Microsponges: a futuristic approach for oral drug delivery

Introduction: Microparticulate drug delivery systems have, due to their advantages, guided researchers across the globe to explore them as drug carriers. This has, sequentially, led to the development of microsponges in 1988. These porous microspheres were exclusively designed for chronotherapeutic topical drug delivery but attempts to utilize them for oral, pulmonary and parenteral drug delivery were also made. Researchers have extensively studied their properties and characteristics affecting the drug release and loading. Various advances were made with this carrier particle resulting in the development of various novel development techniques and carrier particles.

Areas covered: This review deals with the considerations of the drug material to be entrapped in microsponges, pharmaceutical considerations for fabrication of microsponges, their potential for oral drug delivery, clinical perspectives and also provides an insight on the recent advances made in this field and future prospect.

Expert opinion: Clinical studies show that these carriers can increase drug efficacy. Due to their potential advantages over other carrier particles, microsponges form a prospective platform for the oral delivery of pharmaceuticals and biopharmaceuticals. Although these carriers have several advantages, they too possess some drawbacks which limit their commercialization for oral application.     

Pickering乳液的稳定性及其在药学中的应用研究进展

Pickering乳液是近年来兴起的以固体颗粒作为稳定剂制备而成的一种新型乳液，相比于传统乳液而言，该乳液具有稳定性和生物相容性好，刺激性小，对环境无污染等多种优点。因此，Pickering乳液已成为化妆品、食品、医药、化工等领域中的研究新热点而备受关注。本文在分析Pickering乳液稳定机制及稳定性影响因素的基础上，对近年来Pickering乳液在药学中的应用及药物纳米晶自稳定Pickering乳液的研究进行综述，并根据目前研究中存在的问题对Pickering乳液在未来的发展方向进行了展望，以期为Pickering乳液在药学领域的推广应用提供参考。     

Topical drug delivery using chitosan nano- and microparticles

Introduction: Topical drug delivery offers important benefits for improving the therapeutic effect and reducing systemic side effects of the administered compounds. In addition, utilization of biopolymeric material-based systems can play a key role in developing new topical dosage forms and their applications. This review describes the advances that have been made, new strategies and as well as possible challenges of particular systems of chitosan used in topical drug delivery, including challenging innovations in topical usage of these systems that can make significant impact on clinical practice.

Areas covered: The main area covered is hypothesis that particulate carriers based on chitosan and its derivatives can penetrate the topical barriers from the body. For this reason, the novel studies described emphasize the fact that chitosan-based particular systems are popular that can be tailor-made according to in vitro and in vivo characterization. Such parameters, which are known to influence their in vivo performance, can be modulated by adjusting the formulation conditions of the chitosan-based particular systems for topical application.

Expert opinion: The topical application of drugs with particulate systems comprising a natural polymer, chitosan, is one of the most popular drug delivery routes. The aim of topical use of chitosan particles is to improve the drug bioavailability by prolonging the residence time of drugs applied topically or by enhancing the passing of drugs through the epithelial cells by opening the tight junctions between epithelial cells and also to reduce the side effects of the drugs.     

Compritol 888 ATO: a multifunctional lipid excipient in drug delivery systems and nanopharmaceuticals

Introduction: Compritol® 888 ATO is a lipid excipient that is generally used in cosmetic industry as a surfactant, emulsifying agent and viscosity-inducing agent in emulsions or creams. Based on its chemical composition, Compritol 888 ATO is a blend of different esters of behenic acid with glycerol.

Areas covered: Recently, there has been great interest in the multiple roles that Compritol 888 ATO plays in various pharmaceutical delivery systems. Accordingly, this review aimed at summarizing the current and potential applications of Compritol 888 ATO in various drug delivery areas.

