (SNEDDS) of CN that circumvent such obstacles. Equilibrium solubility of CN was determined in a range of anhydrous and diluted lipid-based formulations. Dynamic dispersion tests were carried out to investigate the efficiency of drug release and magnitude of precipitation that could occur upon aqueous dilution. Droplet sizes of selected formulations, upon (1:1,000) aqueous dilution, were presented. The optimal formulations were enrolled in subsequent dissolution studies. The results showed that increasing lipid chain length and surfactant lipophilicity raised the formulation solvent capacity, while adding co-solvents provoked a negative influence. The inclusion of mixed glycerides and/or hydrophilic surfactants improved the drug release efficiency. Generally, no significant precipitation was observed upon aqueous dilution of the formulations. Five formulations were optimal in terms of their superior self-emulsifying efficiency, drug solubility, dispersion characteristics, and lower droplet size. Furthermore, the optimal formulations showed superior dissolution profile compared to the marketed (Stugeron®) tablet. Most importantly, they could resist the intensive precipitation observed with the marketed tablet upon shifting from acidic to alkaline media. However, SNEDDS containing medium-chain mixed glycerides showed the highest drug release rate and provide great potential to enhance the oral CN delivery. Accordingly, the lipid portion seems to be the most vital component in designing CN self-nanoemulsifying systems. PMID:22760454
Shahba, Ahmad Abdul-Wahhab; Mohsin, Kazi; Alanazi, Fars Kaed
Drugdeliverysystems for cancer therapeutics have now been used by millions of patients and have resulted in the creation of new therapies as well as significantly improving existing ones. Here we discuss a number of the drugdeliverysystems that have been approved by regulatory authorities and that are currently in clinical use, such as controlled delivery of cancer
Deep magnetic capture and clinical application are the current trends for magnetic targeted drugdeliverysystem. More promising and possible strategies are needed to overcome the current limitations and further improve the magnetic targeting technique. Recent advances in the development of targeting magnet system show promise in progressing this technology from the laboratory to the clinic. Starting from well-known basic concepts, current limitations of magnetic targeted drugdeliverysystem are analyzed. Meanwhile, the design concepts and evaluations of some effective improvements in magnet system are discussed and reviewed with reference to (i) reasonable design of magnet system; (ii) control modes of magnet system used to generate dynamical magnetic fields; and (iii) magnetic field driving types.
Tamoxifen citrate is an antiestrogen for peroral breast cancer treatment. The drugdelivery encounters problems of poor water solubility and vulnerability to enzymatic degradation in both intestine and liver. In the current study, tamoxifen citrate self-nanoemulsifying drugdeliverysystems (SNEDDS) were prepared in an attempt to circumvent such obstacles. Preliminary screening was carried out to select proper ingredient combinations. All surfactants screened were recognized for their bioactive aspects. Ternary phase diagrams were then constructed and an optimum system was designated. Three tamoxifen SNEDDS were then compared for optimization. The systems were assessed for robustness to dilution, globule size, cloud point, surface morphology and drug release. An optimum system composed of tamoxifen citrate (1.6%), Maisine 35-1 (16.4%), Caproyl 90 (32.8%), Cremophor RH40 (32.8%) and propylene glycol (16.4%) was selected. The system was robust to different dilution volumes and types. It possessed a mean globule size of 150 nm and a cloud point of 80 degrees C. Transmission electron microscopy demonstrated spherical particle morphology. The drug release from the selected formulation was significantly higher than other SNEDDS and drug suspension, as well. Realizing drug incorporation into an optimized nano-sized SNEDD system that encompasses a bioactive surfactant, our results proposed that the prepared system could be promising to improve oral efficacy of the tamoxifen citrate. PMID:19635537
Elnaggar, Yosra S R; El-Massik, Magda A; Abdallah, Ossama Y
Hydrogel nanoparticles have gained considerable attention in recent years as one of the most promising nanoparticulate drugdeliverysystems owing to their unique potentials via combining the characteristics of a hydrogel system (e.g., hydrophilicity and extremely high water content) with a nanoparticle (e.g., very small size). Several polymeric hydrogel nanoparticulate systems have been prepared and characterized in recent years, based
Polysaccharides-based nanoparticles were prepared by synthesized quaternized chitosan and dextran sulfate through simple ionic-gelation\\u000a self-assembled method. Introduction of quaternized groups was intended to increase water solubility of chitosan and make the\\u000a nanoparticles have broader pH sensitive range which can remain more stable in physiological pH and decrease the loss of protein\\u000a drugs caused by the gastric cavity. The load of
Shujun ShuLei; Lei Sun; Xinge Zhang; Zhongming Wu; Zhen Wang; Chaoxing Li
Modifying surfaces of nanoparticles (NPs) with polyethylene glycol (PEG), the so-called PEGylation, is the most commonly used method for reducing premature clearance of NPs from the circulation. However, several reports point out that PEGylation may negatively influence the performance of NPs as a drug carrier. Alternative surface modification strategies, including substitute polymers, conditional removal of PEG, and biomimetic surface modification, may provide solutions for the limitations of PEG. PMID:22231928
Modifying surfaces of nanoparticles (NPs) with polyethylene glycol (PEG), the so called PEGylation, is the most commonly used method for reducing premature clearance of NPs from the circulation. However, several reports point out that PEGylation may negatively influence the performance of NPs as a drug carrier. Alternative surface modification strategies, including substitute polymers, conditional removal of PEG, and biomimetic surface modification, may provide solutions for the limitations of PEG.
Poor penetration of anticancer drugs into solid tumors significantly limits their efficacy. This phenomenon has long been observed for small-molecule chemotherapeutics, and it can be even more pronounced for nanoscale therapies. Nanoparticles have enormous potential for the treatment of cancer due to their wide applicability as drugdelivery and imaging vehicles and their size-dependent accumulation into solid tumors by the enhanced permeability and retention (EPR) effect. Further, synthetic nanoparticles can be engineered to overcome barriers to drugdelivery. Despite their promise for the treatment of cancer, relatively little work has been done to study and improve their ability to diffuse into solid tumors following passive accumulation in the tumor vasculature. In this review, we present the complex issues governing efficient penetration of nanoscale therapies into solid tumors. The current methods available to researchers to study nanoparticle penetration into malignant tumors are described, and the most recent works studying the penetration of nanoscale materials into solid tumors are summarized. We conclude with an overview of the important nanoparticle design parameters governing their tumor penetration, as well as by highlighting critical directions in this field.
Multiscale computational modeling of drugdeliverysystems (DDS) is poised to provide predictive capabilities for the rational design of targeted drugdeliverysystems, including multi-functional nanoparticles. Realistic, mechanistic models can provide a framework for understanding the fundamental physico-chemical interactions between drug, deliverysystem, and patient. Multiscale computational modeling, however, is in its infancy even for conventional drugdelivery. The wide range of emerging nanotechnology systems for targeted delivery further increases the need for reliable in silico predictions. This review will present existing computational approaches at different scales in the design of traditional oral drugdeliverysystems. Subsequently, a multiscale framework for integrating continuum, stochastic, and computational chemistry models will be proposed and a case study will be presented for conventional DDS. The extension of this framework to emerging nanotechnology deliverysystems will be discussed along with future directions. While oral delivery is the focus of the review, the outlined computational approaches can be applied to other drugdeliverysystems as well.
Although bacterial nanocellulose (BNC) has reached enormous interest for biomedical applications because of its outstanding material properties, investigations about its potential as drugdeliverysystem are very rare. In the present study, for the first time, the applicability of BNC as drugdeliverysystem for proteins using serum albumin as model drug was systematically investigated. Additionally, never-dried BNC was compared with freeze-dried BNC. For both types of BNC, a dependency of concentration, temperature, time, and preswelling for albumin loading and release could be demonstrated. These findings indicated an overlay of diffusion- and swelling-controlled processes, which could be confirmed by Ritger-Peppas equation. Freeze-dried samples showed a lower uptake capacity for albumin than native BNC, which was found to be related to changes of the fiber network during the freeze drying process as demonstrated by electron microscopy and protein staining experiments. The integrity and biological activity of proteins could be retained during the loading and release processes, which was demonstrated by gel electrophoresis and the use of luciferase as biologically active molecule. In conclusion, hydrophilicity, high biocompatibility, and controllable drug loading and release render BNC an innovative and attractive biopolymer for controlled drugdelivery. PMID:23192666
Since the late 1960s, the field of drugdelivery has focused on the creation of new formulations with improved properties, taking much attention to drug release from the carrier. Liposomes and dendrimers represent two of the most studied drug carriers. A Modulatory Liposomal Controlled Release System (MLCRS) combining liposomal and dendrimeric technology has been recently published as well as Liposomal locked-in Dendrimers (LLDs) technology which was considered to be a class of MLCRSs. Chimeric advanced DrugDelivery nano Systems (chi-aDDnSs) can be defined as mixed nanosystems due to the combination of the bionanomaterials used and can offer advantages as drug carriers. This work deals with the production of two new chi-aDDnSs incorporating the newly synthesized dendrimer PG1. One of the two formulations bears the exact lipidic composition as the commercial liposomal drug "Myocet". Doxorubicin (Dox) was incorporated into conventional (free of dendrimer) liposomal formulations and into the corresponding chi-aDDnSs, and the physicochemical characteristics, the in vitro drug release and the in vitro cytotoxicity against human cancer cell lines were assessed. The results revealed a different modulation release effect of doxorubicin from the chi-aDDnS, compared to the Myocet replica. Pharmacological cytotoxicity concerning all the chi-aDDnSs was very close to that of the conventional liposomal systems. PMID:20934501
Magnetic nanocomposites (MNCs) have highly been acknowledged in the diagnostics and therapeutic applications. Particularly, the multifunctional MNCs have brought a variety of possibilities in targeted drugdelivery as well as non-invasive multimodality imaging. A temperature-responsive magnetic drugdeliverysystem has been developed which is made up of superparamagnetic iron oxide nanoparticles (SIONPs) core and Pluronic shell. The magnetic cores composed of congo red conjugated to SIONPs have been proved beneficial as multimodal imaging agents, while superparamagnetic properties facile conducting the nano or micro systems to the vicinity of targeted tissue. Polymer shell formed by stimuli-responsive Pluronic F127 poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) PEO-PPO-PEO block copolymer serves as the carrier for both hydrophilic and hydrophobic drugs. X-ray diffraction (XRD) and high-resolution transmission electron microscope (HR-TEM) were used to characterize as-synthesized MNCs. Furthermore, vibrating magnetometer experiments showed MNCs having a higher magnetization value than bare magnetic nanoparticles (MNPs) and easy to conduct with an external magnetic field. The hydrodynamic size of MNCs was found to be varying in response to the stimuli temperature. Once the temperature increased, the hydrodynamic radius of MNCs decreased. In addition, the feasibility of the system as a targeted drugdeliverysystem for Alzheimer's diseases (AD) diagnosis and therapy was studied. Searching for reliable targeting molecule, recent approaches for identification of amyloid-? (A?) and its derivatives have been evaluated. Consequently, the amyloid-derived diffusible ligands antibodies (anti-ADDLs) have been nominated as potential targeting molecules which can be attached to the MNCs system. The possibility of anti-ADDLs conjugation to DDS has been found promising for the multifunctional drugdeliverysystem for AD diagnosis and therapy. However, further experimental studies are required to assess the performance of the proposed DDS. PMID:23237189
Detonation nanodiamonds (NDs) are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drugdeliverysystems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drugdelivery and imaging biomaterials for use in animals and humans. PMID:23326195
Detonation nanodiamonds (NDs) are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drugdeliverysystems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drugdelivery and imaging biomaterials for use in animals and humans.
Solid dispersions can be used to improve dissolution of poorly soluble drugs and PVP is a common polymeric carrier in such systems. The mechanisms controlling release of drug from solid dispersions are not fully understood and proposed theories are dependent on an understanding of the dissolution behaviour of both components of the dispersion. This study uses microviscometry to measure small changes in the viscosity of the dissolution medium as the polymer dissolves from ibuprofen-PVP solid dispersions. The microviscometer determines the dynamic and kinematic viscosity of liquids based on the rolling/falling ball principle. Using a standard USP dissolution apparatus, the dissolution of the polymer from the solid dispersion was easily measured alongside drug release. Drug release was found to closely follow polymer dissolution at the molecular weights and ratios used. The combination of sensitivity and ease of use make microviscometry a valuable technique for the elucidation of mechanisms governing drug release from polymeric deliverysystems. PMID:15725569
Esnaashari, Solmaz; Javadzadeh, Yousef; Batchelor, Hannah K; Conway, Barbara R
Encapsulation of therapeutic and diagnostic materials into polymeric particles is a means to protect and control or target the release of active substances such as drugs, vaccines, and genetic material. In terms of mucosal delivery, polymeric encapsulation can be used to promote absorption of the active substance, while particles can improve the half-life of drugs administered systemically. Spray drying is an attractive technology used to produce such microparticles, because it combines both the encapsulation and drying steps in a rapid, single-step operation. Even so, spray drying is not classically associated with processes used for drug and therapeutic material encapsulation, since elevated temperatures could potentially denature the active substance. However, a comprehensive review of the literature revealed a number of studies demonstrating that spray drying can be used to produce microparticulate formulations with labile therapeutics. Polymers commonly employed include synthetics such as methacrylic copolymers and polyesters, and natural materials including chitosan and alginate. Drugs and active substances are diverse and included antibiotics, anti-inflammatory agents, and chemotherapeutics. Regarding the delivery of spray-dried particles, the pulmonary, oral, colonic, and nasal mucosal routes are often investigated because they offer a convenient means of administration, which promotes physician and patient compliance. In addition, spray drying has been widely used to produce polymeric microparticles for systemicdelivery in order to control the delivery of drugs, vaccines, or genetic material that may exhibit poor pharmacokinetic profiles or pose toxicity concerns. This review presents a brief introduction to the technology of spray drying and outlines the delivery routes and the applications of spray-dried polymeric microparticles. PMID:21043544
This paper reports a magnetic microvalve based on iron-powder filled polydimethysiloxane (PDMS) for implantable drugdeliverysystems, which allows transcutaneous control when implanted under the skin. It does not require any implanted power source or receiver including batteries, RF coils, piezoelectric materials, etc. Only a magnet is required to open the microvalve for drugdelivery. A pressurized balloon reservoir is
This report presents a transdermal drugdeliverysystem based on LIGA fabricated microparts. It is a portable device combining a magnetically actuated micro gear pump with a microneedle array. The fluidic behaviour of the system is analyzed in order to predict its performance according to the dimension of the microparts and then compared to experimental data. The manufacturing process of both micropump and microneedle array are described.
