Multifunctional hybrid-carbon nanotubes: new horizon in drug delivery and targeting

Carbon nanotubes (CNTs) have emerged as an intriguing nanotechnological tool for numerous biomedical applications including biocompatible modules for the bioactives delivery ascribed to their unique properties, such as greater loading efficiency, biocompatibility, non-immunogenicity, high surface area and photoluminescence, that make them ideal candidate in pharmaceutical and biomedical science. The design of multifunctional hybrid-CNTs for drug delivery and targeting may differ from the conventional drug delivery system. The conventional nanocarriers have few limitations, such as inappropriate availability of surface-chemical functional groups for conjugation, low entrapment/loading efficiency as well as stability as per ICH guidelines with generally regarded as safe (GRAS) prominences. The multifunctional hybrid-CNTs will sparked and open a new door for researchers, scientist of the pharmaceutical and biomedical arena. This review summarizes the vivid aspects of CNTs like characterization, supramolecular chemistry of CNTs–dendrimer, CNTs–nanoparticles, CNTs–quantum dots conjugate for delivery of bioactives, not discussed so far.     

Bacterial biopolymers: From production to applications in biomedicine

Bacterial polymers obtained tremendous attention over the decades owing to its widespread use in biomedical applications. A better understanding on metabolic pathways and development of improved production strategies through metabolic engineering tools to synthesize tailor made polymer materials to meet their applicability in biomedicine. This review focuses on wide range of these biocompatible polymeric materials include polysaccharides, polyesters, polyamides and polyphosphates with wound healing, antioxidant, antitumor, antimicrobial activities. This review focuses on the advantages of various biomaterials to obtain controlled/sustained drug release and tissue engineering applications in biomedical field and the applications of microbial polysaccharides as drugs in pharmaceutical industry. This review describes the most prominent biomedical applications of bacterial biopolymer material as wound healing bandages, drug delivery, tissue engineering, ortho-dental applications and hydrogels. Reviews the future aspects based on economic feasibility and challenges in mass production and downstream processing of biopolymers and its tailor made synthesis to accomplish diverse applications.     

Two faces of carbon nanotube: toxicities and pharmaceutical applications

In the field of nanotechnology, carbon nanotube (CNT) is gaining importance for the delivery of therapeutic agents and diagnosis of diseases. CNT is emerging as an efficient nanocarrier system with cylindrical nanostructure. Due to its nanoscale dimensions, CNTs have a high cell-penetration quality that allows its use in site-specific targeting. Another aspect of the utilization of CNT lies in its hollow structure through which an active moiety can be delivered in a controlled manner via CNTs' nano channels. Despite these positive aspects of CNT, scientists are still working to improve its biocompatibility and solubility and eliminating toxicity in vivo, which are creating problems with the use of CNTs. Therefore, functionalization becomes an important aspect to be studied because it decreases the toxicity of CNTs and make them nonimmunogenic. In this review, different functionalization techniques of CNTs and their biomedical applications-in particular for cancer therapy to date-are reviewed in detail to present the potential of this nanovector.     

Drug delivery systems 5A. Oral drug delivery

The two main advantages of controlled drug delivery systems are: maintenance of therapeutically optimum drug concentrations in the plasma through zero-order release without significant fluctuations; and elimination of the need for frequent single dose administrations. The oral and other therapeutic systems in human use have validated the concept that controlled continuous drug release can minimize the daily dose of a drug required to maintain the required therapeutic effect, while minimizing unwanted pharmacological effects. By minimizing patient intervention, a design feature of therapeutic systems, compliance is automatically enhanced. Oral drug delivery systems, in particular, have required innovation in materials science to provide materials biocompatible during prolonged contact with body tissues, bioengineering to develop drug delivery modules, and clinical pharmacology for elucidation of drug action under conditions of continuous controlled drug administration. Recent work in advanced oral delivery has been primarily focused on liposome technology and the concept that substances that are normally destroyed by the stomach can be protected long enough before they could be absorbed downstream. For cost and patient convenience, oral delivery certainly would be an attractive method. The nature of biologic substances, however, with their unique technical problems, will probably limit greatly those that can be delivered orally. Besides, where delivery rate control is critical, oral delivery, even when possible, would probably be insufficiently precise. Oral delivery would also limit the substance to bloodstream delivery to the disease site. Even so, oral controlled drug delivery systems will likely find primary usefulness in specific carefully controlled therapies and prophylactic situations with due regard for drug interactions. This system represents a potentially very significant therapeutic modality. These delivery systems will find usefulness primarily in certain well-defined and well-controllable areas with due regard for individual patient variations. The purpose of the present article is to review oral controlled-release drug delivery systems, with particular emphasis on the practical aspects of testing and fabricating these systems and the underlying mechanisms by which control over drug release rate is accomplished.     

