Pectin-based oral drug delivery to the colon

This review presents an overview of studies concerning oral formulations intended for site-specific drug delivery to the colon with pectin as the main excipient. The biological aspects covered include gastrointestinal transit and the enzymatic degradation of pectin. Scintigraphic methods demonstrating the functionality of pectin formulations are discussed. The main focus is on the various formulations reported, including matrix tablets, multiparticulate formulations as pellets and hydrogel beads, and pectin-based coatings. Also included is an evaluation of common excipients employed to improve colon specificity by crosslinking or increasing the hydrophobicity. Finally, properties of the pectin molecules that are important for successful formulations are examined. The conclusion is that the studies found in the literature provide an excellent platform for the development of pectin-based colon delivery systems.     

口服结肠靶向释药系统的制备及应用

目的由于在治疗肠道或某些全身性疾病中具有特殊的优点,口服结肠靶向给药系统受到更多的关注。但消化道的复杂性导致影响药物在结肠靶向释药的因素较多,重现性不好。本文对经口服药物结肠靶向释药的生理因素、目前已有的制备技术及应用进行综述。     

Strategies to improve drug delivery in bladder cancer therapy

Bladder cancer is the ninth most common malignancy in the world featuring very high gender variability in occurrence. Current options for bladder cancer therapy include surgery, immunotherapy, chemotherapy and radiotherapy with a trend towards multimodal treatments. However, successful management remains a challenge for urologists and oncologists because of the high risk for recurrence and progression. Particularly in the field of bladder cancer chemotherapy, efficacy of treatment might be improved by advanced drug delivery strategies aimed at prolonged residence time within the bladder cavity and increased permeability of the bladder wall during intravesical instillation. Moreover, a deeper understanding of the biology of bladder carcinogenesis and malignant progression stimulated the development of a new generation of anticancer drugs for targeted therapies that might result in increased treatment specificity together with lower toxic potential and higher therapeutic indices. This review discusses the available strategies for ‘targeted therapy’, focusing on molecular targets, and for ‘controlled delivery’, comprising all other approaches towards improved drug delivery.     

口服结肠靶向给药系统的研究概况

口服结肠靶向给药系统具有很多优点,尤其对肠病的治疗。本文综述了口服结肠靶向蛤药系统的机制、类型的研究概况。     

线粒体靶向给药系统用于线粒体疾病治疗的研究进展

线粒体是细胞内具有一定结构和功能特性的细胞器,线粒体功能失调将导致机体疾病的发生,它在调节细胞凋亡方面也发挥着重要作用。为了修复线粒体功能的损伤,研究线粒体靶向给药系统显得尤为重要。本文对国内外的研究情况做简要综述。     

Time-controlled oral delivery systems for colon targeting

In recent years, many research efforts have been spent in the achievement of selective delivery of drugs into the colon following oral administration. Indeed, colonic release is regarded as a beneficial approach to the pharmacological treatment or prevention of widespread large bowel pathologies, such as inflammatory bowel disease and adenocarcinoma. In addition, it is extensively explored as a potential means of enhancing the oral bioavailability of peptides, proteins and other biotechnological molecules, which are known to be less prone to enzymatic degradation in the large, rather than in the small, intestine. Based on these premises, several formulation strategies have been attempted in pursuit of colonic release, chiefly including microflora-, pH-, pressure- and time-dependent delivery technologies. In particular, this review is focused on the main design features and release performances of time-controlled devices, which rely on the relative constancy that is observed in the small intestinal transit time of dosage forms.     

Advances in the use of prodrugs for drug delivery to the eye

Introduction: Ocular drug delivery is presented with many challenges, taking into account the distinctive structure of the eye. The prodrug approach has been, and is being, employed to overcome such barriers for some drug molecules, utilizing a chemical modification approach rather than a formulation-based approach. A prodrug strategy involves modification of the active moiety into various derivatives in a fashion that imparts some advantage, such as membrane permeability, site specificity, transporter targeting and improved aqueous solubility, over the parent compound.

Areas covered: The following review is a comprehensive summary of various novel methodologies and strategies reported over the past few years in the area of ocular drug delivery. Some of the strategies discussed involve polymer and lipid conjugation with the drug moiety to impart hydrophilicity or lipophilicity, or to target nutrient transporters by conjugation with transporter-specific moieties and retrometabolic drug design.

Expert opinion: The application of prodrug strategies provides an option for enhancing drug penetration into the ocular tissues, and overall ocular bioavailability, with minimum disruption of the ocular diffusion barriers. Although success of the prodrug strategy is contingent on various factors, such as the chemical structure of the parent molecule, aqueous solubility and solution stability, capacity of targeted transporters and bioreversion characteristics, this approach has been successfully utilized, commercially and therapeutically, in several cases.     

Application of freeze-drying in the development of oral drug delivery systems

ABSTRACT

Introduction: With continual focus on oral drug delivery systems (ODDS), the role of freeze-drying becomes increasingly valuable. While freeze-drying is fundamentally a desiccation process, the advantageous material properties attributed to freeze-drying extend far beyond the preparation of stable pharmaceutical products. The formulation and process variables are important considerations as they affect the final freeze-dried product characteristics. It is of interest to expound on the principles and effects of freeze-drying in the hope of introducing novel products for applications in the development of ODDS.