Matteucci, Marco; Perennes, Frederic; Marmiroli, Benedetta; di Fabrizio, Enzo
Targeted delivery of anticancer drugs is one of the most actively pursued goals in anticancer chemotherapy. A major disadvantage of anticancer drugs is their lack of selectivity for tumour tissue, which causes severe side effects and results in low cure rates. Any strategy by which a cytotoxic drug is targeted to the tumour, thus increasing the therapeutic index of the drug, is a way of improving cancer chemotherapy and minimizing systematic toxicity. This study covers the preparation of the gelatin microsphere (GM)-anti-bovine serum albumin (anti-BSA) conjugate for the development of a drug targeting approach for anticancer drugdelivery. Microspheres of 5% (w/v) gelatin content were prepared by crosslinking with glutaraldehyde (GTA) at 0.05 and 0.50% (v/v) concentration. Microspheres were in the size range of 71-141?microm. The suitability of these microspheres as drug carriers for anticancer drugdelivery was investigated in vitro by studying the release profiles of loaded methotrexate (MTX) and 5-fluorouracil (5-FU) and the cytotoxicities on cancer cell lines. The in vitro MTX release profiles (approximately 22-46% released in 24 h depending on the amount of GTA used) were much slower compared to 5-FU (approximately 42-91% released in 24 h). Both drugs demonstrated an initial fast release, which was followed by gradual, sustained drug release. The MTT cytotoxicity test results of GMs loaded with 5-FU and MTX showed approximately 54-70% and approximately 52-67% cytotoxicities in 4 days. In general, incorporation of MTX and 5-FU in microspheres enhanced the cytotoxic effect in a more prolonged manner compared to the free drugs. Gelatin micospheres were chemically conjugated to anti-BSA and the antigen-antibody activities were studied by immunofluorescence. Results indicated approximately 80% binding with conjugated anti-BSA and BSA-FITC. Based on their low cytotoxicity and the high antigen binding efficiencies, anti-BSA conjugated gelatin microspheres could be suitable targeted drug carrier systems for selective and long-term delivery of anticancer drugs to a specific body compartment (i.e. bladder cancer). PMID:16036303
The objective of the present study was to correlate the results of the in vitro release of a previously reported pulsatile drugdeliverysystem with the in vivo radio imaging study. The formulated drugdeliverysystem containing pellets of barium sulphate was administered to rabbits after overnight fast. Formulated dosage form, previously evaluated for in vitro drug release study, showed drug release after 6-10?h of lag time depending on the hardness as well as the thickness of the plug. Radio imaging study also showed that the plug in the capsule drugdeliverysystem remains intact for the period of 6?h. Thus, the formulated drugdeliverysystem is capable of delaying release in vitro as well as in rabbits for 6 hours. PMID:19905989
The focus on nanotechnology in cancer treatment and diagnosis has intensified due to the serious side effects caused by anticancer agents as a result of their cytotoxic actions on normal cells. This nonspecific action of chemotherapy has awakened a need for formulations capable of definitive targeting with enhanced tumor-killing. Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important area of nanomedicine. Currently several nanomaterial-based drug-deliverysystems are in vogue and several others are in various stages of development. Tumor-targeted drug-deliverysystems are envisioned as magic bullets for cancer therapy and several groups are working globally for development of robust systems.
Smart gel periodontal drugdeliverysystems (SGPDDS) containing gellan gum (0.1-0.8% w/v), lutrol F127 (14, 16, and 18% w/v), and ornidazole (1% w/v) were designed for the treatment of periodontal diseases. Each formulation was characterized in terms of in vitro gelling capacity, viscosity, rheology, content uniformity, in vitro drug release, and syringeability. In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.8% w/v of gellan gum and 16% w/v of lutrol F127 exhibited superior physical characteristics. PMID:20553104
While many drugdeliverysystems target constant, or zero-order drug release, certain drugs and hormones must be delivered in rhythmic pulses in order to achieve their optimal effect. Here we describe studies with two model autonomous rhythmic deliverysystems. The first system is driven by a pH oscillator that modulates the ionization state of a model drug, benzoic acid, which can permeate through a lipophilic membrane when the drug is uncharged. The second system is based on a nonlinear negative feedback instability that arises from coupling of swelling of a hydrogel membrane to an enzymatic reaction, with the hydrogel controlling access of substrate to the enzyme, and the enzyme's product controlling the hydrogel's swelling state. The latter system, whose autonomous oscillations are driven by glucose at constant external activity, is shown to deliver gonadotropin releasing hormone (GnRH) in rhythmic pulses, with periodicity of the same order as observed in sexually mature adult humans. Relevant experimental results and some mathematical models are reviewed.
Increasing acceptance of protein- and peptide-based drugs necessitates an investigation into the suitability of various sites for their administration. Colon is being investigated for delivery of such molecules. Colon-specific drugdelivery is designed to target drug molecules specifically to this area. Development of site-specific deliverysystems may exploit a specific property of the target site for drug activation\\/release. The gastrointestinal
Self-emulsifying drugdeliverysystems are a vital tool in solving low bioavailability issues of poorly soluble drugs. Hydrophobic drugs can be dissolved in these systems, enabling them to be administered as a unit dosage form for per-oral administration. When such a system is released in the lumen of the gastrointestinal tract, it disperses to form a fine emulsion (micro/nano) with the aid of GI fluid. This leads to in situ solubilization of drug that can subsequently be absorbed by lymphatic pathways, bypassing the hepatic first-pass effect. This article presents an exhaustive account of various literature reports on diverse types of self-emulsifying formulations with emphasis on their formulation, characterization and in vitro analysis, with examples of currently marketed preparations. PMID:20727418
In situ forming implants (ISFI) have shown promise in delivering adjuvant chemotherapy following minimally invasive cancer therapies such as thermal ablation of tumors. While ISFI systems have been thoroughly investigated for delivery of high molecular weight (Mw) therapeutics, little research has been conducted to optimize their design for delivery of low Mw drugs. This study examined the effect of varying the formulation components on the low Mw drug release profile from a ISFI consisting of poly(D,L-lactide-co-glycolide), fluorescein (model drug), and excipient dissolved in 1-methyl-2-pyrrolidinone (NMP). Effects of varying PLGA Mw, excipient concentration, and drug loading were studied. Additionally, solubility studies were conducted to determine the critical water concentration required for phase inversion. Results demonstrated that PLGA Mw was the most significant factor in modulating low Mw drug release from the ISFI systems. ISFI formulations comprised of a low Mw (16 kDa) PLGA showed a significantly (p<0.05) lower burst release (after 24 hours), 28.2 ± 0.5%, compared to higher Mw PLGA (60 kDa), 55.1 ± 3.1%. Critical water concentration studies also demonstrated that formulations with lower Mw PLGA had increased solubility in water and may thus require more time to phase invert and release the drug.
In particular since the last two decades there is constantly increasing interest in nanocarrier systems. They are utilized in order to overcome the major challenges being associated with this route of administration - namely poor solubility (I), poor permeability (II) and poor GI-stability (III). In order to improve drug solubility nanonization of the API, the use of solid lipid nanoparticles and porous adsorbent particles have shown great potential. Nanocrystals and selfnanoemulsifying drugdeliverysystems (SNEDDS) resulted already in numerous marketed drug products. Moreover, proof-of-principle studies for nanocarrier systems providing enhanced oral drug uptake are available. By providing a comparatively more intimate contact with the absorption membrane, a prolonged GI-residence time and/or exhibiting permeation enhancing properties, oral absorption can be strongly improved. Likely because of safety considerations and because of insufficiently high bioavailability improvements (<5-fold), however, a commercial interest in these systems is limited. Poor GI-stability can be overcome by incorporating the drug in nanocarrier systems providing a protective effect towards an enzymatic attack in the GI-tract. Furthermore, as nanocarrier systems can at least to some extent diffuse into the mucus gel layer releasing their payload there, a presystemic metabolism of the drug on the way between the deliverysystem and the absorption membrane can be excluded. Future trends are mainly focusing on carrier systems capable of not just improving solubility but providing also controlled drug release as well as on nanocarrier systems capable of efficiently permeating the mucus gel layer without destroying it. PMID:23537503
Importance of the field The advancement in material design and engineering has led to the rapid development of novel materials with increasing complexity and functions. Both non-degradable and degradable polymers have found wide applications in the controlled delivery field. Studies on drug release kinetics provide important information into the function of material systems. To elucidate the detailed transport mechanism and the structure-function relationship of a material system, it is critical to bridge the gap between the macroscopic data and the transport behavior at the molecular level. Areas covered in this review The structure and function information of selected non-degradable and degradable polymers have been collected and summarized from literatures published after 1990s. The release kinetics of selected drug compounds from various material systems will be discussed in case studies. Recent progresses in the mathematical models based on different transport mechanisms will be highlighted. What the reader will gain This article aims to provide an overview of structure-function relationships of selected non-degradable and degradable polymers as drugdelivery matrices. Take home message Understanding the structure-function relationship of the material system is key to the successful design of a deliverysystem for a particular application. Moreover, developing complex polymeric matrices requires more robust mathematical models to elucidate the solute transport mechanisms.
