Drug delivery by red blood cells: vascular carriers designed by mother nature

Importance of the field: Vascular delivery of several classes of therapeutic agents may benefit from carriage by red blood cells (RBC), for example, drugs that require delivery into phagocytic cells and those that must act within the vascular lumen. The fact that several protocols of infusion of RBC-encapsulated drugs are now being explored in patients illustrates a high biomedical importance for the field.

Areas covered by this review: Two strategies for RBC drug delivery are discussed: encapsulation into isolated RBC ex vivo followed by infusion in compatible recipients and coupling therapeutics to the surface of RBC. Studies of pharmacokinetics and effects in animal models and in human studies of diverse therapeutic enzymes, antibiotics and other drugs encapsulated in RBC are described and critically analyzed. Coupling to RBC surface of compounds regulating immune response and complement, affinity ligands, polyethylene glycol alleviating immune response to donor RBC and fibrinolytic plasminogen activators are described. Also described is a new, translation-prone approach for RBC drug delivery by injection of therapeutics conjugated with fragments of antibodies providing safe anchoring of cargoes to circulating RBC, without need for ex vivo modification and infusion of RBC.

What the reader will gain: Readers will gain historical perspective, current status, challenges and perspectives of medical applications of RBC for drug delivery.

Take home message: RBC represent naturally designed carriers for intravascular drug delivery, characterized by unique longevity in the bloodstream, biocompatibility and safe physiological mechanisms for metabolism. New approaches for encapsulating drugs into RBC and coupling to RBC surface provide promising avenues for safe and widely useful improvement of drug delivery in the vascular system.     

Biomedical applications of microneedles in therapeutics: recent advancements and implications in drug delivery

Introduction: The skin, as the largest organ, is a better option for drug delivery in many diseases. However, most transdermal delivery is difficult due to the low permeability of therapeutics across the various skin layers. There have been many innovations in transdermal drug delivery to enhance the therapeutic efficacy of the drugs administered. Microneedles (MN), micron sized needles, are of great interest to scientists as a new therapeutic vehicle through transdermal routes, especially for vaccines, drugs, small molecules, etc.

Areas covered: This review covers new insights into different types of MNs such as solid, hollow, coated and dissolving MNs (SMNs, HMNs, CMNs, and DMNs) for selected biomedical applications in detail. Specific focus has been given to CMNs and DMNs for vaccine and drug delivery applications with recent developments in new MNs covered.

Expert opinion: This review explores the feasibility of innovative MNs used as a drug delivery carrier. Because most of the SMNs and HMNs have many limitations, it is difficult to achieve therapeutic efficacy. Therefore, many scientists are investigating functional modifications of MNs through covalent and non-covalent methods, especially for CMNs and DMNs. The biomedical applications of MNs are growing and new exciting improvements could be achieved, thus resulting in better micro/nano technologies in the near future.     

Cell-mediated drug delivery

Introduction: Drug targeting to sites of tissue injury, tumor or infection with limited toxicity is the goal for successful pharmaceutics. Immunocytes (including mononuclear phagocytes (dendritic cells, monocytes and macrophages), neutrophils and lymphocytes) are highly mobile; they can migrate across impermeable barriers and release their drug cargo at sites of infection or tissue injury. Thus, immune cells can be exploited as Trojan horses for drug delivery.

Areas covered: This paper reviews how immunocytes laden with drugs can cross the blood–brain or blood–tumor barriers to facilitate treatments for infectious diseases, injury, cancer, or inflammatory diseases. The promises and perils of cell-mediated drug delivery are reviewed, with examples of how immunocytes can be harnessed to improve therapeutic end points.

Expert opinion: Using cells as delivery vehicles enables targeted drug transport and prolonged circulation times, along with reductions in cell and tissue toxicities. Such systems for drug carriage and targeted release represent a new disease-combating strategy being applied to a spectrum of human disorders. The design of nanocarriers for cell-mediated drug delivery may differ from those used for conventional drug delivery systems; nevertheless, engaging different defense mechanisms in drug delivery may open new perspectives for the active delivery of drugs.     

Drug delivery technologies for autoimmune disease

Importance of the field: Targeting autoimmune disease poses two main challenges. The first is to identify unique targets to suppress directly or indirectly autoreactive cells exclusively. The second is to penetrate target tissues to deliver specifically drugs to desired cells that can achieve a therapeutic outcome.

