Transfollicular Drug Delivery

The hair follicle, hair shaft, and sebaceous gland collectively form what is recognized as the pilosebaceous unit. This complex, three-dimensional structure within the skin possesses a unique biochemistry, metabolism and immunology. Recent studies have focused on the hair follicle as a potential pathway for both localized and systemic drug delivery. Greater understanding of the structure and function of the hair follicle may facilitate rational design of drug formulations to target follicular delivery. Targeted drug delivery may enhance current therapeutic approaches to treating diseases of follicular origin. Presented here is a review of follicular drug delivery and a discussion of the feasibility of the pilosebaceous unit as a target site.     

Evaluation of an Enzyme-Containing Capsular Shaped Pulsatile Drug Delivery System

Purpose. To develop an enzymatically-controlled pulsatile drug release system based on an impermeable capsule body, which contains the drug and is closed by an erodible pectin/pectinase-plug. Methods. The plug was prepared by direct compression of pectin and pectinase in different ratios. In addition to the disintegration times of the plugs, the lag times and the release profiles of the pulsatile system were determined as a function of pectin:enzyme ratio, the pH of the surrounding medium, and the addition of buffering or chelating agents. Results. The disintegration time of the plug, respectively the lag time prior to the drug release was controlled by the pectin:enzyme ratio and the plug weight. The inclusion of a buffering agent within the plug lead to a plug disintegration independent of the surrounding pH. The addition of Na-EDTA hindered the formation of non-soluble calcium pectinate in the presence of calcium ions in the environment. The addition of effervescent agents to the capsule content resulted in a rapid emptying of the capsule content after plug degradation. Conclusions. A pulsatile drug delivery system based on an erodible pectin plug containing a pectinolytic enzyme was developed. The drug release was controlled by the enzymatic degradation and dissolution of pectin.     

The role of hair follicles in the percutaneous absorption of caffeine

Aims

The skin and its appendages are our protective shield against the environment and are necessary for the maintenance of homeostasis. Hypotheses concerning the penetration of substances into the skin have assumed diffusion through the lipid domains of the stratum corneum. It is believed that while hair follicles represent a weakness in the shield, they play a subordinate role in the percutaneous penetration processes. Previous investigation of follicular penetration has mostly addressed methodical and technical problems. Our study utilized a selective closure technique of hair follicle orifices in vivo, for the comparison of interfollicular and follicular absorption rates of caffeine in humans.

Methods

Every single hair follicle within a delimited area of skin was blocked with a microdrop of a special varnish-wax-mixture in vivo. Caffeine in solution was topically applied and transcutaneous absorption into the blood was measured by a new surface ionization mass spectrometry (SI/MS) technique, which enabled a clear distinction to be made between interfollicular and follicular penetration of a topically applied substance.

Results

Caffeine (3.75 ng ml⁻¹) was detected in blood samples, 5 min after topical application, when the follicles remained open. When the follicles were blocked, caffeine was detectable after 20 min (2.45 ng ml⁻¹). Highest values (11.75 ng caffeine ml⁻¹) were found 1 h after application when the follicles were open.

Conclusions

Our findings demonstrate that hair follicles are considerable weak spots in our protective sheath against certain hydrophilic drugs and may allow a fast delivery of topically applied substances.

What is already known about this subject

• In recent years, it has been suggested that hair follicles represent important shunt routes into the skin for drugs and chemicals [1–3].
• In vitro studies have shown the importance of skin appendages for skin penetration by hydrophilic compounds [4]. Investigation of follicular penetration in vivo has been difficult due to the absence of appropriate analytical methods or suitable animal model systems.
• Recently, a new method was described that quantifies follicular penetration in vivo by using selective closure of hair follicles [5].
• Caffeine is frequently used in skin penetration experiments as a model for highly water-soluble compounds. Occlusion [6] and skin thickness [7] seem to have little influence on the penetration of caffeine. However, percutaneous absorption rates for caffeine exhibit regional skin differences in humans in vivo[1].

What this study adds

• The results of the present study demonstrate that a fast drug delivery of caffeine occurs through shunt routes. Therefore, hair follicles are considerable weak spots in our protective sheath against penetration into the body by hydrophilic substances.
• We showed that there is a quantitative distinction between follicular penetration and interfollicular diffusion of caffeine in vivo.
• These findings are of importance for the development and optimization of topically applied drugs and cosmetics. In addition, such properties must be considered in the development of skin protection measures.