Expert opinion: Different researches have highlighted the feasibility of using Compritol 888 ATO as a lubricant or coating agent for oral solid dosage formulations. It has also been explored as a matrix-forming agent for controlling drug release. At present, the most common pharmaceutical application of Compritol 888 ATO is in lipid-based colloidal drug delivery system such as solid lipid microparticles, solid lipid nanoparticles and nanostructured lipid carriers. Although, Compritol 888 ATO has acceptable regulatory and safety profiles and although the number of articles that emphasize on its applicability as an innovative excipient in pharmaceutical technology is continuously increasing, it is not widely used in the pharmaceutical market products and its use is limited to its sustain release ability in extended release tablets.     

Polymer-drug conjugates: recent progress on administration routes

Introduction: Polymer-drug conjugates are an important part of polymer therapeutics. Recently, they have been used as an appealing platform for drug delivery. As a delivery vector, the route of administration performs a serious impact on the accessibility of drug molecules to their respective target site and therapeutic index. Furthermore, the physicochemical and biological properties of conjugates also correlate distinctly with the route of administration.

Areas covered: This article reviews the recent advances of polymer-drug conjugates as drug delivery systems through parenteral, enteral and topical routes. In particular, it mainly focuses on the classical and emerging routes such as injection, oral, transdermal, pulmonary and ocular routes using polymer-drug conjugates as delivery systems.

Expert opinion: Although polymer-conjugated drug delivery systems reported so far face severe shortcoming of being incomplete methodology and limited routes for administration (mostly concentrated in injection), some polymer carriers like poly(amidoamine) and hyaluronic acid still offer an appealing platform to deliver drug. Acquiring the particular characteristics of each polymer carrier, exploiting novel biodegradable polymer, expanding classical drug administration ways by emerging routes and developing a rational and systematic methodology to design administration routes will be the promising directions.     

Solid lipid microparticles as an approach to drug delivery

Introduction: Solid lipid particles were introduced in the early 1990s as an alternative drug carrier system to emulsions, liposomes and polymeric microparticles. Although lipid nanoparticles have been the object of a substantial number of reviews, fewer are available on lipid microparticles (LMs), despite their distinct advantages, including biocompatibility, ease of production and characterisation, extended release properties and high loading.

Areas covered: This review presents an overview of the advantages and drawbacks of LMs, that is, lipid-based particles with dimensions in the micrometre range. Specific focus is on the role of the main excipients used for LM formulations, lipids and surfactants and their effects on LM properties. An update on preparation techniques and characterisation methods are also presented, with particular emphasis on more recent technologies. The interaction of LMs with biological systems and with cells in particular is reviewed. The various LM administration routes are examined, with special attention to most recent applications (i.e., pulmonary and nasal delivery).

Expert opinion: LMs represent attractive and versatile carrier systems; however, their pharmaceutical applicability has been rather limited. Investigation on the use of LMs for less-established administration routes, such as pulmonary delivery, may provide further interest within the area of LM-based systems, both in industry and in the clinic.     

Topical drug delivery systems: a patent review

Introduction: Topical administration is the favored route for local delivery of therapeutic agents due to its convenience and affordability. The specific challenge of designing a therapeutic system is to achieve an optimal concentration of a certain drug at its site of action for an appropriate duration.

Areas covered: This review summarizes innovations from the past 3 years (2012–2015) in the field of topical drug delivery for the treatment of local infections of the vagina, nose, eye and skin. The review also throws some light on the anatomy and physiology of these organs and their various defensive barriers which affect the delivery of drugs administered topically.

Expert opinion: Topical administration has been gaining attention over the last few years. However, conventional topical drug delivery systems suffer from drawbacks such as poor retention and low bioavailability. The successful formulation of topical delivery products requires the careful manipulation of defensive barriers and selection of a soluble drug carrier. Extensive research is required to develop newer topical drug delivery systems aiming either to improve the efficacy or to reduce side effects compared to current patented systems.     