Areas covered in this review: Herein, the range of drug delivery methods available and under development and how they can be useful to treat autoimmune diseases are discussed. Polymer delivery methods, as well as biological methods that include fusion proteins, targeted antibodies, recombinant viruses and cell products are compared.

What the reader will gain: Readers will gain insight into the progression of clinical trials for different technologies and drug delivery methods useful for targeting and modulating the function of autoreactive immune cells.

Take home message: Several tissue-specific polymer-based and biologic drug delivery systems are now in Phase II/III clinical trials. Although these trials are focused mainly on cancer treatment, lessons from these trials can guide the use of the same agents for autoimmunity therapeutics.     

Biodegradable polymers: an update on drug delivery in bone and cartilage diseases

ABSTRACT

Introduction: The unique structure of bone and cartilage makes the systemic delivery of free drugs to those connective tissues very challenging. Consequently, effective and targeted delivery for bone and cartilage is of utmost importance. Engineered biodegradable polymers enable designing carriers for a targeted and temporal controlled release of one or more drugs in concentrations within the therapeutic range. Also, tissue engineering strategies can allow drug delivery to advantageously promote the in situ tissue repair.

Areas covered: This review article highlights various drug delivery systems (DDS) based on biodegradable biomaterials to treat bone and/or cartilage diseases. We will review their applications in osteoporosis, inflammatory arthritis (namely osteoarthritis and rheumatoid arthritis), cancer and bone and cartilage tissue engineering.

Expert opinion: The increased knowledge about biomaterials science and of the pathophysiology of diseases, biomarkers, and targets as well as the development of innovative tools has led to the design of high value-added DDS. However, some challenges persist and are mainly related to an appropriate residence time and a controlled and sustained release over a prolonged period of time of the therapeutic agents. Additionally, the poor prediction value of some preclinical animal models hinders the translation of many formulations into the clinical practice.     

The progressive role of acoustic cavitation for non-invasive therapies,contrast imaging and blood-tumor permeability enhancement

ABSTRACT

Introduction: Drug delivery pertaining to acoustic cavitation generated from ultrasonic (US) irradiation is advantageous for devising smarter and more advanced therapeutics. The aim is to showcase microbubbles as drug carriers and robust theranostic for non-invasive therapies across diverse biomedical disciplines, highlighting recent technologies in this field for overcoming the blood-brain barrier (BBB) to treat cancers and neurological disorders.

Areas covered: This article reviews work on the optimized tuning of ultrasonic parameters, sonoporation, transdermal and responsive drug delivery, acoustic cavitation in vasculature and oncology, contrast imaging for real-time magnification of cell-microbubble dynamics and biomolecular targeting. Scholarly literature was sought through database search on key terminology, latest topics, reputable experts and established journals over the last five years.

Expert opinion: Cavitation offers immense promise in overcoming current diffusion and convection limitations for treating skull/brain/vascular/tissue injuries and ablating tumors to minimize chronic/acute effects. Since stable cavitation facilitates the restoration of US-opened BBB and the modulation of drug concentration, US equipment with programmable imaging modality and sensitivity are envisaged to create safer miniaturized devices for personalized care. Due to differing biomedical protocols with regard to specific medical conditions, quantitative and qualitative controls are mandatory before translation to real-life clinical applications can be accomplished.     

Therapeutic applications of hydrogels in oral drug delivery

Introduction: Oral delivery of therapeutics, particularly protein-based pharmaceutics, is of great interest for safe and controlled drug delivery for patients. Hydrogels offer excellent potential as oral therapeutic systems due to inherent biocompatibility, diversity of both natural and synthetic material options and tunable properties. In particular, stimuli-responsive hydrogels exploit physiological changes along the intestinal tract to achieve site-specific, controlled release of protein, peptide and chemotherapeutic molecules for both local and systemic treatment applications.

Areas covered: This review provides a wide perspective on the therapeutic use of hydrogels in oral delivery systems. General features and advantages of hydrogels are addressed, with more considerable focus on stimuli-responsive systems that respond to pH or enzymatic changes in the gastrointestinal environment to achieve controlled drug release. Specific examples of therapeutics are given. Last, in vitro and in vivo methods to evaluate hydrogel performance are discussed.

Expert opinion: Hydrogels are excellent candidates for oral drug delivery, due to the number of adaptable parameters that enable controlled delivery of diverse therapeutic molecules. However, further work is required to more accurately simulate physiological conditions and enhance performance, which is important to achieve improved bioavailability and increase commercial interest.     