     

Recent developments in novel drug delivery systems for wound healing

Introduction: Complete regeneration and restoration of the skin’s structure and function with no or minimal scarring remains the goal of wound healing research. Novel pharmaceutical carriers have the potential to deliver wound healing drugs such as antibiotics, antimicrobials, human EGFs, and so on. Thus, offering a potential platform to overcome the limitations of conventional wound dressings.

Areas covered: This review will describe various techniques such as microspheres, nanoparticles, liposomes, solid lipid nanoparticles, nano and microemulsions, sponges and wafers, and so on, that are successfully applied as carriers for wound healing drugs. Results of various studies including in vitro and in vivo experiments are also discussed.

Expert opinion: Controlled and localized delivery of wound healing drugs to the wounds is more convenient than systemic administration as higher concentrations of the medication are delivered directly to the desired area in a sustained manner. They are also capable of providing optimum environmental conditions to facilitate wound healing while eliminating the need for frequent changes of dressings. As the number of people suffering from chronic wounds is increasing around the world, controlled delivery of wound healing agents have enormous potential for patient-friendly wound management.     

Gastroretentive microparticles for drug delivery applications

Many strategies have been proposed to explore the possibility of exploiting gastroretention for drug delivery. Such systems would be useful for local delivery, for drugs that are poorly soluble at higher pH or primarily absorbed from the proximal small intestine. Generally, the requirements of such strategies are that the vehicle maintains controlled drug release and exhibits prolonged residence time in the stomach. Despite widespread reporting of technologies, many have an inherent drawback of variability in transit times. Microparticulate systems, capable of distributing widely through the gastrointestinal tract, can potentially minimise this variation. While being retained in the stomach, the drug content is released slowly at a desired rate, resulting in reduced fluctuations in drug levels. This review summarises the promising role of microencapsulation in this field, exploring both floating and mucoadhesive microparticles and their application in the treatment of Helicobacter pylori, highlighting the clinical potential of eradication of this widespread infection.     

多糖及其衍生物在药物传递系统中的应用研究新进展

多糖是一类生物相容性好、无毒、非免疫原性的生物材料,现已广泛应用于药物传递系统。综述海藻酸盐、几丁质、葡聚糖、透明质酸和肝素等多糖及其衍生物的理化和生物学特性以及在药物传递系统中的应用进展。     

口服结肠释药系统的研究进展

目的:综述近年来口服结肠释药系统临床和药学研究动态,为今后在此领域的研究和临床应用提供参考。方法:通过对国内外相关文献资料的整理,对比和分析,总结口服结肠释药系统制剂进展和临床应用的发展方向。结果结论:口服结肠释药系统是通过口服给药,在结肠处定位释放药物的靶向制剂。此类制剂以其靶向释药方式和独特的临床使用价值,越来越广泛地引起了临床医生的关注,同时也成为药学研究领域的一大热点。     

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.     

Emerging pressure-release materials for drug delivery

Drug delivery systems for non-specialist uses and application under field conditions are required for medical action in disaster situations and in developing countries. A possible solution for drug delivery under those conditions might be provided by mechanical manipulation of host–guest interactions that could allow drug release control by simple human actions such as hand motion. This editorial article presents recent research developments on control of molecular recognition, capture and release involving macroscopic mechanical motions. In particular, pressure-induced drug release from a cyclodextrin-linked gel has been used to realize controlled release of entrapped drugs upon applying an easy-to-perform mechanical procedure. These easy-action-based drug delivery systems can be applied at will by unskilled staff or patients and are expected to be used to assist medically patients in less-favorable environments anywhere in the world.     

In vitro and in vivo assessment of polymer microneedles for controlled transdermal drug delivery

Microneedles (MNs) system for transdermal drug delivery has the potential to improve therapeutic efficacy, proving an approach that is more convenient and acceptable than traditional medication systems. This study systematically researched dissolving polymer MNs fabricated from various common FDA-approved biocompatible materials, including gelatine, chitosan, hyaluronic acid (HA) and polyvinyl alcohol (PVA). Upon application of MN patches to the porcine cadaver skin, the MNs effectively perforated the skin and delivered drugs to subcutaneous tissue on contact with the interstitial fluid. Both the in vitro and in vivo drug release tests showed the similar trends but different release rates among the prepared MNs. Interestingly, the drug-release kinetics of PVA MNs were able to be altered by changing the molecular weight. To evaluate the feasibility using the proposed MNs for treating diabetes, an in vivo insulin absorption study in diabetic mice was performed. The results showed different insulin release properties of MNs fabricated from various kinds of polymer, leading to different decrease in blood glucose levels. We made a systematic and comprehensive study of some drug-loaded polymer MNs, and anticipated that dissolving polymer MNs have potential to improve therapeutic efficacy through controlled drug release.     