Areas covered: In this review, basic principles, general formulation and process variables associated with freeze-drying will be covered. The application of freeze-drying in 3 areas: modification of active ingredients, development of novel freeze-dried excipients and development of freeze-dried final dosage forms will be discussed.

Expert opinion: As a pharmaceutical unit operation, freeze-drying has created new dimensions in the area of oral drug delivery, where the properties of the drugs, excipients and characteristics of the final solid dosage form can be modified by the freeze-drying process. With the emergence of new applications, the role of freeze-drying technology in ODDS is indeed a relevant and promising one.     

Targeted cancer drug delivery with aptamer-functionalized polymeric nanoparticles

Abstract

Based on exceptional advantages of aptamers, increasing attention has been presented in the utilise of them as targeted ligands for cancer drug delivery. Recently, the progress of aptamer-targeted nanoparticles has presented new therapeutic systems for several types of cancer with decreased toxicity and improved efficacy. We highlight some of the promising formulations of aptamer-conjugated polymeric nanoparticles for specific targeted drug delivery to cancer cells. This review paper focuses on the current progresses in the use of the novel strategies to aptamer-targeted drug delivery for chemotherapy. An extensive literature review was performed using internet database, mainly PubMed based on MeSH keywords. The searches included full-text publications written in English without any limitation in date. The abstracts, reviews, books as well as studies without obvious relating of aptamers as targeted ligands for cancer drug delivery were excluded from the study. The reviewed literature revealed that aptamers with ability to modify and conjugate to various molecules can be used as targeted cancer therapy agents. However, development of aptamers unique to each individual’s tumour to the development of personalised medicine seems to be needed.     

Recent achievements in colorectal cancer diagnostic and therapy by the use of nanoparticles

Colorectal cancer is a major public health issue, being the third most common cancer in men and the second in women. It is one of the leading causes of cancer deaths. Nanomedicine is an emerging field of interest, many of its aspects being linked to cancer research. Chemotherapy has a well-established role in colorectal cancer management, unfortunately being limited by inability to have a selective distribution, by multidrug resistance and adverse effects. Researches carried out in recent years about nanotechnologies aimed, among others, to resolve the issues mentioned above. Targeted and localized delivery of the chemotherapeutic drugs, using nanoparticles, with selective destruction of cancerous cells would minimize the toxicity on healthy tissues. Also, the use of nanomaterials as contrast agent could improve sensitivity and specificity of diagnosis. The purpose of this review is to highlight the recent achievements of cancer research by use of nanomaterials, in the idea of finding the ideal composite, capable to simultaneous diagnostic and treat cancer.     

Magnetic targeting for site-specific drug delivery: applications and clinical potential

Background: Magnetic vehicles are very attractive for delivery of therapeutic agents as they can be targeted to specific locations in the body through the application of a magnetic field gradient. The magnetic localization of a therapeutic agent results in the concentration of the therapy at the target site consequently reducing or eliminating the systemic drug side effects. Objective: The aim of this review is to provide an update on the progress made in the development of the magnetic targeting technique addressing characteristics of the magnetic carriers and limitations of the current targeting magnet systems. Methods: This review discusses fundamental requirements for the optimal formulation of the magnetic carrier, current applications and potentially new approaches for the magnetically mediated, site-specific localization of therapeutic agents, including drugs, genes and cells. Results/conclusion: More efficient targeting magnetic systems in combination with prolonged circulation lifespan and carriers' surface recognition properties will improve the targeting efficiency of magnetic nanocarriers and enhance therapeutic agent availability at the molecular site of agent action. The main future magnetic targeting applications were categorized emphasizing the most promising directions and possible strategies for improving the magnetic targeting technique.     

Drug delivery systems for the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a severe immune-mediated disease characterized by chronically progressive inflammation and destruction of joints and associated structures. Significant advances in our understanding of its pathophysiology and early diagnosis have led to improved therapy and better outcome. Nevertheless, a number of details in the pathogenesis of RA are still unknown and thus the disease cannot be cured at present. Therefore, current therapy aims at accomplishing complete and long-lasting remission. However, this goal is only achieved in a small proportion of patients, and partial remission and frequent relapses are a common problem. A significant number of patients still do not respond at all to available treatments. In addition, all antirheumatic and immune-modulating drugs developed so far carry a considerable risk of adverse effects, some of which can be severe or even life threatening. This is due, at least in part, to a lack of specificity of most drugs for the target tissue, and to a high volume of distribution for systemic application, which, together with rapid clearance of most drugs, requires frequent application of high dosages. Targeted drug delivery and prolongation of bioavailability would alleviate this issue significantly. This article, therefore, reviews a selection of studies that report promising strategies for joint specific delivery of antiarthritic drugs.     

