Electro-responsive transdermal drug delivery behavior of PVA/PAA/MWCNT nanofibers

The electro-responsive transdermal drug delivery system was prepared by electrospinning of poly(vinyl alcohol)/poly(acrylic acid)/multi-walled carbon nanotubes (MWCNTs) nanocomposites. The surface modification of MWCNTs was carried out by oxyfluorination to introduce the functional groups on the hydrophobic MWCNTs. The dispersion of MWCNTs and the compatibility with polymer matrices were improved by oxyfluorination. The MWCNT content and oxyfluorination condition played important roles in the swelling and drug release characteristics of nanofibers. The conductivity of nanofibers increased by increasing the content of MWCNTs and performing oxyfluorination with higher oxygen content. Uniform distribution of the oxyfluorinated MWCNTs in the nanofibers was crucial to the electro-responsive swelling and drug releasing behaviors of nanofibers.     

Iontophoretic transdermal drug delivery system using a conducting polymeric membrane

This work investigated the application of a porous polyaniline (PANi) membrane as a conducting polymeric membrane as well as an electrode in an iontophoretic transdermal drug delivery (TDD) system. Model drugs studied were: caffeine (MW: 194.2), lidocaine HCl (MW: 270.8) and doxycycline HCl (MW: 480.1). The PANi membrane was first tested as a simple membrane between the donor and receptor solutions; it provided satisfactory permeation profiles; the observed flux values were well described by a simplified mass transport model. A mouse skin was then mounted beneath the PANi film; such a composite system also presented satisfactory permeation profiles. Iontophoretic TDD experiments were next performed using both Ag|AgCl electrodes and PANi|AgCl electrodes for comparison; a PANi anode replaced the Ag anode in the last set. For doxycycline HCl, the flux and the 24-h accumulation from the PANi|AgCl set were 94.4 ± 81.2 μg/cm² h and 2760 ± 3980 μg/cm², respectively; those from the Ag|AgCl set were zero. For lidocaine HCl, the flux and 10-h accumulation from the PANi|AgCl set were, respectively, 43 ± 15 μg/cm² h and 392 ± 130 μg/cm²; the corresponding values from the Ag|AgCl set were 48 ± 20 μg/cm² h and 348 ± 78 μg/cm². Porous polyaniline membrane appears to be capable of replacing the Ag part of Ag|AgCl electrode system; further such a membrane can exercise additional control over agent transport rate. Aqueous-organic partitioning system through the porous membrane of PANi was tested with this novel technique as well. Because of the rather low porosity of the synthesized PANi film, such a system did not yield a high permeation rate.     

Pectin in controlled drug delivery – a review

Controlled drug delivery remains a research focus for public health to enhance patient compliance, drug efficiency and reduce the side effects of drugs. Pectin, an edible plant polysaccharide, has been shown to be useful for the construction of drug delivery systems for specific drug delivery. Several pectin derived formulations have been developed in our laboratory and tested in vitro, ex vivo, and in vivo for the ability to deliver bioactive substances for therapeutic purposes in the context of interactions with living tissues. Pectin derivatives carrying primary amine groups were more mucoadhesive and have shown potential in nasal drug delivery and other mucosal drug delivery. Pectin derivatives with highly esterified galacturonic acid residues are more hydrophobic and able to sustain the release of incorporated fragrances for a prolonged duration. Less esterified pectin derivatives are able to penetrate deeper into the skin and may be useful in aromatherapy formulations. Pectin, in combination with zein, a corn protein, forms hydrogel beads. The bound zein restricts bead swelling and retains the porosity of the beads; the pectin networks shield the zein from protease attack. The complex beads are ideal vehicles for colon-specific drug delivery. Studies presented in this paper indicate the flexibility and possibility to tailor pectin macromolecules into a variety of drug delivery systems to meet different clinical requirements. Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture.     

A new poly(2-hydroxy-3-phenoxypropylacrylate, 4-hydroxybutyl acrylate, diethyl maleate) membrane controlled clonidine linear release in the transdermal drug delivery system

Oral clonidine, used as an antihypertensive, can result in some side effects such as dry mouth, drowsiness, dizziness and sedation; thus, clonidine transdermal drug delivery (TDD) was considered. Use of the controlled release membrane was one of the methods in TDD systems to regulate the permeation properties. A new type of copolymer membrane that controlled clonidine linear release in TDD system was synthesized by UV radiation. This membrane consisted of three monomers: 2-hydroxy-3-phenoxypropylacrylate, 4-hydroxybutyl acrylate and diethyl maleate. The membrane had both fine permeation properties and perfect physical properties when three monomers were in the weight ratio of 4:4:2; this type of membrane was chosen as an optimized membrane. It was found that the membrane controlled clonidine zero-order release, the permeation rates decreased with the thicknesses of membranes increasing, and the permeation rates were linearly dependent on the square root of the concentration of clonidine. Furthermore, the optimized membranes were characterized by FTIR, DSC and SEM.     