Objective of present study involves preparation and evaluation of self emulsifying drugdeliverysystem (SEDDS) of ibuprofen using peanut oil. SEDDS were composed of varying concentrations of peanut oil (solvent), tween 80 (surfactant) and span 20 (co-surfactant). Influence of concentration of surfactant/co-surfactant and globule size on dissolution rate was investigated. Dissolution rate was studied in phosphate buffer pH 6.8 using dissolution apparatus II. The dissolution rate of self emulsifying capsule was found to be significantly faster than that from conventional tablet. The optimized SEDDS released approximately above 85% of ibuprofen within 30 min, while conventional ibuprofen tablet could released only 36% in 30 min. Therefore, these SEDDS could be a better alternative to conventional drugdeliverysystem of ibuprofen. PMID:22876615
Macromolecular drugs hold great promise as novel therapeutics of several major disorders, such as cancer and cardiovascular disease. However, their use is limited by lack of efficient, safe, and specific delivery strategies. Successful development of such strategies requires interdisciplinary collaborations involving researchers with expertise on, e.g., polymer chemistry, cell biology, nanotechnology, systems biology, advanced imaging methods, and clinical medicine. This not only poses obvious challenges to the scientific community but also provides opportunities for the unexpected at the interface between different disciplines. This introductory chapter summarizes and gives references to studies on macromolecular delivery that should be of interest to a broad scientific audience involved in macromolecular drug synthesis as well as in vitro and in vivo drugdelivery studies. PMID:19085127
The aim of the present study was to develop a self-nanoemulsifying drugdeliverysystem (SNEDDS) for the oral delivery of Zedoary turmeric oil (ZTO), an essential oil extracted from the dry rhizome of Curcuma zedoaria. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification regions. ZTO could serve as a partial oil phase with the aid of the second oil phase to enhance drug loading. Increasing the surfactant concentration reduced the droplet size but increased the emulsification time, while the reverse effect was observed by increasing the co-surfactant concentration. Based on the emulsification time, droplet size and zeta potential after dispersion into aqueous phase, an optimized formulation consisting of ZTO, ethyl oleate, Tween 80, transcutol P (30.8:7.7:40.5:21, w/w) and loaded with 30% drug was prepared. Upon mixing with water, the formulation was rapidly dispersed into fine droplets with a mean size of 68.3+/-1.6 nm and xi-potential of -41.2+/-1.3 mV. The active components remained stable in the optimized SNEDDS stored at 25 degrees C for at least 12 months. Following oral administration of ZTO-SNEDDS in rats, both AUC and C(max) of germacrone (GM), a representative bioactive marker of ZTO, increased by 1.7-fold and 2.5-fold respectively compared with the unformulated ZTO. PMID:19732813
Zhao, Yi; Wang, Changguang; Chow, Albert H L; Ren, Ke; Gong, Tao; Zhang, Zhirong; Zheng, Ying
One of the hallmarks of urinary tract infection, a serious global disease, is its tendency to recur. Uropathogenic bacteria can invade cells lining the bladder, where they form longer-term intracellular reservoirs shielded from antibiotics, re-emerging at a later date to initiate flare-ups. In these cases, only lengthy systemic antibiotic treatment can eradicate all the reservoirs. Yet, long courses of antibiotics are not ideal, as they can lead to side effects and an increase in antibiotic resistance. Moreover, most antibiotics lose some potency by the time they reach the bladder, and many cannot permeate cells, so they cannot access intracellular reservoirs. Here, using coaxial electrohydrodynamic forming, we developed novel core-shell capsules containing antibiotics as a prototype for a future product that could be infused directly into the bladder. Gentamicin was encapsulated in a polymeric carrier (polymethylsilsesquioxane) and these capsules killed Enterococcus faecalis, a common chronic uropathogen, in vitro in a dose-responsive, slow-release manner. Capsules containing a fluorescent tracer dye in place of gentamicin penetrated human bladder cells and released their dye cargo with no apparent toxicity, confirming their ability to successfully permeate cells. These results suggest that such antibiotic capsules could prove useful in the treatment of recalcitrant UTI. PMID:24068180
Labbaf, Sheyda; Horsley, Harry; Chang, Ming-Wei; Stride, Eleanor; Malone-Lee, James; Edirisinghe, Mohan; Rohn, Jennifer L
The objective of the work was to develop, optimize and evaluate a self-microemulsifying drugdeliverysystem of the poorly water soluble drug, lovastatin. Solubility of lovastatin was determined in various vehicles. Ternary phase diagrams were constructed to identify the efficient self-emulsification region using oils, surfactants, and co-surfactants in aqueous environment. Optimized formulations were assessed for drug content, spectroscopic clarity, emulsification time, contact angle, zeta potential, particle size and dissolution studies. Zeta potential was measured in absence and presence of oleylamine, a positive charge inducer. On the basis of similarity and dissimilarity of particle size distribution, formulations were characterized using principal component analysis and agglomerative hierarchy cluster analysis, the multivariate statistical analysis. Transmission electron microscopy of selected formulations (F5-F7) confirmed the spherical shape of globules with no signs of coalescence of globules and precipitation of drug, even after 24 h post dilution in distilled water. The relevance of differences in t(50%) and percentage dissolution efficiency was evaluated statistically by two-way ANOVA. Infrared spectroscopy, differential scanning calorimetric and x-ray diffraction studies indicated no incompatibility between drug, oil and surfactants. The results of this study indicate that the self-microemulsifying drugdeliverysystem of lovastatin, owing to nanosize, has potential to enhance its absorption and without interaction or incompatibility between the ingredients. PMID:19793039
Many drugs and drug candidates are suboptimal because of short duration of action. For example, peptides and proteins often have serum half-lives of only minutes to hours. One solution to this problem involves conjugation to circulating carriers, such as PEG, that retard kidney filtration and hence increase plasma half-life of the attached drug. We recently reported an approach to half-life extension that uses sets of self-cleaving linkers to attach drugs to macromolecular carriers. The linkers undergo ?-eliminative cleavage to release the native drug with predictable half-lives ranging from a few hours to over 1 y; however, half-life extension becomes limited by the renal elimination rate of the circulating carrier. An approach to overcoming this constraint is to use noncirculating, biodegradable s.c. implants as drug carriers that are stable throughout the duration of drug release. Here, we use ?-eliminative linkers to both tether drugs to and cross-link PEG hydrogels, and demonstrate tunable drug release and hydrogel erosion rates over a very wide range. By using one ?-eliminative linker to tether a drug to the hydrogel, and another ?-eliminative linker with a longer half-life to control polymer degradation, the system can be coordinated to release the drug before the gel undergoes complete erosion. The practical utility is illustrated by a PEG hydrogel–exenatide conjugate that should allow once-a-month administration, and results indicate that the technology may serve as a generic platform for tunable ultralong half-life extension of potent therapeutics.
Ashley, Gary W.; Henise, Jeff; Reid, Ralph; Santi, Daniel V.
Currently available deliverysystems for genetic drugs have limited utility for systemic applications. Cationic liposome/plasmid DNA or oligonucleotide complexes are rapidly cleared from circulation, and the highest levels of activity are observed in 'first pass' organs, such as the lungs, spleen and liver. Engineered viruses can generate an immune response, which compromises transfection resulting from subsequent injections and lack target specificity. A carrier, which can accumulate at sites of diseases such as infections, inflammations and tumours, has to be a small, neutral and highly serum-stable particle, which is not readily recognized by the fixed and free macrophages of the reticuloendothelial system (RES). This review summarizes lipid-based technologies for the delivery of nucleic acid-based drugs and introduces a new class of carrier systems, which solve, at least in part, the conflicting demands of circulation longevity and intracellular delivery. Plasmid DNA and oligonucleotides are entrapped into lipid particles that contain small amounts of a positively charged lipid and are stabilized by the presence of a polythylene glycol (PEG) coating. These carriers protect nucleic acid-based drugs from degradation by nucleases, are on average 70 nm in diameter, achieve long circulation lifetimes and are capable of transfecting cells. PMID:10332748
Maurer, N; Mori, A; Palmer, L; Monck, M A; Mok, K W; Mui, B; Akhong, Q F; Cullis, P R
Microparticle preparation, a new drugdeliverysystem based on microencapsulation technique, includes micro-spheres and microcapsules. Recently, this new drugdeliverysystem has been applied in developing new dosage forms for the traditional Chinese medicine (TCM). TCM microparticles can perform several sound characteristics and functions which are currently unavailable in TCM preparations, such as controlled release, effect of targeting, increasing bioavailability or low toxicity. This makes it possible that TCM may exert much higher therapeutic efficacy and show lower side-effects as well. Although the studies on TCM microparticles are still in the beginning stage, microparticle preparation of TCM has given rise to comprehensive attention and will have a wonderful prospect. The progress in this field is reviewed in this article. PMID:17511135
Background and the purpose of the study Many drugs which have narrow therapeutic window and are absorbed mainly in stomach have been developed as gastroretentive deliverysystem. Rosiglitazone maleate, an anti-diabetic, is highly unstable at basic pH and is extensively absorbed from the stomach. Hence there is a need to develop a gastroretentive system. In this study a superporous hydrogel was developed as a gastroretentive drugdeliverysystem. Methods Chitosan/poly(vinyl alcohol) interpenetrating polymer network type superporous hydrogels were prepared using a gas foaming method employing glyoxal as the crosslinking agent for Rosiglitazone maleate. Sodium bicarbonate was applied as a foaming agent to introduce the porous structure. Swelling behaviors of superporous hydrogel in acidic solution were studied to investigate their applications for gastric retention device. The optimum preparation condition of superporous hydrogels was obtained from the gelation kinetics. FT-IR, scanning electron microscopy, porosity and swelling ratio studies were used to characterize these polymers. In vitro drug release studies were also carried out. Results The introduction of a small amount of Poly(Vinyl Alcohol) enhanced the mechanical strength but slightly reduced the swelling ratio. The prepared superporous hydrogels were highly sensitive to pH of swelling media, and showed reversible swelling and de-swelling behaviors maintaining their mechanical stability. The degradation kinetics in simulated gastric fluid showed that it had biodegradability. Swelling was dependent on the amount of chitosan and crosslinker. The drug release from superporous hydrogels was sustained for 6 hrs. Major Conclusion The studies showed that chitosan-based superporous hydrogels could be used as a gastroretentive drugdeliverysystem for rosiglitazone maleate in view of their swelling and prolonged drug release characteristics in acidic pH.
Image guided technique is playing an increasingly important role in the investigation of the biodistribution and pharmacokinetics of drugs or drugdeliverysystems. The application of these new materials and techniques with combined properties of diagnosis and therapy can benefit the development of targeted drugdeliverysystem and modern personalized medicine This special issue provides an up-to-date collection of original research articles and review on the development of novel targeted drug and drugdeliverysystems combining with non-invasive image guided techniques for chemotherapeutic reagents or DNA delivery.
The purpose of this work was to develop and characterize a novel deliverysystem of post-expansile hydrogel foam aerosol of propylene glycol-embodying liposomes (PG-liposomes) (PEHFL) for vaginal drugdelivery applications. Matrine (MT) was used as a model drug to investigate the vaginal mucous membrane permeation behavior of MT from PEHFL versus PG-liposomes foam aerosol (PLFA), hydrogel foam aerosol (HFA) and hydrogel (HYG). The MT loaded PG-liposomes were characterized for shape, particle size, polydispersity, zeta potential and encapsulation efficiency; the foams of PEHFL were also characterized for swelling behavior, mucoadhesive force and duration. Results revealed that: (i) the MT loaded PG-liposomes had a mean size of 122 ± 16 nm, a good polydispersity index of 0.147 ± 0.023, and exhibited a negative charge of -47.5 ± 0.4 mV, the MT entrapment capacity in PG-liposomes (was calculated as percentages of total drug) was 80.8 ± 2.6%; (ii) the foams of PEHFL had a laggingly swelling process after spurted from a sealed container, and the higher the temperature of the surrounding environment, the greater the degree of swelling, this swelling state of foams would greatly enhance drug spread uniformly in vaginal canal and contact the vaginal walls tightly; (iii) the foams of PEHFL had a mucoadhesive force about 1460 ± 123 mN/cm(2), and could sustain 85 ± 11 min in vitro; (iv) the overall mean permeated MT through unit mass of porcine vaginal tissue from PEHFL was 2.64, 2.34 and 7.59 times higher than that from PLFA, HFA and HYG, respectively (t-test, P<0.05); and the quantity of MT remaining in the vaginal tissue at the end of the 12h experiment was also significantly greater (t-test, P<0.05) from the PEHFL than from PLFA, HFA and HYG. All of these results indicate that the main advantages of PEHFL over conventional dosage forms are the ability to enhance the vaginal mucosa permeability of MT, spread uniformly in vaginal canal especially the highly folded epithelial surfaces, prolong the residence time at the site of administration and induce MT delayed release. In conclusion, the PEHFL may be a promising deliverysystem for vaginal delivery of medication. PMID:22705561
Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Among the approaches explored so far in order to optimize the transport of these macromolecules across mucosal barriers, the use of nanoparticulate carriers represents a challenging but promising strategy. The present paper aims to compare the characteristics and potential of nanostructures based on the mucoadhesive polysaccharide chitosan (CS). These are CS nanoparticles, CS-coated oil nanodroplets (nanocapsules) and CS-coated lipid nanoparticles. The characteristics and behavior of CS nanoparticles and CS-coated lipid nanoparticles already reported [A. Vila, A. Sanchez, M. Tobio, P. Calvo, M.J. Alonso, Design of biodegradable particles for protein delivery, J. Control. Rel. 78 (2002) 15-24; R. Fernandez-Urrusuno, P. Calvo, C. Remunan-Lopez, J.L. Vila-Jato, M.J. Alonso, Enhancement of nasal absorption of insulin using chitosan nanoparticles, Pharm. Res. 16 (1999) 1576-1581; M. Garcia-Fuentes, D. Torres, M.J. Alonso, New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin (submitted for publication).] are compared with those of CS nanocapsules originally reported here. The three types of systems have a size in the nanometer range and a positive zeta potential that was attributed to the presence of CS on their surface. They showed an important capacity for the association of peptides such as insulin, salmon calcitonin and proteins, such as tetanus toxoid. Their mechanism of interaction with epithelia was investigated using the Caco-2 model cell line. The results showed that CS-coated systems caused a concentration-dependent reduction in the transepithelial resistance of the cell monolayer. Moreover, within the range of concentrations investigated, these systems were internalized in the monolayer in a concentration-dependent manner. This uptake was slightly enhanced by the presence of the CS coating but, as compared with previously published results [M. Garcia-Fuentes, C. Prego, D. Torres, M.J. Alonso, Triglyceride-chitosan nanostructures for oral calcitonin delivery: evaluation in the Caco-2 cell model and in vivo (submitted for publication)], highly dependent on the nature of the lipid core. Nevertheless, these differences in the uptake of the CS-coated systems (solid lipid core or oily core) by the Caco-2 cells did not have a consequence in the in vivo behaviour. Indeed, both CS-coated systems (nanocapsules and CS-coated nanoparticles) showed an important capacity to enhance the intestinal absorption of the model peptide, salmon calcitonin, as shown by the important and long-lasting decrease in the calcemia levels observed in rats. PMID:15588901