Challenges in the use of carbon nanotubes for biomedical applications

Carbon nanotubes (CNTs) are considered for use in numerous technological applications, including as biocompatible modules for the delivery of bioactives. However, there are unique properties of CNTs that limit their use as vehicles for various purposes. This review highlights the various challenges to a pharmaceutical scientist while exploring CNTs as bioactive delivery vehicles. The lack of solubility, nonbiodegradability, circulation half-life of 3-3.5 hours, biocompatibility, and immunogenicity limitations of CNTs are discussed in this review. These limitations indicate the need for modifications in order to explore the feasibility of CNTs as delivery vehicles.     

Multifunctional mesoporous silica nanoparticles for combined therapeutic, diagnostic and targeted action in cancer treatment

The main objective in the development of nanomedicine is to obtain delivery platforms for targeted delivery of drugs or imaging agents for improved therapeutic efficacy, reduced side effects and increased diagnostic sensitivity. A (nano)material class that has been recognized for its controllable properties on many levels is ordered mesoporous inorganic materials, typically in the form of amorphous silica (SiO2). Characteristics for this class of materials include mesoscopic order, tunable pore dimensions in the (macro)molecular size range, a high pore volume and surface area, the possibility for selective surface functionality as well as morphology control. The robust but biodegradable ceramic matrix moreover provides shelter for incorporated agents (drugs, proteins, imaging agents, photosensitizers) leaving the outer particle surface free for further modification. The unique features make these materials particularly amenable to modular design, whereby functional moieties and features may be interchanged or combined to produce multifunctional nanodelivery systems combining targeting, diagnostic, and therapeutic actions. This review covers the latest developments related to the use of mesoporous silica nanoparticles (MSNs) as nanocarriers in biomedical applications, with special focus on cancer therapy and diagnostics.     

Carbon nanotubes as functional excipients for nanomedicines: II. Drug delivery and biocompatibility issues

Carbon nanotubes (CNTs) have potential novel application in nanomedicine as biocompatible and supportive substrates, and as pharmaceutical excipients for creating versatile drug delivery systems. In the second part of this two-part review we focus on the application of CNTs as potential drug delivery systems via chemical functionalization of CNTs for exterior binding of therapeutic and biologically relevant molecules, and via encapsulation of these molecules within the inner cavities of CNTs. We review experimental results of CNT-mediated delivery of small molecules, DNA, proteins, and vaccines, and the potential of CNTs as matrices to support and stimulate neural growth. Last, we examine some toxicological and biocompatibility issues related to the use of CNTs as pharmaceutical excipients and discuss attributes that affect toxicity, such as structure (single-walled vs. multi-walled CNTs), length and aspect ratio, surface area, degree of aggregation, extent of oxidation, surface topology, bound functional group(s), and method of manufacturing.     