Liposomes in cosmeceutics

Introduction: Cosmeceuticals are cosmetic products with biologically active ingredients purporting to have medical or drug-like benefits. Some cosmeceuticals can act effectively when reaching their target sites in the deeper layers of the skin. However, the barrier nature of skin causes significant difficulties for compounds to be delivered through. Therefore, scientists are investigating various strategies to overcome these barrier properties. Liposomes have been claimed to improve the topical delivery of compounds.

Areas covered: This paper offers a brief overview of current approaches in the research and development of liposomal formulations to improve the performance of cosmeceuticals, from recent literature. This review deals with the potential of liposomes as a skin delivery system for cosmeceuticals, with a focus on the clinical application of liposomes.

Expert opinion: Liposomes are well-known vesicular cosmetic delivery systems. The topical application of liposomes offers a wide range of advantages including increased moisturization, restoring action, biodegradability, biocompatibility and extended and slow dermal release. Their similar structure to biological membranes allows penetration into the epidermal barrier, compared with other delivery systems. The incorporation of cosmeceuticals using suitable delivery systems is important in the management of cosmetic disorders.     

Topical delivery for the treatment of psoriasis

Importance of the field: Psoriasis is one of the most common human skin diseases. Topical therapy forms the cornerstone in the management of mild-to-moderate psoriasis. Topical therapies are also used as adjunctive to systemic therapy in moderate and severe forms of the disease.

Areas covered in this review: In this review, an overview of psoriasis pathogenesis, new topical medications for psoriasis, new targets and molecules, combination topical therapies and combination of topical and phototherapy is provided. Over the past decade several efficacious and acceptable treatment options have emerged from the age-old therapies. The development of sophisticated formulation options has led to an enhancement in the rate and extent of drug delivery across the skin, increasing therapeutic value and improving patient compliance.

What the reader will gain: Readers will learn about monotherapy and combination topical products as well as new topical drug delivery technology to achieve optimal clinical outcomes. This review will highlight the need to generate more dermal pharmacokinetic data for better understanding of the impact of formulation change on skin pharmacokinetics to help design improved topical drug delivery systems.

Take home message: New topical formulations have the potential to achieve better efficacy with improved safety profile.     

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.     

Characterization of starch Pickering emulsions for potential applications in topical formulations

The aim of this work has been to characterize starch based Pickering emulsions as a first step to evaluate their possible use as vehicles for topical drug delivery. A minor phase study of emulsions with high oil content has been performed. Emulsion stability against coalescence over eight weeks and after mild centrifugation treatment has been studied. The particle size, rheological properties and in vitro skin penetration of emulsions containing three different oils (Miglyol, paraffin and sheanut oil) was investigated. It was shown that it is possible to produce oil in water starched stabilised Pickering emulsions with oil content as high as 56%. Furthermore, this emulsions show good stability during storage over eight weeks and towards mild centrifugation. The particle size of the systems are only dependent on the ratio between oil and starch and for liquid oils the type of oil do not affect the particle size. The type of oil also affects the cosmetic and rheological properties of the creams but did not affect the transdermal diffusion in in vitro tests. However, it seems as if the Pickering emulsions affected the transport over the skin, as the flux was twice that of what has been previously reported for solutions.     

From conventional towards new – natural surfactants in drug delivery systems design: current status and perspectives

Importance of the field: Surfactants play an important role in the development of both conventional and advanced (colloidal) drug delivery systems. There are several commercial surfactants, but a proportionally small group of them is approved as pharmaceutical excipients, recognized in various pharmacopoeias and therefore widely accepted by the pharmaceutical industry.

Areas covered in this review: The review covers some of the main categories of natural, sugar-based surfactants (alkyl polyglucosides and sugar esters) as prospective pharmaceutical excipients. It provides analysis of the physicochemical characteristics of sugar-based surfactants and their possible roles in the design of conventional or advanced drug delivery systems for different routes of administration.

What the reader will gain: Summary and analysis of recent data on functionality, applied concentrations and formulation improvements produced by alkyl polyglucosides and sugar esters in different conventional and advanced delivery systems could be of interest to researchers dealing with drug formulation.