Novel targeted proapoptotic anticancer drugdeliverysystems were developed and evaluated. Poly(ethyleneglycol) (PEG) conjugates were used as carriers. Camptothecin (CPT) was used as an anticancer agent–apoptosis inductor. Two types of molecular targets were investigated: (1) an extracellular membrane receptor specific to ovarian cancer and (2) intracellular controlling mechanisms of apoptosis. Synthetic peptides similar to luteinizing hormone-releasing hormone (LHRH) and BCL-2
S. S Dharap; B Qiu; G. C Williams; P Sinko; S Stein; T Minko
This study investigated a novel drugdeliverysystem (DDS), consisting of polycaprolactone (PCL) or polycaprolactone 20% tricalcium phosphate (PCL-TCP) biodegradable scaffolds, fibrin Tisseel sealant and recombinant bone morphogenetic protein-2 (rhBMP-2) for bone regeneration. PCL and PCL-TCP-fibrin composites displayed a loading efficiency of 70% and 43%, respectively. Fluorescence and scanning electron microscopy revealed sparse clumps of rhBMP-2 particles, non-uniformly distributed on
B. Rai; S. H. Teoh; D. W. Hutmacher; T. Cao; K. H. Ho
The purpose of this study was to evaluate the effect of formulation components on the in vitro skin permeation of microemulsion drugdeliverysystem containing fluconazole (FLZ). Lauryl alcohol (LA) was screened as the\\u000a oil phase of microemulsions. The pseudo-ternary phase diagrams for microemulsion regions were constructed using LA as the\\u000a oil, Labrasol (Lab) as the surfactant and ethanol (EtOH)
Mrunali R. Patel; Rashmin B. Patel; Jolly R. Parikh; Ajay B. Solanki; Bharat G. Patel
Self-nanoemulsifying drugdeliverysystem (SNEDDS) containing oil (Phosal 53 MCT), surfactant (Labrasol), and cosurfactant\\u000a (Transcutol-HP or Lutrol-E400) was prepared to enhance solubility and dissolution of lutein. Ternary phase diagram of the\\u000a SNEDDS was constructed to identify the self-emulsifying regions following which the percentage of oil, surfactant, and cosurfactant\\u000a in the SNEDDS were optimized in terms of emulsification time and mean
Self-emulsifying drugdeliverysystems (SEDDSs) represent a possible alternative to traditional oral formulations of lipophilic compounds. In the present study, a lipophilic compound, WIN 54954, was formulated in a medium chain triglyceride oil\\/nonionic surfactant mixture which exhibited self-emulsification under conditions of gentle agitation in an aqueous medium. The efficiency of emulsifi-cation was studied using a laser diffraction sizer to determine
Susan A. Charman; William N. Charman; Mark C. Rogge; Terry D. Wilson; Frank J. Dutko; Colin W. Pouton
Limited aqueous solubility of exemestane leads to high variability in absorption after oral administration. To improve the\\u000a solubility and bioavailability of exemestane, the self-microemulsifying drugdeliverysystem (SMEDDS) was developed. SMEDDS\\u000a comprises of isotropic mixture of natural or synthetic oil, surfactant, and cosurfactant, which, upon dilution with aqueous\\u000a media, spontaneously form fine o\\/w microemulsion with less than 100 nm in droplet
Ajeet K. Singh; Akash Chaurasiya; Anshumali Awasthi; Gautam Mishra; Dinesh Asati; Roop K. Khar; Rama Mukherjee
The aim of the present study was to prepare and evaluate an optimized, self-nanoemulsified drugdeliverysystem of ubiquinone.\\u000a A 3-factor, 3-level Box-Behnken design was used for the optimization procedure with the amounts of Polyoxyl 35 castor oil\\u000a (X1), medium-chain mono- and diglyceride (X2), and lemon oil (X3) as the independent variables. The response variable was the cumulative percentage of
Dipyridamole shows poor and variable bioavailability after oral administration due to pHdependent solubility, low biomembrane\\u000a permeability as well as being a substrate of P-glycoprotein. In order to improve the oral absorption of dipyridamole, a self-microemulsifying\\u000a drugdeliverysystem (SMEDDS) for dipyridamole was prepared and evaluated in vitro and in vivo. The optimum formulation was 18% oleic acid, 12% Labrafac lipophile
The purpose of this research work was to formulate and characterize self-micro emulsifying drugdeliverysystem containing\\u000a exemestane. The solubility of exemestane was determined in various vehicles. Pseudo ternary phase diagram was used to evaluate\\u000a the micro-emulsification existence area. SMEDDS formulations were tested for micro-emulsifying properties, and the resultant\\u000a formulations loaded with exemestane (ME1, ME2, ME3, ME4 and ME5) were
Ajeet K. Singh; Akash Chaurasiya; Manish Singh; Satish C. Upadhyay; Rama Mukherjee; Roop K. Khar
The present work was aimed at formulating a SMEDDS (self-microemulsifying drugdeliverysystem) of fenofibrate and evaluating\\u000a its in vitro and in vivo potential. The solubility of fenofibrate was determined in various vehicles. Pseudoternary phase\\u000a diagrams were used to evaluate the microemulsification existence area, and the release rate of fenofibrate was investigated\\u000a using an in vitro dissolution test. SMEDDS formulations
The ability of self-emulsifying drugdeliverysystems (SEDDS) to improve solubility, dissolution rate and bioavailability\\u000a of a poorly water-soluble calcium channel blocker, nimodipine (NM) was evaluated in the present investigation. Solubility\\u000a of NM in various oils, surfactants and cosurfactants was determined. The influence of the ratio of oil to surfactant + cosurfactant,\\u000a pH of aqueous phase on mean globule size
Recent advances in nanotechology and material science have re-ignited interest in drugdelivery research. Arguably, however, hardly any of the systems developed and strategies proposed are really relevant for shaping the future (clinical) face of the nanomedicine field. Consequently, as outlined in this commentary, instead of making ever more carrier materials, and making nanomedicine both science-fiction and fiction-science, we should try to come up with rational and realistic concepts to make nanomedicines work, in particular in patients.
In this paper, we present a new piezoelectrically actuated valveless micropump for the drugdeliverysystem. A simple fabrication process is based on the deep reactive ion-etching (DRIE), glass etching and the anodical bond. The diffuser\\/nozzle element has the divergence angle of 9.4deg, the width of 0.1 mm for the narrowest part and the length of 1.1 mm. The pressure
\\u000a Different types of medication and drugdeliverysystems that could be used in battlefield situations are compared and discussed.\\u000a Rapidly acting therapies that are easy to administer are required for acute injuries, while prolonged therapy would be needed\\u000a for prophylactic treatments, for example with antimicrobial therapies when exposed to microbiological weapons, or health maintenance\\u000a after the acute phase of treatment
In order to develop a controlled-release oral drugdeliverysystem (DDS) which sustains the plasma acetaminophen (AAP) concentration\\u000a for a certain period of time, microporous membrane-coated tablets were prepared and evaluatedin vitro. Firstly, highly water-soluble core tablets of AAP were prepared with various formulations by wet granulation and compression\\u000a technique. Then the core tablets were coated with polyvinylchloride (PVC) in
Chang-Koo Shim; Ki-Man Kim; Young-Il Kim; Chong-Kook Kim
Thermo-sensitive dendrimers hold promise in various biomedical and pharmaceutical applications due to their stimuli-responsive properties. However, for such systems there are still certain unaddressed issues e.g. the undesired toxicity, immunogenicity and short blood circulation time. PEGylation is a potential approach to solve these above problems. The aims of this study were to engineer PEGylated thermo-sensitive dendritic derivatives and to investigate their temperature sensitivity and drug release behaviour therein. Linear poly(N-isopropylacrylamide) (PNIPAAm) and methoxy poly(ethylene glycol) (MPEG) were attached to the surface of polyamidoamine (PAMAM) dendrimers to generate PAMAM-g-PNIPAAm and PAMAM-g-PNIPAAm-co-PEG. PAMAM-g-PNIPAAm exhibited the lowest critical solution temperature (LCST) of ca. 32°C, whereas PAMAM-g-PNIPAAm-co-PEG showed a LCST of ca. 35°C. Indomethacin was used as a model molecule to examine the drug release profiles from both types of dendritic polymers. Results showed that such thermo-sensitive PAMAM derivatives could manipulate drug release simply by controlling the temperature above or below the LCST. At 37°C a prolonged drug release was obtained for both systems with less than 30% of drug was released over 12 h, whilst the release rate is much faster at 30°C and ca. 90% of drug was released over 12 h. The results obtained suggest that these thermo-sensitive PAMAM derivatives could be potential drugdeliverysystems to achieve controlled drug release. PMID:21316434
The development of controlled release systems for drugdelivery is an area that has generated considerable research interest over the past decade. Biodegradable polymers, which degrade naturally via hydrolysis or enzymatic digestion, have demonstrated great potential for use in the preparation of controlled drugdeliverysystems. Biodegradable polymeric drugdeliverysystems hold several distinct advantages over more conventional oral and inhalation routes, including enhanced site specificity of drugdelivery, reduced side effects, improved patient compliance, and greater overall efficacy. The primary objective of this work was to synthesize biodegradable polyesters based on a locked dimer of dihydroxyacetone (DHA).
The colon targeted drugdelivery has a number of important implications in the field of pharmacotherapy. Oral colon targeted drugdeliverysystems 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 drugdeliverysystems 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 drugdeliverysystems. PMID:21969739
The present investigation comprises the formulation and in vitro evaluation of domperidone loaded transdermal drugdelivery\\u000a system (TDDS) for controlled release. The polymer membranes were prepared using xanthan gum (XG) and sodium alginate (SA)\\u000a by varying the blends compositions viz., 10:0, 8:2, 6:4, 5:5, 4:6, 2:8, and 0:10 (XG\\/SA, wt\\/wt, %). The drug loaded membranes\\u000a were evaluated for thickness, content
Nanodiamonds (NDs), as a new member of the carbon nanoparticles family, have attracted more and more attention in biomedicine recently due to their excellent physical and chemical properties. This paper summarizes the main results from the in vitro and in vivo safety assessments of NDs and reports the application of NDs in the development of drugdeliverysystems. In view of the NDs' characteristics of easy formation of a porous cluster structure in solution, an adsorption model for a variety of functional molecules on the ND clusters is proposed, which provides new ideas for developing a novel smart drug with various features such as sustained-release, targeting, and fluorescence imaging.
\\u000a Transdermal drugdelivery is a validated technology contributing significantly to global pharmaceutical care. Since 1980,\\u000a impressive growth in this field has been observed with many commercial successes; importantly, a new chemical entity was recently\\u000a developed and approved for transdermal administration without having first been given as an injectable or oral dosage form.\\u000a The progress achieved has been based on the
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 deliverysystems 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
The number of ion exchange fibers in development has increased over the last several years. However, few studies have reported the use ion-exchange fibers in drugdeliverysystem. In this study polystyrene nanofiber ion exchangers (PSNIE) were fabricated by electrospinning techniques, crosslinking and sulfonation. The degree of crosslinking and the ion exchange capacity (IEC) were determined. The morphology and diameter of the nanofiber mats were analyzed using scanning electron microscopy (SEM). Five cationic model drugs (dextromethorphan, chlorpheniramine, diphenhydramine, propranolol and salbutamol) were loaded into PSNIE. The loading capacity, release and release kinetics of the exchangers were investigated. PSNIE were successfully prepared by electrospinning and were allowed to crosslink for 10 min, resulting in a maximum IEC of 2.86±0.1 meq/g dry PSNIE. The diameter of the fibers after sulfonation was 464±35 nm. Dextromethorphan provided the highest loading in PSNIE while diphenhydramine gave the highest percentage release in both simulated gastric and intestinal fluid (SGF and SIF). The release kinetics of all drugs in SGF and SIF provided the best fit with the particle diffusion model. Our results showed that the development of a PSNIE-based drugdeliverysystem was successful, and PSNIE were able to control drug release. PMID:23623792
Xanthan gum is a high molecular weight natural polysaccharide produced by fermentation process. It consists of 1, 4-linked ?-D-glucose residues, having a trisaccharide side chain attached to alternate D-glucosyl residues. Although the gum has many properties desirable for drugdelivery, its practical use is mainly confined to the unmodified forms due to slow dissolution and substantial swelling in biological fluids. Xanthan gum has been chemically modified by conventional chemical methods like carboxymethylation, and grafting such as free radical, microwave-assisted, chemoenzymatic and plasma assisted chemical grafting to alter physicochemical properties for a wide spectrum of biological applications. This article reviews various techniques utilized for modification of xanthan gum and its applications in a range of drugdeliverysystems. PMID:23607638
General aspects of biodegradable microspheres prepared from natural and synthesized polymers used in drugdeliverysystems are reviewed first from various viewpoints: characteristics of biodegradable polymers (physicochemical properties, bioerosion mechanism, biocompatibility), preparation method for the microspheres, drug release from parenteral products and briefly nonparenteral products. The relationship between release pattern and pharmacological activity of therapeutic peptides and proteins and rational controlled release design are also discussed. In the latter half, successful sustained release depot formulations of peptides, leuprorelin acetate, and thyrotropin-releasing hormone (TRH), utilizing poly(lactic acid) (PLA) and poly(lactic/glycolic acid) (PLGA) microspheres are reviewed with respect to preparation, drug release, biocompatibility, pharmacological effects, and results of clinical studies. Thereafter, studies on antitumor therapy by chemoembolization using PLGA microspheres containing an angiogenesis inhibitor (TNP-470) are described as an example of targeted drugdelivery with biodegradable microspheres. PMID:8521523
The purpose of this review is to discuss and summarize some of the interesting findings and applications of cyclodextrins\\u000a (CDs) and their derivatives in different areas of drugdelivery, particularly in protein and peptide drugdelivery and gene\\u000a delivery. The article highlights important CD applications in the design of various novel deliverysystems like liposomes,\\u000a microspheres, microcapsules, and nanoparticles. In
Rajeswari Challa; Alka Ahuja; Javed Ali; R. K. Khar
Water-in-oil-in-water (w/o/w) double emulsions are potential for enhancing oral bioavailability of drugs with high solubility and low permeability, but their industrial application is limited due to the instability. Herein, we developed a novel formulation, self-double-emulsifying drugdeliverysystems (SDEDDS) by formulating mixtures of hydrophilic surfactants and water-in-oil (w/o) emulsions, which were easier to be stable through formulations optimization. SDEDDS can spontaneously emulsify to water-in-oil-in-water (w/o/w) double emulsions in the mixed aqueous gastrointestinal environment, with drugs encapsulated in the internal water phase of the double emulsions. We employed SDEDDS to improve the oral absorption of pidotimod, a peptide-like drug with high solubility and low permeability. The optimized pidotimod-SDEDDS were found to be stable up to 6 months under 25°C. Plasma concentration-time profiles from pharmacokinetic studies in rats dosed with SDEDDS showed 2.56-fold (p<0.05) increased absorption of pidotimod, compared to the pidotimod solution. Histopathologic studies confirmed that SDEDDS exerted absorption promoting effect without serious local damages. These studies demonstrate that SDEDDS may be a promising strategy for peroral delivery of peptide and peptidomimetic drugs. PMID:21356300
Qi, Xiaole; Wang, Lishuang; Zhu, Jiabi; Hu, Zhenyi; Zhang, Jie
Star polymers have unique characteristics due to their well-defined size and tailor ability which makes these polymers attractive candidates as carriers in drugdeliverysystem applications. This work focuses on attaching a drug to the star polymer (polyamidoamine). The conjugation of polyamidoamine (PAMAM, generation 4) with methotrexate (MTX) (model drug) was studied in which monomethyl polyethylene glycol (MPEG) was used as a linker to reduce the toxicity of dendrimer. Conjugation starts with attaching the drug to the linker and followed by further conjugation with the polyamidoamine (PAMAM) dendrimer. The conjugation of PAMAM-PEG-MTX was confirmed through UV-Vis, FTIR, 1H NMR and DSC. The loading capacities and release profile of this conjugate were determined using 1H NMR and UV spectrometer.