Advances in lipid-based drug delivery: enhancing efficiency for hydrophobic drugs

Introduction: Many drug candidates with high therapeutic efficacy have low water solubility, which limits the administration and transport across physiological barriers, for example, the tumor tissue barrier. Therefore, strategies are needed to permeabilize the physiological barriers safely so that hydrophobic drugs may be delivered efficiently.

Areas covered: This review focuses on prospects for therapeutic application of lipid-based drug delivery carriers that increase hydrophobic drugs to improve their solubility, bioavailability, drug release, targeting and absorption. Moreover, novel techniques to prepare for lipid-based drug delivery to extend pharmaceuticals with poor bioavailability such as surface modifications of lipid-based drug delivery are presented. Industrial developments of several drug candidates employing these strategies are discussed, as well as applications and clinical trials.

Expert opinion: Overall, hydrophobic drugs can be encapsulated in the lipid-based drug delivery systems, represent a relatively safe and promising strategy to extend drug retention, lengthen the lifetime in the circulation, and allow active targeting to specific tissues and controllable drug release in the desirable sites. However, there are still noticeable gaps that need to be filled before the theoretical advantage of these formulations may truly be realized such as investigation on the use of lipid-based drug delivery for administration routes. This research may provide further interest within the area of lipid-based systems, both in industry and in the clinic.     

Stents as a platform for drug delivery

Introduction: Drug delivery stents have proved their efficacy at preventing coronary restenosis and their potential in treating the occlusion or stricture of other body passageways, such as peripheral vessels and alimentary canals. The drug delivery systems on such stent platforms contribute to this improved therapeutic efficacy by providing improved drug delivery performance, along with reduced concerns encountered by current stents (e.g., in-stent restenosis, late thrombosis and delayed healing).

Areas covered: A wide variety of drug delivery stents (metallic drug-eluting stents, absorbable drug-eluting stents, and polymer-free drug-eluting stents for coronary and other applications) that are commercially available or under investigation are collected and summarized in this review, with emphasis on their drug delivery aspects. This review also gives insights into the progression of stent-based drug delivery strategies for the prevention of stent-related problems, or the treatment of local diseases. In addition, a critical analysis of the advantages and challenges of such strategies is provided.

Expert opinion: With an in-depth understanding of drug properties, tissue/organ biology and disease conditions, stent drug delivery systems can be improved further, to endow the stents with better efficacy and safety, along with lower toxicity. There is also a great need for stents that can simultaneously deliver multiple drugs, to treat complex diseases from multiple aspects, or to treat several diseases at the same time. Drug release kinetics greatly determines the stent performance, thus effective strategies should also be developed to achieve customized kinetics.     

Oral colon-specific therapeutic approaches toward treatment of inflammatory bowel disease

Introduction: Inflammatory bowel disease (IBD) is a chronic relapsing idiopathic disease. In clinical terms, most patients require lifelong medication associated with possible unpleasant adverse effects. Oral colon-specific drug delivery systems are designed to deliver therapeutic drugs to the inflamed colon to target pathophysiological manifestations of IBD. The aim is to maintain the drug with proper concentration in the inflamed colon, to enhance drug residence time and to minimize drug absorption by healthy tissues.

Areas covered: This review addresses the main barriers for colon-specific drug delivery from organism, tissue and cell levels, respectively. It also summarizes novel colon-specific therapeutic strategies using microparticles and nanoparticles.

Expert opinion: Oral colon-specific drug delivery represents a possible approach toward efficient treatment of IBD. As the environment of the gastrointestinal tract is harsh and intricate, this approach requires that drug carriers can respond to specific environmental factors of the inflamed colon, permitting stimulus-responsive release of loaded drugs to specific cells or even into specific organelles within cells.     

Recent advances in the role of supramolecular hydrogels in drug delivery

Introduction: Supramolecular hydrogels, formed by noncovalent crosslinking of polymeric chains in water, constitute an interesting class of materials that can be developed specifically for drug delivery and biomedical applications. The biocompatibility, stimuli responsiveness to various external factors, and powerful functionalization capacity of these polymeric networks make them attractive candidates for novel advanced dosage form design.

Areas covered: This review summarizes the significance of supramolecular hydrogels in various biomedical and drug delivery applications. The recent advancement of these hydrogels as potential advanced drug delivery systems (for gene, protein, anticancer and other drugs) is discussed. The importance of these hydrogels in biomedical applications, particularly in tissue engineering, biosensing, cell-culture research and wound treatment is briefly described.