Polymer-based drug delivery: the quest for local targeting of inflamed intestinal mucosa

Colon-specific drug delivery has found important applications in the wide array of diseases affecting the lower intestinal tract. Recent developments and advancements in the polymer-based colonic delivery ensure targeted therapeutics with reduced systemic adverse effects. Latest progress in the understanding of polymer science has decorated a polymer-based formulation with a number of special features, which may prove effective in the localized drug targeting at specific sites of the intestine. Upon oral administration, polymeric vehicles or polymer-coated formulations serve to protect the drug from premature release and degradation in the upper gastrointestinal tract. Moreover, it also facilitates the selective accumulation and controlled release of the drug at inflamed sites of the colon. This review article focuses on a wide coverage of major polymers, their modifications, pros and cons, mechanism of colon targeting and applications as a vehicle system for colonic drug delivery, with a special emphasis on the inflammatory bowel disease.     

Self-emulsifying drug delivery systems in oral (poly)peptide drug delivery

Introduction: Oral administration of most therapeutic peptides and proteins is mainly restricted due to the enzymatic and absorption membrane barrier of the GI tract. In order to overcome these barriers, various technologies have been explored. Among them, self-emulsifying drug delivery systems (SEDDS) received considerable attention as potential carriers to facilitate oral peptide and protein delivery in recent years.

Areas covered: This review article intends to summarize physiological barriers which limit the bioavailability of orally administrated peptide and protein drugs. Furthermore, the potential of SEDDS to protect incorporated peptides and proteins towards peptidases and proteases and to penetrate the mucus layer is reviewed. Their permeation-enhancing properties and their ability to release the drug in a controlled way are described. Moreover, this review covers the results of in vivo studies providing evidence for this promising approach.

Expert opinion: As SEDDS can: i) provide a protective effect towards a presystemic metabolism; ii) efficiently permeate the intestinal mucus gel layer in order to reach the absorption membrane; and iii) be produced in a very simple and cost-effective manner, they are a promising tool for oral peptide and protein drug delivery.     

Stimuli-responsive nanoscale drug delivery systems for cancer therapy

Abstract

Currently, with the rapid development of nanotechnology, novel drug delivery systems (DDSs) have made rapid progress, in which nanocarriers play an important role in the tumour treatment. In view of the conventional chemotherapeutic drugs with many restrictions such as nonspecific systemic toxicity, short half-life and low concentration in the tumour sites, stimuli-responsive DDSs can deliver anti-tumour drugs targeting to the specific sites of tumours. Owing to precise stimuli response, stimuli-responsive DDSs can control drug release, so as to improve the curative effects, reduce the damage of normal tissues and organs, and decrease the side effects of traditional anticancer drugs. At present, according to the physicochemical properties and structures of nanomaterials, they can be divided into three categories: (1) endogenous stimuli-responsive materials, including pH, enzyme and redox responsive materials; (2) exogenous stimuli-responsive materials, such as temperature, light, ultrasound and magnetic field responsive materials; (3) multi-stimuli responsive materials. This review mainly focuses on the researches and developments of these novel stimuli-responsive DDSs based on above-mentioned nanomaterials and their clinical applications.     

Polysaccharide-based micro/nanocarriers for oral colon-targeted drug delivery

Oral colon-targeted drug delivery has attracted many researchers because of its distinct advantages of increasing the bioavailability of the drug at the target site and reducing the side effects. Polysaccharides that are precisely activated by the physiological environment of the colon hold greater promise for colon targeting. Considerable research efforts have been directed towards developing polysaccharide-based micro/nanocarriers. Types of polysaccharides for colon targeting and in vitro/in vivo assessments of polysaccharide-based carriers for oral colon-targeted drug delivery are summarised. Polysaccharide-based microspheres have gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon (colon cancer, inflammatory bowel disease (IBD), amoebiasis and irritable bowel syndrome (IBS)), but also for it’s potential for the delivery of anti-rheumatoid arthritis and anti-chronic stable angina drugs. Besides, Polysaccharide-based micro/nanocarriers such as microbeads, microcapsules, microparticles, nanoparticles, nanogels and nanospheres are also introduced in this review.     

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.     

甲硝唑微囊口服结肠定位给药系统的制备

目的 :考察甲硝唑微囊口服结肠定位给药系统的制备工艺。方法 :采用液中干燥法制备微囊 ,应用均匀试验设计 ,考察各因素水平对微囊包封率、载药量的影响。按优化后的结果选择实验条件 ,进行重复实验 ,用体外溶出实验考察其结肠定位释放效果。结果 :制备的甲硝唑微囊包封率为 ( 62 .3± 1.3 ) % ,载药量为 ( 5 9.8± 2 .0 ) % ,所制备的片剂在 0 .1mol·L- 1 盐酸溶液和 pH6.8磷酸盐缓冲液中几乎不释放 ,而在 pH7.5磷酸盐缓冲液中 3 0min的平均累积释放量为 82 .13 %。结论 :优化后的制备工艺对甲硝唑微囊口服结肠定位给药系统的研究和应用具有一定的参考价值。     

pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms

Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.