A simple but very effective sample preparation method is discussed for a matrix or drug-in-adhesive type of transdermal drugdeliverysystem (TDS). The method is a one-step extraction using a methanol\\/water solvent system. Because of the unique design and physical property of the deliverysystem, special considerations were taken in selection of sample solvent, sample container and extraction enhancement device.
Weiyong Li; David Nadig; Henrik T. Rasmussen; Kudan Patel; Tridarsh Shah
The distinguishable films composed of poly(vinyl alcohol) (PVA) and carboxymethyl-chitosan (CMCS) were prepared by blending/casting method, and loaded with ornidazole (OD) as local drugdeliverysystem. In vitro test, the blend films showed pH-responsive swelling behavior and moderate drug release action, and also exhibited a little antimicrobial activity against E. coli and S. aureus strains. Those characteristics of CMCS/PVA blend films were essentially governed by the weight ratio of CMCS and PVA. Increasing the content of PVA in blend film would decrease swelling and decelerated the drug release. However, increasing the content of CMCS would enhance the antimicrobial activity. The biocompatibility and bioactivity of the blend film were also evaluated using rabbit blood and Wister rats. This blend drugsystem was of no hemolysis, no toxicity to rat periodontia and no cytotoxicity to the rat muscle. After subcutaneously implanting the blend drug films in Wister rat, the systems kept a good retention at the application site and maintained high drug concentration in long time (5 days) which was longer than the period of drug released in vitro (160 min). PMID:17268861
Nasal mucosa offers advantages to deliver drugs to brain via olfactory route thus provides rapid onset of drug action and hence faster therapeutic effect. Therefore, various strategies have been proposed to improve the delivery of different drugs to brain including liposomes, colloidal drug carriers, micelles, chimeric peptide technology and nanotechnology through nasal route. The low blood level of folates is the primary cause of depression in Alzheimer's disease. Folic acid is a water soluble vitamin showing difficulty in crossing the blood brain barrier and thus was formulated as niosomal nasal drugdeliverysystems to target the brain. In the present work, folic acid niosomes were prepared using different nonionic surfactants i.e., span 20, span 60, span 80, tween 20, tween 80 and cholesterol by using lipid layer hydration technique. These were evaluated for particle size, viscosity, osmotic shock, entrapment efficiency and in vitro drug release. The influence of different formulation variables such as surfactant type, surfactant concentration, and cholesterol concentration was optimized for required size distribution, viscosity, entrapment efficiency and in vitro release. The prepared niosomes were in the size range of 3.05-5.625µm. Niosomes prepared with span 60 and cholesterol in the ratio of 1:1(50mg: 50mg) shown higher entrapment efficiency of 69.42% and better in vitro drug release of 64.2% at the end of 12 hrs and therefore considered as optimized formulation. The stability studies were carried out by storing niosomes at 4±1°C and 25±1°C and showed good stability over the period of storage. The release of drug from niosomes followed anomalous diffusion and obeyed first order release kinetics. Ex-vivo perfusion studies were also performed by using rat model, about 48.15% of drug was found to be absorbed through nasal cavity at the end of 6 hrs. PMID:23863098
Ravouru, Nagaraju; Kondreddy, Pallavi; Korakanchi, Deepthy; Haritha, M
An efficient mechanism-based tumor-targeting drugdeliverysystem, based on tumor-specific vitamin-receptor mediated endocytosis, has been developed. The tumor-targeting drugdeliverysystem is a conjugate of a tumor-targeting molecule (biotin: vitamin H or vitamin B-7), a mechanism-based self-immolative linker and a second-generation taxoid (SB-T-1214) as the cytotoxic agent. This conjugate (1) is designed to be (i) specific to the vitamin receptors overexpressed on tumor cell surface and (ii) internalized efficiently through receptor-mediated endocytosis, followed by smooth drug release via glutathione-triggered self-immolation of the linker. In order to monitor and validate the sequence of events hypothesized, i.e., receptor-mediated endocytosis of the conjugate, drug release, and drug-binding to the target protein (microtubules), three fluorescent/fluorogenic molecular probes (2, 3, and 4) were designed and synthesized. The actual occurrence of these processes was unambiguously confirmed by means of confocal fluorescence microscopy (CFM) and flow cytometry using L1210FR leukemia cells, overexpressing biotin receptors. The molecular probe 4, bearing the taxoid linked to fluorescein, was also used to examine the cell specificity (i.e., efficacy of receptor-based cell targeting) for three cell lines, L1210FR (biotin receptors overexpressed), L1210 (biotin receptors not overexpressed), and WI38 (normal human lung fibroblast, biotin receptor negative). As anticipated, the molecular probe 4 exhibited high specificity only to L1210FR. To confirm the direct correlation between the cell-specific drugdelivery and anticancer activity of the probe 4, its cytotoxicity against these three cell lines was also examined. The results clearly showed a good correlation between the two methods. In the same manner, excellent cell-specific cytotoxicity of the conjugate 1 (without fluorescein attachment to the taxoid) against the same three cell lines was confirmed. This mechanism-based tumor-targeting drugdeliverysystem will find a range of applications. PMID:20429547
Luminescence functionalization of ordered mesoporous MCM-41 silica was realized by depositing a YVO4:Eu3+ phosphor layer on its surface via the Pechini sol-gel process. This material, which combines the mesoporous structure of MCM-41 and the strong red luminescence property of YVO4:Eu3+, has been studied as a host carrier for drugdelivery/release systems. The structure, morphology, texture and optical properties of the materials were well characterized by x-ray diffraction (XRD), Fourier infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), N2 adsorption and photoluminescence (PL) spectra. The results indicated that the specific surface area and pore volume of MCM-41, which were directly correlated to the drug-loading amount and ibuprofen (IBU) release rate, decreased in sequence after deposition of YVO4:Eu3+ and loading of IBU as expected. The IBU-loaded YVO4:Eu3+@MCM-41 system still showed red luminescence under UV irradiation (365 nm) and a controlled release property for IBU. In addition, the emission intensity of Eu3+ increases with an increase in the cumulative released amount of IBU, making the extent of drug release easily identified, tracked and monitored by the change of luminescence, which demonstrates its potential application in drugdelivery/release systems.
Objective Systemic steroid injections are used to treat idiopathic sudden-onset sensorineural hearing loss (ISSHL) and some inner ear disorders. Recent studies show that transtympanic (TT) steroid injections are effective for treating ISSHL. As in vivo monitoring of drugdelivery dynamics for inner ear is lacking, its time course and dispersion of drugs is unknown. Here, we used a new in vivo imaging system to monitor drugdelivery in live mice and to compare drug concentrations over time after TT and systemic injections. Methods Luciferin delivered into the inner ears of GFAP-Luc transgenic mice reacted with luciferase in GFAP-expressing cells in the cochlear spiral ganglion, resulting in photon bioluminescence. We used the Xenogen IVIS® imaging system to measure how long photons continued to be emitted in the inner ear after TT or systemic injections of luciferin, and then compared the associated drug dynamics. Results The response to TT and IP injections differed significantly. Photons were detected five minutes after TT injection, peaking at ?20 minutes. By contrast, photons were first detected 30 minutes after i.p. injection. TT and i.p. drugdelivery time differed considerably. With TT injections, photons were detected earlier than with IP injections. Photon bioluminescence also disappeared sooner. Delivery time varied with TT injections. Conclusions We speculate that the drug might enter the Eustachian tube from the middle ear. We conclude that inner-ear drug concentration can be maintained longer if the two injection routes are combined. As the size of luciferin differs from that of therapeutics like dexamethasone, combining drugs with luciferin may advance our understanding of in vivo drugdelivery dynamics in the inner ear.
The purpose of this research work was to develop and evaluate a chronotherapeutic based colon-targeted drugdeliverysystem of theophylline (THEO) exploiting pH-enzyme sensitive property for the prevention of episodic attack of asthma in early morning. Guar gum microspheres of theophylline were prepared by emulsification technique. Coating of microspheres was performed using solvent evaporation method with pH sensitive Eudragit(®) polymers. The particle size and surface morphology, entrapment efficiency and degree of swelling of microspheres were examined. The in vitro drug release studies were performed in pH progression medium and also in the presence of 2% rat caecal content. Theophylline was efficiently microencapsulated in guar gum microspheres at different polymer concentrations (1-4%). Fourier transform infrared (FT-IR)-spectroscopy confirmed the intermolecular interactions between guar gum and glutaraldehyde. Coating of guar gum microspheres by Eudragit led to decelerate the in vitro drug release of THEO. Moreover in vitro drug release studies also performed with 2% rat caecal content showed marked increment in drug release. The controlled release of THEO after a lag time was achieved with developed formulation for chronotherapeutic delivery. The pH dependent solubility behavior of Eudragit and gelling properties of guar gum are found to be responsible for delaying the release. PMID:21297298
Fluorescence nanocrystals or quantum dots (QDs) are engineered nanoparticles (NP) that have shown great promise with potential for many biological and biomedical applications, especially in drugdelivery/activation and cellular imaging. The use of nanotechnology in medicine directed to drugdelivery is set to expand in the coming years. However, it is unclear whether QDs, which are defined as NPs rather than small molecules, can specifically and effectively deliver drugs to molecular targets at subcellular levels. When QDs are linked to suitable ligands that are site specific, it has been shown to be brighter and photostable when compared with organic dyes. Interestingly, pharmaceutical sciences are exploiting NPs to minimize toxicity and undesirable side effects of drugs. The unforeseen hazardous properties of the carrier NPs themselves have given rise to some concern in a clinical setting. The kind of hazards encountered with this new nanotechnology materials are complex compared with conventional limitations created by traditional deliverysystems. The development of cadmium-derived QDs shows great potential for treatment and diagnosis of cancer and site-directed delivery by virtue of their size-tunable fluorescence and with highly customizable surface for directing their bioactivity and targeting. However, data regarding the pharmacokinetic and toxicology studies require further investigation and development, and it poses great difficulties to ascertain the risks associated with this new technology. Additionally, nanotechnology also displays yet another inherent risk for toxic cadmium, which will enter as a new form of hazard in the biomedical field. This review will look at cadmium-derived QDs and discuss their future and their possible toxicities in a disease situation. PMID:20964619
Ghaderi, Shirin; Ramesh, Bala; Seifalian, Alexander M
A drug-loaded tumor cell (DLTC) system has been developed for lung metastasis-targeting drugdelivery. Doxorubicin was loaded into B16-F10 murine melanoma cells (96 microg/10(6) cells). The loading process led to the death of all the carrier cells. The diameter of DLTC was 15.03+/-2.36 microm (mean +/- SD). The amount and rate of doxorubicin being released from the DLTC mainly depended on the drug loading and carrier cell concentration. Over a 6-month storage in phosphate buffered saline (PBS) at 4 degrees C, the decrease in intracellular drug concentration and the carrier cell number were less than 25% and 5%, respectively. After a bolus injection of 30 microg doxorubicin in either DLTC form or free solution into the mice tail veins, drug deposit in the lung from DLTC was 3.6-fold of that achieved by free drug solution. The latter resulted in higher drug content in liver and spleen. Extensive trypsinization of DLTC reduced its lung targeting effect by 30%, and the density of surface adhesion molecule GM3 on DLTC surface by 25%. In conclusion, this DLTC system demonstrated a lung-targeting activity that may be partially attributed to its specific surface characteristics. PMID:11400864
Shao, J; DeHaven, J; Lamm, D; Weissman, D N; Runyan, K; Malanga, C J; Rojanasakul, Y; Ma, J K
Drugdelivery technology has brought additional benefits to pharmaceuticals such as reduction in dosing frequency and side effects, as well as the extension of patient life. To address this need, cochleates, a precipitate obtained as a result of the interaction between phosphatidylserine and calcium, have been developed and proved to have potential in encapsulating and delivering small molecule drugs. This chapter discusses the molecules that can be encapsulated in a cochleate system and describes in detail the methodology that can be used to encapsulate and characterize hydrophobic drugs such as amphotericin B, a potent antifungal agent. Some efficacy data in animal models infected with candidiasis or aspergillosis are described as well. PMID:15721389
The practical application of genistein as a low toxicity chemotherapeutic drug is hindered by many of its in vivo properties. To overcome these obstacles, a new multifunctional drugdeliverysystem is developed, which is based on covalently attaching genistein onto Fe3O4 nanoparticles coated by cross-linked carboxymethylated chitosan (CMCH). The structure of the Fe3O4-CMCH-genistein nano-conjugate was confirmed by transmission electron micrographs (TEM), X-ray diffraction (XRD) and Fourier-transfer infrared (FT-IR) spectroscopy. The nano-conjugate shows good water solubility and superparamagnetic properties with a saturation magnetization of 55.1 emu/g. The effects of free genistein and FeO4-CMCH-genistein nano-conjugate on the proliferation and apoptosis of gastric cancer cell line SGC-7901 were investigated by MTT assay and flow cytometry (FACS). MTT results indicate that the Fe3O4-CMCH-genistein nano-conjugate exhibits a significantly enhanced inhibition effect to the SGC-7901 cancer cells than the free genistein. FACS data suggests that the inhibition on cell proliferation of the nano-conjugate is related with an induced apoptosis process. This drugdeliverysystem is promising for future multifunctional chemotherapeutic application that combines drug release and magnetic hyperthermia therapy. PMID:20355429
Our laboratories have been working together in close collaboration for over 10 years concerning the design and performance of lipid-based drugdeliverysystems. Over the past 3 years we have conceived of, developed, and tested pre-clinically, a new liposome-based temperature-sensitive drugdeliverysystem for the treatment of solid tumors. This work is reported in a series of four publications: ‘J.