Expert opinion: The use of supramolecular hydrogels in drug delivery is still in very early stages. However, the potential of such a system is undeniably important and very promising. A number of recent studies have been conducted, which mainly focus on the use of cyclodextrin-based host–guest complex as well as other supramolecular motifs to form supramolecular hydrogels for delivery of various classes of drugs, therapeutic agents, proteins and genes. However, there are still plenty of opportunities for further development in this area for drug delivery and other biomedical applications.     

Extended release formulations using silk proteins for controlled delivery of therapeutics

ABSTRACT

Introduction: Silk is a promising biomaterial for controlled delivery of therapeutics and has a unique protein chemistry that can be tuned to form different carrier formats. The protein has been studied for sustained release depot systems for the targeted or localized delivery of drugs.

Areas covered: An overview of natural silk proteins for controlled delivery of therapeutics is provided, with a focus on the features of silk proteins that allow them to be useful tools for controlled delivery. Recent applications of natural silk proteins as controlled delivery systems are also summarized.

Expert opinion: The versatility of silk proteins makes them desirable biomaterials for a broad range of applications for controlled delivery of both small and large molecules. Further, the degradation profile leading to peptides and amino acids provides compatibility with pH-sensitive therapeutics. While silk sericin and spider silks are under study, silk fibroin extracted from silkworms (e.g. Bombyx mori) dominates pharmaceutical studies with silk. Silk fibroin can be formed into drug delivery tools for systemic or local injections, topical and transdermal applications, and implantation; depending on the target disease and therapeutic molecule. In vitro to in vivo correlations and scale-up needs are the next steps towards clinical applications.     

Drug delivery across the blood–brain barrier using focused ultrasound

Introduction: The presence of the blood–brain barrier (BBB) is a significant impediment to the delivery of therapeutic agents to the brain for treatment of brain diseases. Focused ultrasound (FUS) has been developed as a noninvasive method for transiently increasing the permeability of the BBB to promote drug delivery to targeted regions of the brain.

Areas covered: The present review briefly compares the methods used to promote drug delivery to the brain and describes the benefits and limitations of FUS technology. We summarize the experimental data which shows that FUS, combined with intravascular microbubbles, increases therapeutic agent delivery into the brain leading to significant reductions in pathology in preclinical models of disease. The potential for translation of this technology to the clinic is also discussed.

Expert opinion: The introduction of magnetic resonance imaging guidance and intravascular administration of microbubbles to FUS treatments permits the consistent, transient and targeted opening of the BBB. The development of feedback systems and real-time monitoring techniques improve the safety of BBB opening. Successful clinical translation of FUS has the potential to revolutionize the treatment of brain disease resulting in effective, less-invasive treatments without the need for expensive drug development.     

Sonopermeation to improve drug delivery to tumors: from fundamental understanding to clinical translation

ABSTRACT

Introduction: Ultrasound in combination with microbubbles can make cells and tissues more accessible for drugs, thereby achieving improved therapeutic outcomes. In this review, we introduce the term ‘sonopermeation’, covering mechanisms such as pore formation (traditional sonoporation), as well as the opening of intercellular junctions, stimulated endocytosis/transcytosis, improved blood vessel perfusion and changes in the (tumor) microenvironment. Sonopermeation has gained a lot of interest in recent years, especially for delivering drugs through the otherwise impermeable blood-brain barrier, but also to tumors.

Areas covered: In this review, we summarize various in vitro assays and in vivo setups that have been employed to unravel the fundamental mechanisms involved in ultrasound-enhanced drug delivery, as well as clinical trials that are ongoing in patients with brain, pancreatic, liver and breast cancer. We summarize the basic principles of sonopermeation, describe recent findings obtained in (pre-) clinical trials, and discuss future directions.

Expert Opinion: We suggest that an improved mechanistic understanding, and microbubbles and ultrasound equipment specialized for drug delivery (and not for imaging) are key aspects to create more effective treatment regimens by sonopermeation. Real-time feedback and tools to predict therapeutic outcome and which tumors/patients will benefit from sonopermeation-based interventions will be important to promote clinical translation.     

Towards a targeted multi-drug delivery approach to improve therapeutic efficacy in breast cancer

Importance of the field: Significant improvements in breast cancer treatments have resulted in a significant decrease in mortality. However, current breast cancer therapies, for example, chemotherapy, often result in high toxicity and nonspecific side effects. Other treatments, such as hormonal and antiangiogenic therapies, often have low treatment efficacy if used alone. In addition, acquired drug resistance decreases further the treatment efficacy of these therapies. Intra-tumor heterogeneity of the tumor tissue may be a major reason for the low treatment efficacy and the development of chemoresistance. Therefore, targeted multi-drug therapy is a valuable option for addressing the multiple mechanisms that may be responsible for reduced efficacy of current therapies.