Progress in natural polymer engineered biomaterials for transdermal drug delivery systems

The route of a specific drug carrier system is always a significant platform of development that combines the principles of biomedical technology, nanotechnology, and pharmaceutical drug design. Transdermal (TD) drug delivery involves the release of the drug via the stratum corneum of the tissue membrane into the sustained release by diffusion across the epidermal layer. This method (often known as topical drug delivery) has increased noteworthy research enthusiasm in the course of recent decades due to its relatively simpler and non-invasive administration. Over the past few decades, considerable advancement was achieved in TD delivery and a number of drugs are now successfully reported. In this review, we focus on the progress regarding applications of important biopolymers described for the TD drug release applications and related aspects. Three mostly reported plant and animal-derived polymers (such as natural rubber, chitosan, and cellulose for the development of TD carrier system) were extensively analyzed. The general principle of TD drug delivery, advantages, and limitations of the works reported were also discussed.     

Bigels: A unique class of materials for drug delivery applications

Bigels, combination of organogel and hydrogel, are unique solid-like formulations with improved properties for food, cosmetics, and pharmaceutical applications. Bigel possesses merits of both phases, aqueous and oily, and displays better properties than either of the single gel. The uniqueness of bigels comes from their ability to deliver both hydrophilic and lipophilic active agents, enrichment of hydration of stratum corneum, easily spreadable, and so on. The main objective of this review article is to provide a thorough insight into the classification of bigels on the basis of synthesis method and morphology and also to demonstrate the detailed analysis of bigel formulations by considering different characterization techniques. Moreover, a special focus is given on the applications of bigels as drug delivery vehicles by transdermal route.     

普鲁兰多糖在药物释放系统中的应用

本综述重点介绍了近年来普鲁兰多糖作为药物释放系统载体材料的研究进展及其在药物释放系统中的应用情况。     

Electro-responsive polyacrylamide-grafted-gum ghatti copolymer for transdermal drug delivery application

An application of polyacrylamide-grafted-gum ghatti (PAAm-g-GGH) copolymer for transdermal delivery of an anti-psychotic drug, quetiapine fumerate triggered by electric stimulus was explored. The electro-responsive PAAm-g-GGH was prepared by free radical polymerization underneath nitrogen atmosphere subsequent to alkaline hydrolysis. The PAAm-g-GGH was used as drug reservoir gel and crosslinked films of GGH and PVA as rate controlling membranes (RCM). The reservoir gels were uniform and translucent; pH of gels was 6.56–7.06, which is in the pH range of skin and drug content was from 89.57% to 94.51%. The thickness of RCMs was 163–227?μ; thickness was increased with increased glutaraldehyde concentration and all the RCMs were permeable to water vapors. When electric stimulus was absent, a small amount of drug was permeated from the formulations, while drug conveyance was enhanced in the existence of stimulus. Drug permeation was increased with increase in electric stimulus from 2 to 8?mA. Over two fold increase in flux was observed after application of electric stimulus. Under “on–off” electric stimulus, faster drug permeation was seen under ‘on’ condition and permeation was decreased when stimulus was ‘off.’ Histopathology study confirmed reversible alteration of skin structure under electric stimulus.     

Biopolymer based nanomaterials in drug delivery systems: A review

Drug delivery systems (DDS) are used to achieve a higher therapeutic effects of a pharmaceutical drug or natural compound in a specific diseased site with minimal toxicological effect and these systems consists of liposomes, microspheres, gels, prodrugs and many. Nanotechnology is a rapidly developing multi-disciplinary science that ensures the fabrication of the polymers to nanometer scale for various medical applications. Uses of biopolymers in DDS ensure the biocompatibility, biodegradability and low immunogenicity over the synthetic ones. Biopolymers such as silk fibroins, collagen, gelatin, albumin, starch, cellulose and chitosan can be easily made into suspension that serve as delivery vehicles for both macro and mini drug molecules. There are various methods such as supercritical fluid extraction, desolvation, electrospraying, spray-drying, layer-by-layer self-assembly, freeze-drying and microemulsion introduced to make these DDS. This drug carrier systems enhance the drug delivery actively and can be used in ocular, transdermal, dental or intranasal delivery systems. This review describes the new trends in nanomaterials based drug delivery systems mainly using biopolymers such as proteins (silk fibroin, collagen, gelatin and albumin) and polysaccharides (chitosan, alginate, cellulose and starch).     