A preliminary evaluation was carried out on metronidazole-loaded Self Emulsifying DrugDeliverySystem (SEDDS) using two vegetable oils-Palm Kernel Oil (PKO) and Palm Oil (PO). Purification of oils, drug solubility in the oils, pre/post formulation isotropicity tests, emulsification times and release studies of metronidazole from the SEDDS were carried out. Results indicated solubility values of 4.441 and 4.654%w/w, respectively for metronidazole in PKO and PO. Preformulation isotropicity test revealed that out of the 24 batches evaluated 10 of the SEDDS formulations containing different oil: surfactant ratios and PKO:PO admixtures were found to be isotropic after 5 h. However when the SEDDS were loaded with metronidazole there was a reduction in the number (to 7) of formulations that maintained isotropicity and stability after 72 h. All the batches had emulsification times of less than two minutes except batch 4D with oil:surfactant concentration of 50:50. The release profile showed that most of the formulations released 50% of drug in less than 8 min and 85% of drug in less than 30 min. We therefore conclude that SEDDS containing the two vegetable oils are potential alternatives when immediate release and delivery of metronidazole is the primary motivation.
Transdermal drugdelivery offers an attractive alternative to the conventional drugdelivery 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
Drugdelivery to the brain poses unique challenges. Specialized anatomic and physiological features of the cerebrovasculature and cerebral tissue fluids result in barriers which significantly restrict delivery of a wide range of possible therapeutic agents. In addition to these normal restrictions to brain drugdelivery, pathophysiological features and sequelae of acute brain injury will also impact upon the efficiency of
Eng H. Lo; Aneesh B. Singhal; Vladimir P. Torchilin; N. Joan Abbott
Purpose: The aim of this in vitro study was to compare different catheter systems for local drugdelivery with respect to the penetration\\u000a depth of a biotin marker solution delivered into the vessel wall.\\u000a \\u000a \\u000a \\u000a \\u000a Methods: Post-mortem carotid arteries from pigs were locally infused with a biotin solution using three different catheter systems.\\u000a With all catheters (microporous balloon catheter, hydrogel-coated balloon
Heiko Alfke; Hans-Joachim Wagner; Christian Calmer; Klaus Jochen Klose
Purpose: The aim of this in vitro study was to compare different catheter systems for local drugdelivery with respect to the penetration depth of a biotin marker solution delivered into the vessel wall. Methods: Post-mortem carotid arteries from pigs were locally infused with a biotin solution using three different catheter systems. With all catheters (microporous balloon catheter, hydrogel-coated balloon catheter, and spiral balloon catheter) we used the same pressure of 405 kPa (4 atm) and infusion times of 60, 90, and 300 sec. After infusion the arteries were histologically prepared and stained using a biotin-specific method. With a light microscope an observer, blinded to the catheter type, scored the amount of biotin within the vessel wall, measured as staining intensity, and the penetration depth of the biotin. Results: Delivery with the hydrogel-coated balloon catheter was limited to the intima and the innermost parts of the media. The spiral balloon and microporous balloon catheter showed both a deeper penetration and a larger amount of delivered biotin compared with the hydrogel catheter, with a slightly deeper penetration using the microporous catheter. The penetration depth showed a correlation with infusion time for the spiral balloon and microporous catheters, but not for the hydrogel-coated catheter. Conclusion: Different catheter designs lead to different patterns of local drugdelivery. The differences in penetration depth and amount of the substance delivered to the vessel wall should be known and might be useful for targeting specific areas within the vessel wall.
Alfke, Heiko; Wagner, Hans-Joachim; Calmer, Christian; Klose, Klaus Jochen [Department of Diagnostic Radiology, University Hospital, Baldingerstrasse, D-35033 Marburg (Germany)
The multifactorial pathological progress of spinal cord injury (SCI) is probably the main reason behind the absence of efficient therapeutic approaches. Hence, very recent highlights suggest the use of new multidrug deliverysystems capable of local controlled release of therapeutic agents. In this work, a biocompatible hydrogel-based system was developed as multiple drugdelivery tool, specifically designed for SCI repair strategies. Multiple release profiles were achieved by loading gel with a combination of low and high steric hindrance molecules. In vitro, in vivo and ex vivo release studies showed an independent combination of fast diffusion-controlled kinetics for smaller molecules together with slow diffusion-controlled kinetics for bigger ones. A preserved functionality of loaded substances was always achieved, confirming the absence of any chemical stable interactions between gel matrix and loaded molecules. Moreover, the relevant effect of the cerebrospinal fluid flux dynamics on the drug diffusion in the spinal cord tissue was here revealed for the first time: an oriented delivery of the released molecules in the spinal cord tract caudally to the gel site is demonstrated, thus suggesting a more efficient gel positioning rostrally to the lesion. PMID:22227024
Amongst the various routes of drugdelivery, the field of ocular drugdelivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. Recent research has focused on the characteristic advantages and limitations of the various drugdeliverysystems, and further research will be required before the ideal system can be developed. Administration of drugs to the ocular region with conventional deliverysystems leads to short contact time of the formulations on the epithelium and fast elimination of drugs. This transient residence time involves poor bioavailability of drugs which can be explained by the tear production, non-productive absorption and impermeability of corneal epithelium. Anatomy of the eye is shortly presented and is connected with ophthalmic delivery and bioavailability of drugs. In the present update on ocular dosage forms, chemical deliverysystems such as prodrugs, the use of cyclodextrins to increase solubility of various drugs, the concept of penetration enhancers and other ocular drugdeliverysystems such as polymeric gels, bioadhesive hydrogels, in-situ forming gels with temperature-, pH-, or osmotically induced gelation, combination of polymers and colloidal systems such as liposomes, niosomes, cubosomes, microemulsions, nanoemulsions and nanoparticles are discussed. Novel ophthalmic deliverysystems propose the use of many excipients to increase the viscosity or the bioadhesion of the product. New formulations like gels or colloidal systems have been tested with numerous active substances by in vitro and in vivo studies. Sustained drug release and increase in drug bioavailability have been obtained, offering the promise of innovation in drugdeliverysystems for ocular administration. Combining different properties of pharmaceutical formulations appears to offer a genuine synergy in bioavailability and sustained release. Promising results are obtained with colloidal systems which present very comfortable conditions of use and prolonged action. PMID:23153114
Poly(vinyl alcohol) was crosslinked with ethylene glycol diglycidyl ether to obtain hydrogel-forming polymers. The polymers were also substituted with oleoyl chloride, providing hydrogels with weak solubility.These new polymeric materials were evaluated for the formulation of sustained drugdeliverysystems. Vancomycin hydrochloride was used as a peptidic model drug whose sustained release should minimize its inactivation in the upper part of the gastrointestinal tract. Spray-dried mixtures of the drug and the polymer [at 1:4 and 1:8 (w:w) ratios] were prepared and the release of the drugs from the mixtures was evaluated in vitro at pH 2.0, 5.5, 7.4, and 8.0. The results indicated that the crosslinked polymers slowed down the release of the drugs with respect to the pure drug at each pH.The degree of crosslinking of ethylene glycol diglycidyl ether and the extent of substitution with oleoyl chloride were found to influence drug release. PMID:12007112
Poly(vinyl alcohol) was crosslinked with ethylene glycol diglycidyl ether to obtain hydrogel-forming polymers. The polymers were also substituted with oleoyl chloride, providing hydrogels with weak solubility. These new polymeric materials were evaluated for the formulation of sustained drugdeliverysystems. Vancomycin hydrochloride was used as a peptidic model drug whose sustained release should minimize its inactivation in the upper part of the gastrointestinal tract. Spray-dried mixtures of the drug and the polymer [at 1:4 and 1:8 (w:w) ratios] were prepared and the release of the drugs from the mixtures was evaluated in vitro at pH 2.0, 5.5, 7.4, and 8.0. The results indicated that the crosslinked polymers slowed down the release of the drugs with respect to the pure drug at each pH. The degree of crosslinking of ethylene glycol diglycidyl ether and the extent of substitution with oleoyl chloride were found to influence drug release. PMID:12043460
The objective of our investigation was to design a self-microemulsifying drug-deliverysystem (SMEDDS) to improve the bioavailability of probucol. SMEDDS was composed of probucol, olive oil, Lauroglycol FCC, Cremophor EL, Tween-80, and PEG-400. Droplet sizes were determined. In vitro release was investigated. Pharmacokinetics and bioavailability of probucol suspension, oil solution, and SMEDDS were evaluated and compared in rats. Plasma drug concentration was determined by high-performance liquid chromatography. After administration of probucol suspension, plasma drug concentration was very low. Relative bioavailability of SMEDDS was dramatically enhanced in an average of 2.15- and 10.22-fold that of oil solution and suspension, respectively. It was concluded that bioavailability of probucol was enhanced greatly by SMEDDS. Improved solubility and lymphatic transport may contribute to the enhancement of bioavailability.