Areas covered in this review: In this article, different classes of drugs for treating breast cancer, the possible reasons for the drug resistance in breast cancer, as well as different targeted drug delivery systems are summarized. The current targeting strategies used in cancer treatment are discussed.

What the reader will gain: This article considers the current state of breast cancer therapy and the possible future directions in targeted multi-drug delivery for treating breast cancer.

Take home message: A better understanding of tumor biology and physiological responses to nanoparticles, as well as advanced nanoparticle design, are needed to improve the therapeutic outcomes for treating breast cancer using nanoparticle-based targeted drug delivery systems. Moreover, selective delivery of multi-drugs to tumor tissue using targeted drug delivery systems may reduce systemic toxicity further, overcome drug resistances, and improve therapeutic efficacy in treating breast cancer.     

Hyaluronan-based delivery of therapeutic oligonucleotides for treatment of human diseases

Introduction: Oligonucleotide therapeutics such as antisense oligonucleotides and siRNA requires chemical modifications and nano-sized carriers to circumvent stability problems in vivo, to reach target tissues, and to overcome tissue and cellular barriers. Hyaluronic acid (HA), already utilized in drug delivery and tissue engineering, possess properties that are useful to solve these problems and achieve full potential of oligonucleotide therapeutics.

Areas covered: Complexes of oligonucleotide therapeutics with HA are discussed in terms of interactions providing the complexes formation and genes targeted by the therapeutics to cure diseases such as cancer, atherosclerosis, liver cirrhosis, and inflammation. The achieved therapeutic effects are rationalized as consequences of biodistribution, cell internalization and endosomal escape provided by HA.

Expert opinion: Design of electrostatic, coordination, and hydrophobic interactions as well as covalent conjugation between oligonucleotide drugs, HA macromolecules and intermediate ligands are crucial for carrier–cargo association and dissociation under different conditions to impart oligonucleotides stability in vivo, their accumulation in diseased organs, cellular uptake, and dissociation in cytoplasm intact. These are the delivery factors that provides eventual complex formation of oligonucleotide therapeutics with their mRNA, microRNA, or protein targets. Elucidation of the impact of structural parameters of oligonucleotide/HA complexes on their therapeutic effect in vivo is important for the future rational design of the delivery agents.     

Composite polymer-bioceramic scaffolds with drug delivery capability for bone tissue engineering

Introduction: Next-generation scaffolds for bone tissue engineering (BTE) should exhibit the appropriate combination of mechanical support and morphological guidance for cell proliferation and attachment while at the same time serving as matrices for sustained delivery of therapeutic drugs and/or biomolecular signals, such as growth factors. Drug delivery from BTE scaffolds to induce the formation of functional tissues, which may need to vary temporally and spatially, represents a versatile approach to manipulating the local environment for directing cell function and/or to treat common bone diseases or local infection. In addition, drug delivery from BTE is proposed to either increase the expression of tissue inductive factors or to block the expression of others factors that could inhibit bone tissue formation. Composite scaffolds which combine biopolymers and bioactive ceramics in mechanically competent 3D structures, including also organic–inorganic hybrids, are being widely developed for BTE, where the affinity and interaction between biomaterials and therapeutic drugs or biomolecular signals play a decisive role in controlling the release rate.

Areas covered: This review covers current developments and applications of 3D composite scaffolds for BTE which exhibit the added capability of controlled delivery of therapeutic drugs or growth factors. A summary of drugs and biomolecules incorporated in composite scaffolds and approaches developed to combine biopolymers and bioceramics in composites for drug delivery systems for BTE is presented. Special attention is given to identify the main challenges and unmet needs of current designs and technologies for developing such multifunctional 3D composite scaffolds for BTE.

Expert opinion: One of the major challenges for developing composite scaffolds for BTE is the incorporation of a drug delivery function of sufficient complexity to be able to induce the release patterns that may be necessary for effective osseointegration, vascularization and bone regeneration. Loading 3D scaffolds with different biomolecular agents should produce a codelivery system with different, predetermined release profiles. It is also envisaged that the number of relevant bioactive agents that can be loaded onto scaffolds will be increased, whilst the composite scaffold design should exploit synergistically the different degradation profiles of the organic and inorganic components.     