Take home message: Recent FDA certification of an alkyl polyglucoside surfactant for topical formulation presents a significant step in the process of recognition of this relatively new group of surfactants. This could trigger further research into the potential benefits of naturally derived materials in both conventional and new drug delivery systems.     

Pharmaceutical foams: are they the answer to the dilemma of topical nanoparticles?

Nanoparticulate systems have the potential to improve topical drug delivery because of their capacity to enhance drug loading and dissolution, protect chemically unstable therapeutic agents, and improve product aesthetics. However, the commercial use of nanoparticles in topical products is limited because the evidence that they penetrate intact skin is contradictory, and their ability to release active agents in traditional semisolid vehicles is poor. One way to overcome this problem is to formulate nanoparticles in a dynamic delivery system—that is, one that induces a change upon dose actuation so as to promote drug release. Pressurized pharmaceutical foams are one type of dynamic system that can drive a change of state and excipient concentration after dose actuation. This review summarizes the current status of topical products containing nanoparticles, discusses the recent scientific advances in foam production, and investigates the prospect of incorporating nanoparticles into dynamic topical foams. Recent literature suggests that dynamic foams have the potential to break down the nanoparticles loaded within them, improve drug release from nanoparticles, and enhance topical efficacy. Although the published data to support the use of dynamic systems are limited, it is clear that they provide a promising solution to enhance drug release from nanoparticles, and future research work should aim to investigate these systems in more detail.From the Clinical EditorThe use of nanoparticulate systems in topical products is limited as skin penetration and release of active agents remains controversial. Pressurized pharmaceutical foams represent a dynamic system characterized by a change of state and excipient concentration after dose actuation. The review summarizes the current status of topical nanoparticles utilizing this delivery system.     

Advances in use of functionalized carbon nanotubes for drug design and discovery

Introduction: As a part of increasing interest in nanobiotechnology, nanoparticle-based drug discovery as well as development and drug delivery constitute an important area in nanomedicine, and it is also driven by search for new drugs by the pharmaceutical industry. Nanomaterials for pharmaceutical application include carbon nanotubes (CNTs).

Areas covered: This article describes the properties of CNTs, both single-walled CNTs (SWCNTs) and multiwalled CNTs (MWCNTs) with relevance to drug discovery and development. Pharmacokinetics of CNTs as well as CNT-based drug delivery is discussed. The article also looks at how the scope for pharmaceutical applications of CNTs is broadened by conjugation with other molecules and presents the potential therapeutic applications. Finally, the toxicology of CNTs is considered with measures under investigation for reducing it. Literature on CNTs, from the past 5 years, was reviewed and selected publications relevant to drug discovery, development, and delivery were included in the bibliography.

Expert opinion: Carbon nanotubes combine more properties relevant to drug development and delivery than any other nanomaterial. Although a tremendous amount of basic research has been done on CNTs during the past decade, little of this is nearing translation into human applications. No CNT-based medicine has reached clinical trials. Nevertheless, CNT conjugation with other molecules has extended the horizons for their potential therapeutic applications. The most promising of these is PEGylation, which extends the survival of CNTs in circulation. Potential future applications of CNTs include combination of diagnostics and therapeutic drug delivery as well as a component of multimodal therapies for tissue regeneration.     

Lipid nanoparticles as novel delivery systems for cosmetics and dermal pharmaceuticals

INTRODUCTION: Lipid nanoparticles are innovative carrier systems developed as an alternative to traditional vehicles such as emulsions, liposomes and polymeric nanoparticles. Solid lipid nanoparticles (SLN) and the newest nanostructured lipid carriers (NLC) show important advantages for dermal application of cosmetics and pharmaceuticals. AREA COVERED: This article focuses on the main features of lipid nanoparticles, in terms of their preparation and recent advancements. A detailed review of the literature is presented, introducing the importance of these systems in the topical delivery of drugs and active substances. EXPERT OPINION: Lipid nanoparticles are able to enhance drug penetration into the skin, allowing increased targeting to the epidermis and consequently increasing treatment efficiency and reducing the systemic absorption of drugs and cosmetic actives. The complete biodegradation of lipid nanoparticles and their biocompatible chemical nature have secured them the title of 'nanosafe carriers.' SLN and NLC represent a new technological era, which has been taken over by the cosmetic and pharmaceutical industry, which will open new channels for effective topical delivery of substances.     