Self-microemulsifying drugdeliverysystem (SMEDDS) of lovastatin was aimed at overcoming the problems of poor solubility and bioavailability. The formulation strategy included selection of oil phase based on saturated solubility studies and surfactant and co-surfactant screening on the basis of their emulsification ability. Ternary phase diagrams were constructed to identify the self-emulsifying region. Capryol 90 (20%) as oil, Cremophore RH40 (40%) as surfactant and Transcutol P (40%) as co-surfactant were concluded to be optimized components. The prepared SMEDDS was characterized through its droplet size, zeta potential, emulsification time, rheological determination and transmission electron microscopy. The optimized formulation exhibited 94% in vitro drug release, which was significantly higher than that of the drug solution. In vivo studies using the Triton-induced hyperlipidemia model in Wistar rats revealed considerable reduction in lipid levels compared to pure lovastatin. The study confirmed the potential of lovastatin SMEDDS for oral administration. PMID:23470348
A straightforward method is proposed for the preparation of drug-loaded biocompatible polymer composites based on the freeze drying technique. The solution of poly(vinyl alcohol) (PVA) and metformin hydrochloride (MH) is frozen using liquid nitrogen and the ice crystals are removed by sublimation through freeze drying, which results in the formation of MH-loaded PVA composite. By controlling the PVA concentration in the solution, both MH-loaded PVA fibers and porous products can be obtained. The synthesized MH-loaded PVA composites are characterized with scanning electron microscopy (SEM), powder X-ray diffraction (XRD), Fourier-transformed infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The drug release behavior of the as-prepared products is studied to reveal their potential use in drugdeliverysystem. PMID:22400234
The in vitro digestion of a self nano-emulsifying drugdeliverysystem (SNEDDS) was visualized by cryogenic transmission electron microscopy (Cryo-TEM). The dynamic lipolysis model, simulating the environment of the gastrointestinal tract in fasted conditions, was used for this purpose. The results revealed that micelles are present during the entire lipolysis process. Oil droplets from the self nano-emulsifying drugdeliverysystem are transformed to spherical or elongated unilamellar vesicles as lipolysis progresses. Low numbers of bilamellar and open vesicles were detected. After 50% hydrolysis a decrease in the number of unilamellar vesicles and oil droplets was observed. Furthermore, the electrical properties of the oil droplets were investigated by measuring their zeta-potential values as a function of time. An increase (in absolute values) to the zeta-potential of the hydrolyzing SNEDDS droplets observed versus time implying (binding or incorporation) of the micelles to the surface. The current data emphasize that Cryo-TEM combined with the in vitro dynamic lipolysis model can offer useful information on the formation of the various colloid phases during in vitro digestion of lipid-based formulations. Furthermore, it can provide a better understanding of the in vivo behavior of these systems, as well the solubilization of lipophilic drug compounds, offering new insights for designing and optimizing oral lipid-based formulations and possibly predicting their in vivo behavior. Such methodology can be a useful tool for the strategic development of lipid-based formulations. PMID:17418543
A carboxymethyl derivative of scleroglucan (Scl-CM) with a 65+/-5% carboxylic group degree of derivatization (DD) was recently synthesized and characterized. Aqueous solutions of the polymer underwent to a sharp transition toward a gel like behaviour in the presence of divalent ions such as Ca(+2). Physical hydrogels with different Scl-CM/Ca(+2) ratios were prepared and characterized for their rheological behaviour. Their potential as drugdeliverysystems was also evaluated. To this end three non steroidal anti-inflammatory drugs (NSAIDs) were loaded into the hydrogels obtained with 2% w/v solution of Scl-CM and 0.05 and 0.1 M CaCl(2). The release rate of the drugs was critically related to the salt concentration. By an appropriate combination of the hydrogels prepared using different amounts of salt, it was possible to obtain a system able to release diclofenac with zero-order kinetics. Primary skin irritation tests showed a good biocompatibility of the new polymer, as well as of its hydrogels. These results suggest a potential of the new hydrogels for the development of modified deliverysystems in topical formulations. PMID:19701116
Colon specific drugdelivery has gained increased importance not just for the delivery of drugs for the treatment of local diseases associated with the colon but also as potential site for the systemicdelivery of therapeutic peptide and proteins. To achieve successful colon targeted drugdelivery, a drug needs to be protected from degradation, release and\\/or absorption in the upper
The aim of the present study was to formulate a self-emulsifying drugdeliverysystem of atorvastatin calcium and its characterization including in vitro and in vivo potential. The solubility of atorvastatin calcium was determined in various vehicles such as Captex 355, Captex 355 EP/NF, Ethyl oleate, Capmul MCM, Capmul PG-8, Gelucire 44/14, Tween 80, Tween 20, and PEG 400. Pseudoternary phase diagrams were plotted on the basis of solubility data of drug in various components to evaluate the microemulsification region. Formulation development and screening was carried out based on results obtained from phase diagrams and characteristics of resultant microemulsion. Prepared formulations were tested for microemulsifying properties and evaluated for clarity, precipitation, viscosity determination, drug content and in vitro dissolution. The optimized formulation further evaluated for particle size distribution, zeta potential, stability studies and in vivo potential. In vivo performance of the optimized formulation was evaluated using a Triton-induced hypercholesterolemia model in male Albino Wistar rats. The formulation significantly reduced serum lipid levels as compared with atorvastatin calcium. Thus studies illustrated the potential use for the delivery of hydrophobic drug such as atorvastatin calcium by oral route. PMID:20088679
A supersaturating self-emulsifying drugdeliverysystem (S-SEDDS) was prepared and evaluated for enhanced dissolution of celecoxib (CXB), a poorly water-soluble drug. The selected CXB-dissolved SEDDS formulation consisting 10 % Capryol 90 (oil), 45 % Tween 20 (surfactant), and 45 % Tetraglycol (cosurfactant) had the characteristics of small droplet size and great solubility as 208 nm and 556.7 mg/mL in average, respectively. CXB dissolution from SEDDS in simulated gastric fluid was increased to about 20 % for the initial period of 5 min, but decreased to a half level as time elapsed. Thus, precipitation inhibitors were screened to stabilize the supersaturation. The stabilizing effect of Soluplus, an amphiphilic copolymer, was concentration-dependent, revealing the greatest dissolution of approximately 90 % level with delayed drug crystallization by the addition of the copolymer. CXB dissolution from S-SEDDS was pH-independent. We concluded that S-SEDDS formulation would be very useful in the future for developing oral delivery product of poorly water-soluble drugs. PMID:23325487
Song, Woo Heon; Park, Jong Hyeok; Yeom, Dong Woo; Ahn, Byeong Kil; Lee, Kyung Min; Lee, Sang Gon; Woo, Hye Seung; Choi, Young Wook
Xibornol is a lipophilic drug mainly used in Italy and Spain in spray dosage forms for the local treatment of infection and inflammation of the throat. Its poor water solubility makes difficult the development of aqueous formulations of the drug, thus giving rise to a limited number of stable and pharmaceutically accepted preparations. In fact, xibornol is actually marketed only as spray aqueous suspension. The aim of this work was to evaluate the possibility of developing a stable liquid formulation of the drug intended for oral spray administration using a self-microemulsifying drugdeliverysystem (SMEDDS). These systems are able to adequately improve the drug solubility, allowing the introduction of relatively high concentration of drugs in the form of solution. Labrafil M1944, Labrafil M2125 and Labrafac CC were screened as oil phases, Labrasol and Labrafac PG as surfactants and Transcutol as co-surfactant. Pseudo-ternary phase diagrams were constructed, by titration with the aqueous phase of different oil phases and surfactant/co-surfactant mixtures in order to identify the self-microemulsification region and the optimal micro-emulsion composition. Then, complete pharmaceutical formulations were prepared and evaluated for stability and viscosity properties. The final selected formulations, containing Labrafil M1944, Transcutol, Labrafac PG and a hydrophilic co-solvent (propylene glycol or PEG 200) allowed complete solubilization of the required xibornol concentration (3%, w/v) and showed physical good stability up to 2 months at 25 and 4 degrees C, suitable viscosity and organoleptic properties. PMID:17531411
The present study was aimed at designing a microflora triggered colon targeted drugdeliverysystem (MCDDS) based on swellable polysaccharide, Sterculia gum in combination with biodegradable polymers with a view to specifically deliver azathioprine in the colonic region for the treatment of IBD with reduced systemic toxicity. The microflora degradation properties of Sterculia gum was investigated in rat caecal phosphate buffer medium. The polysaccharide tablet cores were coated to different film thicknesses with blends of Eudragit RLPO and chitosan and overcoated with Eudragit L00 to provide acid and intestinal resistance. Swelling and drug release studies were carried out in simulated gastric fluid, SGF (pH 1.2), simulated intestinal fluid, SIF (pH 6.8) and simulated colonic fluid, SCF (pH 7.4 under anaerobic environment), respectively. Drug release study in SCF revealed that swelling force of the Sterculia gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora activated environment. The degradation of chitosan was the rate-limiting factor for drug release in the colon. Drug release from the MCDDS was directly proportional to the concentration of the pore former (chitosan), but inversely related to the Eudragit RLPO coating thickness. PMID:23167303
Albumin, a versatile protein carrier for drugdelivery, has been shown to be nontoxic, non-immunogenic, biocompatible and biodegradable. Therefore, it is ideal material to fabricate nanoparticles for drugdelivery. Albumin nanoparticles have gained considerable attention owing to their high binding capacity of various drugs and being well tolerated without any serious side-effects. The current review embodies an in-depth discussion of
To enhance the solubility and bioavailability of poorly water-soluble Coenzyme Q(10) (CoQ(10)), self-emulsifying drugdeliverysystem (SEDDS) composed of oil, surfactant and cosurfactant for oral administration of CoQ(10) was formulated. The solubility of CoQ(10) was determined in various oils and surfactants. The formulations were prepared using two oils (Labrafil M 1944 and Labrafil M 2125), surfactant (Labrasol) and cosurfactant (Lauroglycol FCC and Capryol 90). In all the formulations, the level of CoQ(10) was fixed at 6% (w/v) of the vehicle. These formulations were characterized by solubility of the drug in the vehicle, particle size of the dispersed emulsion, zeta potential and drug release profile. Ternary phase diagrams were used to evaluate the emulsification domain. The self-emulsification time following introduction into an aqueous medium under gentle agitation was evaluated. The optimized SEDDS formulation consist of 65% (v/v) Labrasol, 25% (v/v) Labrafil M 1944 CS and 10% (v/v) Capryol 90 of each excipient showed minimum mean droplet size (about 240 nm) and optimal drug release profile in water. The pharmacokinetic study in rats for the optimized formulation was performed and compared to powder formulation. SEDDS have significantly increased the C(max) and area under the curve (AUC) of CoQ(10) compared to powder (P<0.05). Thus, this self-micro emulsifying drugdeliverysystem should be an effective oral dosage form for improving oral bioavailability of lipophilic drug, CoQ(10). PMID:19446761
Balakrishnan, Prabagar; Lee, Beom-Jin; Oh, Dong Hoon; Kim, Jong Oh; Lee, Young-Im; Kim, Dae-Duk; Jee, Jun-Pil; Lee, Yong-Bok; Woo, Jong Soo; Yong, Chul Soon; Choi, Han-Gon
Self Microemulsifying DrugDeliverySystems (SMEDDS) are a novel alternative to the conventional transdermal deliverysystems. SMEDDS are water-free systems, made up of oils and surfactants that can readily form a microemulsion upon dilution within an aqueous medium. Before SMEDDS can be used as a drugdeliverysystem it is necessary to investigate the internal microstructure of the resulting microemulsion. Novel Imwitor 308 based SMEDDS were prepared and investigated. Phase behaviour of the comprising components was investigated through the construction of pseudoternary phase diagrams. The formed systems were characterized using visual inspection, measurement of electrical conductivity, viscosity and droplet size. Amongst the pseudoternary systems investigated, IPM/Cremophor EL (50% w/w)/Imwitor (50% w/w) and Myritol 318/Tween 85 (64% w/w)/ Transcutol P (20% w/w)/Imwitor (16% w/w) possessed the largest microemulsion area. Electrical conductivity and viscosity studies depict structural transitions from w/o microemulsion to bicontinuous or o/w microemulsion around 20-35% water. This was further supported by the droplet size and Fourier transform (FT)-IR measurements. The FT-IR data suggests that below the percolation threshold (?(C)) the water molecules are mainly bounded to the surfactant head group (bound water). Above this value, water molecule move to the outer phase of the microemulsion mainly interacting with each other though hydrogen bounding (free water). It was also found that pseudoternary systems with water content of less than 30% were stable at 32°C. Such systems may form stable microemulsion upon contact with the skin. Absorption of water may also result in a supersaturated solution with enhanced transdermal flux. PMID:20930400
For decades, researchers and medical professionals have aspired to develop mechanisms for noninvasive treatment and monitoring of pathological conditions within the human body. The emergence of nanotechnology has spawned new opportunities for novel drugdelivery vehicles capable of concomitant detection, monitoring, and localized treatment of specific disease sites. In turn, researchers have endeavored to develop an imaging moiety that could be functionalized to seek out specific diseased conditions and could be monitored with conventional clinical imaging modalities. Such nanoscale detection systems have the potential to increase early detection of pathophysiological conditions because they can detect abnormal cells before they even develop into diseased tissue or tumors. Ideally, once the diseased cells are detected, clinicians would like to treat those cells simultaneously. This idea led to the concept of multifunctional carriers that could target, detect, and treat diseased cells. The term "theranostics" has been created to describe this promising area of research that focuses on the combination of diagnostic detection agents with therapeutic drugdelivery carriers. Targeted theranostic nanocarriers offer an attractive improvement to disease treatment because of their ability to execute simultaneous functions at targeted diseased sites. Research efforts in the field of theranostics encompass a broad variety of drugdelivery vehicles, imaging contrast agents, and targeting modalities for the development of an all-in-one, localized detection and treatment system. Nanotheranostic systems that utilize metallic or magnetic imaging nanoparticles can also be used as thermal therapeutic systems. This Account explores recent advances in the field of nanotheranostics and the various fundamental components of an effective theranostic carrier. PMID:21932809
Caldorera-Moore, Mary E; Liechty, William B; Peppas, Nicholas A
Self-emulsifying drugdeliverysystems (SEDDS) are complex mixtures in which drug quantification can become a challenging task. Thus, a general need is given for novel analytical methods and a particular interest lies in those techniques with the potential for process monitoring. This article aims to compare Raman spectroscopy with high-resolution ultrasonic resonator technology (URT) for drug quantification in SEDDS. Herein
Drugs used in disease treatment can cause damage to both malignant and normal tissue. This toxicity limits the maximum therapeutic dose. Drug targeting is of high interest to increase the therapeutic efficacy of the drug without increasing systemic toxicity. Certain tissue abnormalities, disease processes, cancers, and infections are characterized by high levels of activity of specific extracellular and/or intracellular proteases. Abnormally high activity levels of specific proteases are present at sites of physical or chemical trauma, blood clots, malignant tumors, rheumatoid arthritis, inflammatory bowel disease, gingival disease, glomerulonerphritis, and acute pancreatitis. Abnormal protease activity is suspected in development of liver thrombosis, pulmonary emphysema, atherosclerosis, and muscular dystrophy. Inactiviating disease-associated proteases by the administration of appropriate protease inhibitors has had limited success. Instead, one could use such proteases to target drugs to treat the condition. Protease mediated drugdelivery offers such a possibility. Solubilizing groups are attached to insoluble drugs via a polypeptide chain which is specifically cleavable by certian proteases. When the solubilized drug enounters the protease, the solubilizing moieties are cleaved, and the drug precipitates at the disease location. Thus, a smaller systemic dosage could result in a therapeutic drug concentration at the treatment site with less systemic toxicity.
Dickson, Eva F.; Goyan, Rebecca L.; Kennedy, James C.; Mackay, M.; Mendes, M. A. K.; Pottier, Roy H.