Mesoporous carbon nanomaterials in drug delivery and biomedical application

Abstract

Recent development of nano-technology provides highly efficient and versatile treatment methods to achieve better therapeutic efficacy and lower side effects of malignant cancer. The exploration of drug delivery systems (DDSs) based on nano-material shows great promise in translating nano-technology to clinical use to benefit patients. As an emerging inorganic nanomaterial, mesoporous carbon nanomaterials (MCNs) possess both the mesoporous structure and the carbonaceous composition, endowing them with superior nature compared with mesoporous silica nanomaterials and other carbon-based materials, such as carbon nanotube, graphene and fullerene. In this review, we highlighted the cutting-edge progress of carbon nanomaterials as drug delivery systems (DDSs), including immediate/sustained drug delivery systems and controlled/targeted drug delivery systems. In addition, several representative biomedical applications of mesoporous carbon such as (1) photo-chemo synergistic therapy; (2) delivery of therapeutic biomolecule and (3) in vivo bioimaging are discussed and integrated. Finally, potential challenges and outlook for future development of mesoporous carbon in biomedical fields have been discussed in detail.     

Photoresponsive hydrogels for biomedical applications

Hydrogels are soft materials composed of a three-dimensional network which contain a high percentage of water similar to body tissue and are therefore regarded as a biocompatible material. Hydrogels have various potential applications in the biomedical field such as drug delivery and as scaffold for tissue engineering. Control over the physical properties of a hydrogel by an external stimulus is highly desirable and is therefore actively studied. Light is a particularly interesting stimulus to manipulate the properties of a hydrogel as it is a remote stimulus that can be controlled spatially and temporally with great ease and convenience. Therefore in recent years photoresponsive hydrogels have been investigated as an emerging biomaterial. Here we will review recent developments and discuss these new materials, and their applications in the biomedical field.     

Cyclodextrin-based supramolecular systems for drug delivery: Recent progress and future perspective

The excellent biocompatibility and unique inclusion capability as well as powerful functionalization capacity of cyclodextrins and their derivatives make them especially attractive for engineering novel functional materials for biomedical applications. There has been increasing interest recently to fabricate supramolecular systems for drug and gene delivery based on cyclodextrin materials. This review focuses on state of the art and recent advances in the construction of cyclodextrin-based assemblies and their applications for controlled drug delivery. First, we introduce cyclodextrin materials utilized for self-assembly. The fabrication technologies of supramolecular systems including nanoplatforms and hydrogels as well as their applications in nanomedicine and pharmaceutical sciences are then highlighted. At the end, the future directions of this field are discussed.     

Recent advances in bioactive 1D and 2D carbon nanomaterials for biomedical applications

One-dimensional (1D) carbon nanotubes (CNTs) and the two-dimensional (2D) graphene represent the most widely studied allotropes of carbon. Due to their unique structural, electrical, mechanical and optical properties, 1D and 2D carbon nanostructures are considered to be leading candidates for numerous applications in biomedical fields, including tissue engineering, drug delivery, bioimaging and biosensors. The biocompatibility and toxicity issues associated with these nanostructures have been a critical impediment for their use in biomedical applications. In this review, we present an overview of the various materials types, properties, functionalization strategies and characterization methods of 1D and 2D carbon nanomaterials and their derivatives in terms of their biomedical applications. In addition, we discuss various factors and mechanisms affecting their toxicity and biocompatibility.     

Therapeutic Particles and Biomaterials Technology Laboratory at the University of Kansas

Novel technologies to enhance therapeutic delivery and biomaterial performance are fundamental to the development of improved products with fewer unwanted side effects. The Therapeutic Particles and Biomaterials Technology Laboratory at The University of Kansas (KS, USA) works at the interface of medicine and engineering to develop novel materials that enhance therapeutic delivery in a variety of biomedical applications. Research areas include aerosol drug delivery, targeted nanoparticles for drug and contrast agent delivery, biomaterials for tissue engineering and polymer therapeutics. The lab works with industry, academia and law firms through a variety of mechanisms such as fee-for-service, contract research and collaboration. Ultimately, the group aims to develop materials and drug delivery platforms that are fundamentally unique yet simple solutions to improve human health.     