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.     

Janus nanoparticles: materials,preparation and recent advances in drug delivery

Introduction: The term Janus particles was used to describe particles that are the combination of two distinct sides with differences in chemical nature and/or polarity on each face. Due to the exponential growth of interest on multifunctional nanotechnologies, such anisotropic nanoparticles are promising tools in the field of drug delivery.

Areas covered: The main preparation processes and the materials used have been described first. Then a specific focus has been done on therapeutic and/or diagnostic applications of Janus particles.

Expert opinion: Janus particles are demonstrated as interesting objects with advanced properties that combine features and functionalities of different materials in one single unit. Due to their dual structure, Janus particles are promising candidates for a variety of high-quality applications dealing with drug delivery purposes. Still, the main challenges for the future lie in the development of the preparation of shape-controlled and nano-sized particles with large-scale production processes and approved pharmaceutical excipients.     

Development of alpha-lipoic acid encapsulated chitosan monodispersed particles using an electrospray system: synthesis,characterisations and anti-inflammatory evaluations

Abstract

This study demonstrates the feasibility of using a single-capillary electrospray (ES) system to generate novel alpha-lipoic acid encapsulated poly(ethylene oxide)–chitosan (ALA/PEO/CS) particles with a monodispersed diameter. Scanning electron microscopic images (SEM) and dynamic light scattering (DLS) results indicate that the ES system can generate either a dry powder or a homogeneous water-based suspension of ALA/PEO/CS particles. The SEM images revealed that the ALA/PEO/CS particles have a spherical shape with a diameter of approximately 707?±?66.68?nm, and DLS showed that the ALA/PEO/CS particles suspended in deionised water have a diameter of 734.5?nm. In addition, zeta potential studies were performed using a zetasizer instrument and showed positively electric surface potential of 57.7?±?0.5?mV, which was attributed to chitosan. Based on the DLS and zeta potential studies, we concluded that the excellent dispersity and stability of the ALA/PEO/CS suspension is attributed to the reduction in particle size and electrostatic repulsion between these tiny particles. Finally, we used lipopolysaccharide (LPS)-induced nitrite formation in Raw 264.7 macrophages as a model for in vitro anti-inflammation evaluation. We find that the anti-inflammatory ability of the ALA/PEO/CS particles is superior to that of free ALA solution in macrophage cells, which is attributed to the more efficiently intracellular delivery. The confocal image results prove that the uptake of ALA/PEO/CS particles by the LPS-treated Raw 264.7 macrophages is possibly initiated by the interaction with cell-surface molecules through electrostatic interactions, followed by endocytosis of the attached particles.     

Chitosan and its derivatives as vehicles for drug delivery

Abstract

Chitosan and its derivatives as vehicles for drug delivery can achieve the purpose of sustained release and controlled release for drugs, improve the stability of drugs, and reduce adverse drug reactions. So, the bioavailability of drugs can be enhanced. Therefore, chitosan and its derivatives have become a hotspot in the field of drug delivery. Their characteristics as drug delivery vectors were introduced, the types and applications were summarized. The development direction of chitosan and its derivatives in this field was also forecasted.     