Albumin and its application in drug delivery

Introduction: Rapid clearance of drugs from the body results in short therapeutic half-life and is an integral property of many protein and peptide-based drugs. To maintain the desired therapeutic effect patients are required to administer higher doses more frequently, which is inconvenient and risks undesirable side effects. Drug delivery technologies aim to minimise the number of administrations and dose-related toxicity while maximising therapeutic efficacy.

Areas covered: This review describes albumin’s inherent biochemical and biophysical properties, which make it an attractive drug delivery platform and the developmental status of drugs that are associated, conjugated or genetically fused with albumin. Albumin interacts with a number of cell surface receptors including gp18, gp30, gp60, FcRn, cubilin and megalin. The importance of albumin’s interaction with the FcRn receptor, the basis for albumin’s long circulatory half-life, is described, as are engineered albumins with improved pharmacokinetics. Albumin naturally accumulates at tumours and sites of inflammation, a characteristic which can be augmented by the addition of targeting ligands. The development of albumin drug conjugates which reply upon this property is described.

Expert opinion: Albumin’s inherent biochemical and biophysical properties make it an ideal drug delivery platform. Recent advances in our understanding of albumin physiology and the improvement in albumin-based therapies strongly suggest that albumin-based therapies have a significant advantage over alternative technologies in terms of half-life, stability, versatility, safety and ease of manufacture. Given the importance of the albumin:FcRn interaction, the interpretation of the pharmacokinetic and pharmacodynamic profiles of albumin-based therapeutics with disturbed albumin:FcRn interaction may have to be reassessed. The FcRn receptor has additional functionality, especially in relation to immunology, antigen presentation and delivery of proteins across mucosal membranes, consequently albumin-based fusions and conjugates may have a future role in oral and pulmonary-based vaccines and drug delivery.     

Low-frequency sonophoresis: application to the transdermal delivery of macromolecules and hydrophilic drugs

Importance of the field: Transdermal delivery of macromolecules provides an attractive alternative route of drug administration when compared to oral delivery and hypodermic injection because of its ability to bypass the harsh gastrointestinal tract and deliver therapeutics non-invasively. However, the barrier properties of the skin only allow small, hydrophobic permeants to traverse the skin passively, greatly limiting the number of molecules that can be delivered via this route. The use of low-frequency ultrasound for the transdermal delivery of drugs, referred to as low-frequency sonophoresis (LFS), has been shown to increase skin permeability to a wide range of therapeutic compounds, including both hydrophilic molecules and macromolecules. Recent research has demonstrated the feasibility of delivering proteins, hormones, vaccines, liposomes and other nanoparticles through LFS-treated skin. In vivo studies have also established that LFS can act as a physical immunization adjuvant. LFS technology is already clinically available for use with topical anesthetics, with other technologies currently under investigation.

Areas covered in this review: This review provides an overview of mechanisms associated with LFS-mediated transdermal delivery, followed by an in-depth discussion of the current applications of LFS technology for the delivery of hydrophilic drugs and macromolecules, including its use in clinical applications.

What the reader will gain: The reader will gain an insight into the field of LFS-mediated transdermal drug delivery, including how the use of this technology can improve on more traditional drug delivery methods.

Take home message: Ultrasound technology has the potential to impact many more transdermal delivery platforms in the future due to its unique ability to enhance skin permeability in a controlled manner.     

Microemulsions as drug delivery systems to improve the solubility and the bioavailability of poorly water-soluble drugs

Importance of the field: Microemulsions have been studied extensively as potential drug delivery vehicles for poorly water-soluble drugs. An understanding of the physicochemical and biopharmaceutical characteristics of the microemulsions according to administration routes will provide guidance for designing the formulations of microemulsions.

Areas covered in this review: In this paper, the use and the characteristics of microemulsions as drug delivery vehicles are reviewed. As the formulations of the microemulsion always include a great amount of surfactant and co-surfactant, which may cause hemolysis or histopathological alterations of the tissue, the potential toxicity or the irritancy of microemulsions is also discussed in this paper.

What the reader will gain: Developments of microemulsions for poorly water-soluble drugs in recent years are included in this review. Several factors limiting the commercial or clinical use of microemulsions are also discussed.

Take home message: Considering the potential in enhanced drug uptake/permeation and facing the limitations, their unique properties make microemulsions a promising vehicle for poorly water-soluble drugs.