Ultrasonic-activated micellar drug delivery for cancer treatment

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

Targeting intracellular targets

Many therapeutic agents have intracellular compartments as their site of action. Targeted delivery of these agents to their specific intracellular targets could result in enhanced therapeutic efficacy and reduced toxicity. Various carriers have been shown useful in targeted delivery of different classes of therapeutic agents. Among these carriers, biodegradable nanoparticles formulated from biocompatible polymers poly(D,L-lactide-co-glycolide) (PLGA) and polylactide (PLA) have shown the potential for sustained intracellular delivery of different therapeutic agents. In this review, we discuss different intracellular targets, barriers to intracellular delivery, mechanism and pathways of intracellular delivery, and various carriers and approaches that have been investigated for intracellular drug delivery.     

Polymeric micelles as nanocarriers for drug delivery

Polymeric micelles are built from amphiphilic polymers through self-assembly effects. Due to their unique core shell structure, small size and modifiable surface, polymeric micelles have been widely investigated as nanoscale drug delivery carriers. Such systems may increase drug solubility and have possible applications in tumour targeting and gene therapy. These biomedical applications require that polymeric micelles are biocompatible, have prolonged blood circulation and possess high drug-loading efficiency. In addition, tumour targeting and smart drug release behaviour need special modification towards micelles with multiplicate functional substances. This review focuses on the present progress of polymeric micelles and highlights some critical issues for their application in drug delivery systems. Composition and micellisation procedures are also briefly discussed.     

Carbon nanomaterials combined with metal nanoparticles for theranostic applications

Among targeted delivery systems, platforms with nanosize dimensions, such as carbon nanomaterials (CNMs) and metal nanoparticles (NPs), have shown great potential in biomedical applications. They have received considerable interest in recent years, especially with respect to their potential utilization in the field of cancer diagnosis and therapy. The many functions of nanomaterials provide opportunities to use them as multimodal agents for theranostics, a combination of therapy and diagnosis. Carbon nanotubes and graphene are some of the most widely used CNMs because of their unique structural and physicochemical properties. Their high specific surface area allows for efficient drug loading and the possibility of functionalization with various bioactive molecules. In addition, CNMs are ideal platforms for the attachment of NPs. In the biomedical field, NPs have also shown tremendous potential for use in drug delivery, non-invasive tumour imaging and early detection due to their optical and magnetic properties. NP/CNM hybrids not only combine the unique properties of the NPs and CNMs but they also exhibit new properties arising from interactions between the two entities. In this review, the preparation of CNMs conjugated to different types of metal NPs and their applications in diagnosis, imaging, therapy and theranostics are presented.     

Molecularly imprinted drug delivery systems

Imprinted polymers are well established as molecular recognition materials but are now being increasingly considered for active biomedical applications such as drug delivery. In this review some highlights of recent research into molecularly imprinted drug delivery and controlled release systems are presented. The key factors controlling recognition and release by imprinted polymer matrices are discussed, the current limiting factors in their properties arising from the synthesis of these materials are considered, and the future prospects for imprinted polymers in drug delivery are outlined.     

Engineered PLGA nanoparticles: an emerging delivery tool in cancer therapeutics

Nanocarriers formulated with the US Food and Drug Administration-approved biocompatible and biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) are being widely explored for the controlled delivery of therapeutic drugs, proteins, peptides, oligonucleotides, and genes. Surface functionalization of PLGA nanoparticles has paved the way to a variety of engineered PLGA-based nanocarriers, which, depending on reticular requirements, can demonstrate a wide variety of combined properties and functions such as prolonged residence time in blood circulation, enhanced oral bioavailability, site-specific drug delivery, and tailored release characteristics. The present review highlights the recent leaps in PLGA-based nanotechnology with a particular focus on cancer therapeutics. Starting with a brief introduction to cancer nanotechnology, we then discuss developmental aspects and the in vitro and in vivo efficacy of PLGA-based nanocarriers in terms of targeted drug or gene delivery. The main objective of this review is to convey information about the state of art and to critically address the limitations and the need for further progress and clinical developments in this emerging technology.