Analysis of the Postoperative Periarticular Environment and Influence on Sustained Drug Delivery From a Gel Formulation

Regional intraarticular delivery of local anesthetics is effective in treating postoperative pain following total knee or hip replacement. Recent research efforts have been only partially successful in achieving sustained release of the analgesic agent, in part due to limited understanding of the biological environment into which these formulations are administered. This study aimed to detail the composition and properties of postoperative periarticular fluid (PO-PAF). PO-PAF was collected from 8 patients, and the composition and physicochemical properties were determined. A number of components were identified which are lacking from phosphate buffered saline (PBS) or other synthetic media. The differences in composition led to variation in the physicochemical properties of PO-PAF compared with PBS. Notably, significantly lower surface tension (p <0.05) and higher buffer capacity (p <0.05) were observed in the biological fluid. We demonstrated that the solubility of lidocaine is almost double in PO-PAF compared to PBS (p <0.05) and that lidocaine release from a poloxamer gelling system occurred faster into PO-PAF under both sink and nonsink conditions. Collectively, these data indicate PBS is inappropriate for the in vitro evaluation of intraarticular drug delivery systems. The presented data describe that PO-PAF and will support the future development of biorelevant media to ultimately improve in vivo–in vitro correlation.     

Investigation of the Size Distribution for Diffusion-Controlled Drug Release From Drug Delivery Systems of Various Geometries

Various drug delivery systems (DDSs) are often used in modern medicine to achieve controlled and targeted drug release. Diffusional release of drugs from DDSs is often the main mechanism, especially at early times. Generally, average dimensions of DDS are used to model the drug release, but our recent work on drug release from fibers demonstrated that taking into account diameter distribution is essential. This work systematically investigated the effect of size distribution on diffusional drug release from DDSs of various geometric forms such as membranes, fibers, and spherical particles. The investigation clearly demonstrated that the size distribution has the largest effect on the drug release profiles from spherical particles compared to other geometric forms. Published experimental data for drug release from polymer microparticles and nanoparticles were fitted, and the diffusion coefficients were determined assuming reported radius distributions. Assuming the average radius when fitting the data leads to up to 5 times underestimation of the diffusion coefficient of drug in the polymer.     

Application of pectin in oral drug delivery

Introduction: Biopolymers have been used extensively in the pharmaceutical field. Pectin, a biopolymer, has several unique properties that enable it to be used as an excipient or carrier for oral drug delivery systems. Accordingly, several investigators have identified the benefits of pectin-based delivery systems for oral drug administration.

Areas covered: This review first describes the chemical structure, source and production, degree of esterification and gel formation properties of pectin. The application of pectin in various oral drug delivery platforms is also discussed, that is, controlled release systems, gastro-retentive systems, colon-specific delivery systems and mucoadhesive delivery systems.

Expert opinion: Pectin from different sources provides different gelling abilities, due to variations in molecular size and chemical composition. Like other natural polymers, a major problem with pectin is inconsistency in reproducibility between samples, which may result in poor reproducibility in delivery characteristics. Scintigraphic studies and in vivo studies, in both animals and human volunteers, demonstrate the successful development of a pectin-based colon-specific drug delivery system. Pectin-based controlled release systems, gastro-retentive systems and mucoadhesive systems present promising approaches for increasing the bioavailability of drugs, but are in their infancy. A lack of direct correlation between in vitro release and in vivo absorption studies is a major concern with these systems.     

Drug release kinetics and physicochemical characteristics of floating drug delivery systems

Introduction: Absorption of drugs through the gastrointestinal tract poses a variety of limitations, making the in vivo performance of drug delivery systems uncertain. Following on from recent advances, in a time of increased consideration of floating drug delivery systems, it is as important as ever to continue the progress by studying different aspects of these systems. Moreover, it seems imperative to gain a deeper insight into drug release mechanisms, in order to design a more systematic and intellectual floating system.

Areas covered: This paper summarizes current approaches in the research and development of ideal floating drug delivery systems, from recent literature. Also, in order to have predictability and reproducibility in designing an efficient floating dosage form, some kinetic studies are mentioned, and the drug release mechanism from floating drug delivery systems is discussed.

Expert opinion: Developing an efficient floating dosage form is reliant on a better understanding of the relation between formulation variables and performance of the floating systems. Generally, the combination of two buoyancy mechanisms and gas-generating systems with swellable polymers would be beneficial for obtaining an appropriate floating lag time and duration of buoyancy, which in turn guarantees optimum efficiency of the pharmaceutical dosage form.     

Pulsed drug delivery

Modern drug delivery aims to develop drug delivery systems that are able to meet specific therapeutic requirements. Whereas sustained drug release aims to maintain a constant drug level within the body, pulsed drug delivery intends to release the drug rapidly within a short period of time, as a result of a biological or external trigger, after a specific lag time. This editorial highlights some of the recent advances in new concepts for pulsed drug delivery and proposes some future strategies.