Traditional Chinese medicine (TCM) is a multi-component complex system and its research must consider its components characteristics of multi-component, multi-target and multi-effect. According to the whole concept of Chinese medicine, also combining with the status quo of Chinese drugs pharmaceutics and setting the material basis component as the premise, this study will develope TCM multiple drugdelivery evaluation system, respectively from three aspects, namely in vitro release, in vivo bioavailability and PK-PD. At the same time, we will try to offer the new thoughts of the programly release, so as to provide new strategies and methods for the development of modern Chinese drugdeliverysystems. PMID:23236774
Natural resources are widely used as raw materials by industries. In most cases, abundant byproducts with low economic interest are also generated from agro-industrial supply chains. There are several examples for the rational use of agro-industrial byproducts in nanobiotechnology field aiming for the development of novel products and processes with high value-added. Examples of these raw materials include carapaces, pelages, blood, bagasses, straws, and other byproducts. Molecules from such materials (e.g. chitosan, cellulose, and albumin) are used as scaffolds of unprecedented novel nanostructures. Research efforts comprising a combination of sustainability, nanobiotechnology, and nanomedicine have emerged. One major area of nanobiotechnological research of agro-industrial byproducts is the field of drugdeliverysystems (DDS). Among the main advantages of agro-industrial byproducts used as drug carriers are their abundance; low price; high biocompatibility; good biodegradability; moderate bioresorbability, associated with reduced systemic toxicity or even no toxicity; and often bioactivity. The goal of these efforts include not only the possibility to characterize and manipulate matter on nanoscale, but also to develop sustainable products and processes, including the development of platforms for drug carriers aiming for the treatment of pathologies such as cancer and diabetes. Indeed, there is great hope that the use of agro-industrial byproducts on nanobiotechnology will increase not only agricultural and livestock productivity, but will also contribute to other areas such as the development of DDS with new properties and low production costs; and sustainable environmental management due to the reuse of industrial discharged byproducts. This review will compile current findings on this perspective in drugdelivery describing the challenges and applications of byproducts as building blocks for modern drug carrier systems. PMID:23746200
The Eudragit RL 100 and propylene glycol (PG) membranes with and without cholesteryl oleyl carbonate (COC) were prepared by the solvent casting method to pioneer a novel application of a thermo-sensitive drugdeliverysystem. After that, the properties of these membranes were investigated by thermal, scanning, and porosity studies. Drug permeation studies through all membranes were carried out using salbuthamol sulphate (SBS) at constant temperatures (25°C and 37°C), respectively. The permeability of SBS through the membranes with COC has been shown to be a discontinuous function of temperature, that is, their permeability increased steeply above the phase transition temperature (37°C) of the COC. The thermo-sensitive permeation mechanism for the membranes might be based on the structure change of the membranes caused by the phase transition, so that the membranes could absorb more water. Considering the high biological safety of Eudragit RL 100 and PG membranes with and without COC might be used to develop a novel thermo-sensitive drugdeliverysystem. PMID:22397637
Daunorubicin (DNR) has a broad spectrum of anticancer activity, but is limited in clinical application due to its serious side effects. The aim of this study was to explore a novel “smart” pH-responsive drugdeliverysystem (DDS) based on titanium dioxide (TiO2) nanoparticles for its potential in enabling more intelligent controlled release and enhancing chemotherapeutic efficiency of DNR. DNR was loaded onto TiO2 nanoparticles by forming complexes with transition metal titanium to construct DNR-TiO2 nanocomposites as a DDS. DNR was released from the DDS much more rapidly at pH 5.0 and 6.0 than at pH 7.4, which is a desirable characteristic for tumor-targeted drugdelivery. DNR-TiO2 nanocomposites induced remarkable improvement in anticancer activity, as demonstrated by flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and nuclear 4?,6-diamidino- 2-phenylindole staining. Furthermore, the possible signaling pathway was explored by western blot. For instance, in human leukemia K562 cells, it was demonstrated that DNR-TiO2 nanocomposites increase intracellular concentration of DNR and enhance its anticancer efficiency by inducing apoptosis in a caspase-dependent manner, indicating that DNR-TiO2 nanocomposites could act as an efficient DDS importing DNR into target cancer cells. These findings suggest that “smart” DNR delivery strategy is a promising approach to cancer therapy.
Malignant glioma is a common and severe primary brain tumor with a high recurrence rate and an extremely high mortality rate within 2 years of diagnosis, even when surgical, radiological, and chemotherapeutic interventions are applied. Intravenously administered drugs have limited use because of their adverse systemic effects and poor blood–brain barrier penetration. Here, we combine 2 methods to increase drugdelivery to brain tumors. Focused ultrasound transiently permeabilizes the blood–brain barrier, increasing passive diffusion. Subsequent application of an external magnetic field then actively enhances localization of a chemotherapeutic agent immobilized on a novel magnetic nanoparticle. Combining these techniques significantly improved the delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea to rodent gliomas. Furthermore, the physicochemical properties of the nanoparticles allowed their delivery to be monitored by magnetic resonance imaging (MRI). The resulting suppression of tumor progression without damaging the normal regions of the brain was verified by MRI and histological examination. This noninvasive, reversible technique promises to provide a more effective and tolerable means of tumor treatment, with lower therapeutic doses and concurrent clinical monitoring.
Mesoporous hydroxyapatite was synthesized using F127 and CTAB as templates. Carvedilol was selected as a model drug. Carvedilol in an amorphous state was incorporated in mesoporous hydroxyapatite. Hydroxyapatite had a high drug load efficiency and provided fast release of carvedilol. Hydroxyapatite is a good carrier for the oral delivery of poorly water-soluble drugs.
A multiparticulate dosage form consisting of a hydrophobic core coated with a pH-dependent polymer is proposed for colonic specific delivery of drugs. Different approaches for colon-specific drugdelivery have been studied over the last decade, including prodrugs, polymeric coating using pH-sensitive or bacterial degradable polymers and matrices. In this work, we present a new multiparticulate system to deliver active molecules
Marta Rodr??guez; José L Vila-Jato; Dolores Torres
Formulations that are able to control the release of drug have become an integral part of the pharmaceutical industry. In particular oral drugdelivery has been the focus of pharmaceutical research for many years. This type of drugdelivery has been at the centre of research due to its many benefits over conventional dosage. The focus of this review is on matrix tablets due to their widely use and simplicity of the formulation. This includes the discussion of various types of matrix tablets and factors affecting the drug release from these formulations. The mechanism of drug release from HPMC matrices is also discussed.
No Heading The esophagus as a site for drugdelivery has been much overlooked in comparison to the remainder of the gastrointestinal tract. The low permeability and transient nature of the esophagus means that it is unsuitable for delivery of drugs for systemic action. However, esophageal disorders including fungal infection, cancers, motility dysfunction, and damage due to gastric reflux may
High frequency acoustic waves, analogous to ultrasound, can enhance the delivery of therapeutic compounds into cells. The compounds delivered may be chemotherapeutic drugs, antibiotics, photodynamic drugs or gene therapies. The therapeutic compounds are administered systemically, or preferably locally to the targeted site. Local delivery can be accomplished through a needle, cannula, or through a variety of vascular catheters, depending on
Steven R. Visuri; Heather L. Campbell; Luiz Da Silva
Irbesartan (IRB) is an angiotensin II receptor blocker antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drugdeliverysystem (SNEDDS) to enhance the oral bioavailability of poorly water-soluble IRB. The solubility of IRB in various oils was determined to identify the oil phase of SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsifying region. The optimized SNEDDS formulation contained IRB (75 mg), Cremophor® EL (43.33%), Carbitol® (21.67%) and Capryol® 90 (32%). SNEDDS was further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, dilution, droplet size and zeta potential. The optimized formulation of IRB-loaded SNEDDS exhibited complete in vitro drug release in 15 min as compared with the plain drug, which had a limited dissolution rate. It was also compared with the pure drug solution by oral administration in male Wister rats. The in vivo study exhibited a 7.5-fold increase in the oral bioavailability of IRB from SNEDDS compared with the pure drug solution. These results suggest the potential use of SNEDDS to improve dissolution and oral bioavailability of poorly water-soluble IRB.
Irbesartan (IRB) is an angiotensin II receptor blocker antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drugdeliverysystem (SNEDDS) to enhance the oral bioavailability of poorly water-soluble IRB. The solubility of IRB in various oils was determined to identify the oil phase of SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsifying region. The optimized SNEDDS formulation contained IRB (75 mg), Cremophor(®) EL (43.33%), Carbitol(®) (21.67%) and Capryol(®) 90 (32%). SNEDDS was further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, dilution, droplet size and zeta potential. The optimized formulation of IRB-loaded SNEDDS exhibited complete in vitro drug release in 15 min as compared with the plain drug, which had a limited dissolution rate. It was also compared with the pure drug solution by oral administration in male Wister rats. The in vivo study exhibited a 7.5-fold increase in the oral bioavailability of IRB from SNEDDS compared with the pure drug solution. These results suggest the potential use of SNEDDS to improve dissolution and oral bioavailability of poorly water-soluble IRB. PMID:22171286
The main purpose of this research work was to design an optimized self micro-emulsifying drugdeliverysystem (SMEDDS) to enhance the bioavailability of the poor water soluble drug, astilbin. The solubility of astilbin was evaluated in various vehicles. Pseudoternary phase diagrams were used to select the components and their ranges by evaluating the micro-emulsification area. Central composite design was applied to optimize the properties of the formulation, including particle size, polydispersity index, drug loading capacity and effective intestinal permeability. The optimized SMEDDS characteristics were investigated including the study of factors influencing particle size and showed the stability of microemulsion when varying the pH and volume of diluents. In vitro drug release profile study was performed using the reverse dialysis method where 95% of the drug was released after 4 h. The developed astilbin SMEDDS was subjected to bioavailability studies in beagle dogs by LC-MS and showed a significant enhancement of bioavailability, indicating the possibility of using SMEDDS as possible drug carrier for astilbin. PMID:22026156
Background Iron oxide nanoparticles are of considerable interest because of their use in magnetic recording tape, ferrofluid, magnetic resonance imaging, drugdelivery, and treatment of cancer. The specific morphology of nanoparticles confers an ability to load, carry, and release different types of drugs. Methods and results We synthesized superparamagnetic nanoparticles containing pure iron oxide with a cubic inverse spinal structure. Fourier transform infrared spectra confirmed that these Fe3O4 nanoparticles could be successfully coated with active drug, and thermogravimetric and differential thermogravimetric analyses showed that the thermal stability of iron oxide nanoparticles coated with chitosan and 6-mercaptopurine (FCMP) was markedly enhanced. The synthesized Fe3O4 nanoparticles and the FCMP nanocomposite were generally spherical, with an average diameter of 9 nm and 19 nm, respectively. The release of 6-mercaptopurine from the FCMP nanocomposite was found to be sustained and governed by pseudo-second order kinetics. In order to improve drug loading and release behavior, we prepared a novel nanocomposite (FCMP-D), ie, Fe3O4 nanoparticles containing the same amounts of chitosan and 6-mercaptopurine but using a different solvent for the drug. The results for FCMP-D did not demonstrate “burst release” and the maximum percentage release of 6-mercaptopurine from the FCMP-D nanocomposite reached about 97.7% and 55.4% within approximately 2,500 and 6,300 minutes when exposed to pH 4.8 and pH 7.4 solutions, respectively. By MTT assay, the FCMP nanocomposite was shown not to be toxic to a normal mouse fibroblast cell line. Conclusion Iron oxide coated with chitosan containing 6-mercaptopurine prepared using a coprecipitation method has the potential to be used as a controlled-release formulation. These nanoparticles may serve as an alternative drugdeliverysystem for the treatment of cancer, with the added advantage of sparing healthy surrounding cells and tissue.
Dorniani, Dena; Hussein, Mohd Zobir bin; Kura, Aminu Umar; Fakurazi, Sharida; Shaari, Abdul Halim; Ahmad, Zalinah
The objective of present investigation was to formulate self-microemulsifying drugdeliverysystems (SMEDDS) of tacrolimus\\u000a (FK 506), a poorly water soluble immunosuppressant that exhibits low and erratic bioavailability. Solubility of FK 506 in\\u000a various oils, surfactants cosurfactants and buffers was determined. Phase diagrams were constructed at different ratios of\\u000a surfactant\\/cosurfactant (K\\u000a \\u000a m\\u000a ) to determine microemulsion existence region. The effect
Purpose Active pharmaceutical ingredients (API) in transdermal drugdeliverysystems (TDS) often causes skin irritation such as erythema\\u000a and edema. We have studied a possible approach for the reduction of skin irritation by patch formulations that control the\\u000a rates of skin permeation and elimination of API.\\u000a \\u000a \\u000a \\u000a Methods Loxoprofen (LX-base) was used to induce the skin irritation. The redness value (?a) was evaluated
Lactose-based placebo tablets were coated using various combinations of two methacrylic acid copolymers, Eudragit® L100-55 and Eudragit® S100, by spraying from aqueous systems. The Eudragit® L100-55–Eudragit® S100 combinations (w\\/w) studied were 1:0, 4:1, 3:2, 1:1, 2:3, 1:4, 1:5 and 0:1. The coated tablets were tested in vitro for their suitability for pH dependent colon targeted oral drugdelivery. The same
M. Zahirul I Khan; Željko Prebeg; Nevenka Kurjakovi?
A new type of copolymer membranes was prepared through photosynthesis of mixtures of three different monomers. The membranes present a linear permeation property in clonidine transdermal drugdeliverysystem. Monomers used in the photosynthesis were 2-hydroxy-3-phenoxypropylacrylate, 4-hydroxybutyl acrylate and sec-butyl tiglate. Permeation property of the membranes with different monomer ratios and thickness were investigated. When clonidine concentrations were in 3.0 - 5.0 mg/ml range, membranes showed near zero order permeation rates. An optimized membrane was characterized by FTIR, DSC and SEM. PMID:16815655