Nanoparticle-based vaginal drug delivery systems for HIV prevention

Importance of the Field: Several strategies are being investigated for the prevention of heterosexual transmission of HIV. Of these, topical vaginal drug delivery systems, microbicides, are being actively pursued. HIV prevention by means of a topical microbicide has several drug delivery challenges. These challenges include the vaginal mucosal barriers and potential degradation of the drugs in the vaginal lumen due to pH and enzymes present. Also, new drugs being evaluated as microbicides have specific mechanisms of action, which in some cases require drug targeting to a specific site of action. Nanoparticles provide a delivery strategy for targeted or controlled delivery to the vagina which can be applied in the field of HIV prevention.

Areas covered in the review: This review summarizes nanoparticulate systems and their use in mucosal delivery to date. The sexual transmission of HIV along with the various targets to prevent transmission are discussed as well as the potential opportunities, challenges and advantages in using a nanoparticle-based approach for microbicidal drug delivery.

What the reader will gain: This review provides a general understanding of vaginal drug delivery, its challenges, and nanoparticulate delivery systems. Additionally, insight will be gained as to the limited existing application of this technology to the field of HIV prevention.

Take home message: To date, few studies have been published that exploit nanoparticle-based microbicidal delivery to the vagina. The use of nanoparticles for vaginal drug delivery provides an approach to overcome the existing barriers to success.     

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.     

Bile acids and bile acid derivatives: use in drug delivery systems and as therapeutic agents

ABSTRACT

Introduction: Bile acids are biological surfactants and signaling molecules with important paracrine and endocrine functions. The enterohepatic organotropism of bile acids turns these facial amphiphiles into attractive drug delivery systems for selective drug targeting to the liver or to enhance drug bioavailability by improving intestinal absorption and metabolic stability.

Areas covered: Bile acid-based amphiphiles, in the form of mixed micelles, bilosomes, drug conjugates and hybrid lipid-polymer nanoparticles are critically discussed as delivery systems for anticancer drugs, antimicrobial agents and therapeutic peptides/proteins, including vaccines. Therapeutic applications of bile acid derivatives as cytotoxic and neuroprotective agents are also addressed.

Expert opinion: Bile acids play an important role in modulating cancer therapy and novel derivatives with cytotoxic activity not restricted to the gastrointestinal tract can be expected. Selective toxicity targeting the bacterial membrane remains an attractive area of research for further development of bile acid-based bactericidal agents. On the other hand, the neuroprotective properties of some bile acids offer therapeutic potential in neurodegenerative disorders. Bile acid-based nanoparticles are also a growing research area due to the unique characteristics and tunable properties of these nanosystems. Therefore, multifaceted pharmaceutical and biomedical applications of bile salts are to be expected in the near future.     

Oral delivery of peptides and proteins using lipid-based drug delivery systems

Introduction: In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism by which intestinal absorption of peptides and proteins is promoted.

Areas covered: The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two most important barriers (extensive enzymatic degradation and poor transmucosal permeability). This paper also gives a clear-cut idea about advantages and drawbacks of using different lipidic colloidal carriers ((micro)emulsions, solid lipid core particles and liposomes) for oral delivery of peptides and proteins.

Expert opinion: Lipid-based DDS are safe and suitable for oral delivery of peptides and proteins. Significant progress has been made in this area with several technologies on clinical trials. However, a better understanding of the mechanism of action in vivo is needed in order to improve the design and development of lipid-based DDS with the desired bioavailability and therapeutic profile.