Polypeptide dendrimers: Self-assembly and drug delivery

Amphiphilic dendritic poly(glutamic acid)-b-polyphenylalanine copolymers were synthesized using generation 3 dendritic poly(glutamic acid) as the macroinitiator in the ring-opening polymerization of NCA-Phe.The block copolymers self-assembled micelles with polyphenylalanine segments as core and dendritic poly(glutamic acid) segments as shell.The biocompatibility of the micelles was studied.The release of the anticancer drug doxorubicin from the micelles was investigated in vitro.The results showed that the ...     

Micelles from amphiphilic block copolyphosphates for drug delivery

Amphiphilic block copolyphosphates (PEP-b-PIPPs) are synthesized by two-step ROP of cyclic phosphate monomers with different pedant groups. They can spontaneously self-assemble into approximately spherical micelles ranging in size between 89 and 198 nm in water. A typical hydrophobic anti-cancer drug DOX is encapsulated into the micelles. The release rate of DOX slows down with increasing hydrophobic block length of PIPP. DOX-loaded micelles are investigated for the proliferation inhibition of Hela cells and the DOX dose required for 50% cellular growth inhibition is found to be 0.8 μg mL(-1). It is demonstrated that PEP-b-PIPP micelles can be used as a safe and promising drug delivery system.     

肽类树枝状大分子:自组装胶束及药物释放研究

本文以三代聚谷氨酸肽类树枝状分子(G3-Glu)为大分子引发剂,引发N-羧基-L-苯丙氨酸-环内酸酐(NCA-Phe)的开环聚合反应,制备聚谷氨酸树枝状大分子-聚苯丙氨酸嵌段共聚物.嵌段共聚物通过自组装形成以聚苯丙氨酸链段为核,聚谷氨酸树枝状大分子为壳的胶束.将抗肿瘤药物阿霉素负载到高分子胶束中,研究其药物释放性能及体外抗肿瘤效果.结果表明,共聚物胶束具有良好的生物相容性.载药胶束具有药物缓释效果,药物持续释放时间可达60h.载药胶束的体外抗肿瘤实验表明其对肝癌细胞HepG2具有很好的杀灭效果,共培养48h后对癌细胞的杀死率可高达75%.     

Microneedle-based electrochemical devices for transdermal biosensing: a review

Many research efforts over the last decade have been devoted to the development of microneedle-based diagnostic devices for minimally invasive transdermal biosensing and for long-term health monitoring. Transdermal biosensing via microneedle allows the development of minimally invasive easy-to-use point-of-care biodevices. The main objective of this short review is to provide a general overview of the most immediate and relevant progress in microneedle-based transdermal biosensing in the last five years. A critical analysis of the recent literature is finally presented.     

Dendritic polyurethane-based prodrug as unimolecular micelles for precise ultrasound-activated localized drug delivery

Ultrasound has been recognized as an exciting tool to enhance the therapeutic efficacy in tumor chemotherapy owing to the triggered drug release, facilitated intracellular drug delivery, and improved spatial precision. Aiming for a precise localized drug delivery, novel dendritic polyurethane-based prodrug (DOX-DPU-PEG) was fabricated with a drug content of 18.9% here by conjugating DOX onto the end groups of the functionalized dendritic polyurethane via acid-labile imine bonds. It could easily form unimolecular micelles around 38 nm. Compared with the non-covalently drug-loaded unimolecular micelles (DOX@Ph-DPU-PEG), they showed excellent pH/ultrasound dual-triggered drug release performance, with drug leakage of only 4% at pH 7.4, but cumulative release of 14% and 88% at pH 5.0 without and with ultrasound, respectively. The ultrasound responsiveness was attributed to the unique strawberry-shaped topological structure of the DOX-DPU-PEG, in which DOX was embedded in the skin layer of the hydrophobic DPU cores. With ultrasound, the DOX-DPU-PEG unimolecular micelles possessed enhanced tumor growth inhibition than free DOX but showed no obvious cytotoxicity on the tumor cells without ultrasound. Such feature makes them promising potential for precise localized drug delivery.     

Synthesis and characterization of an acrylate pressure sensitive adhesive for transdermal drug delivery

The present investigation was directed towards the synthesis of a copolymer of 2‐ethylhexyl acrylate and acrylic acid to be exploited as a pressure sensitive adhesive (PSA) matrix in transdermal drug delivery systems. The polymer synthesis involved free radical solution polymerization using 2, 2′‐azobisisobutyronitrile as the free radical initiator. The experimental methodology involved the optimization of reaction conditions for the polymer synthesis. The optimized copolymer was then characterized by IR, ¹H‐NMR, DSC, GPC and XRD. The PSA was also evaluated for percent free monomer content, intrinsic viscosity, refractive index, moisture uptake potential and film forming properties. To assess it suitability in the development of transdermal systems, peel strength values with respect to release liner as well as human skin and skin irritation potential were also determined. In addition, wear performance test was conducted to evaluate adhesion and adhesive transfer. The synthesized adhesive was found to have good peel strength; exhibited excellent adhesion and adhesive transfer on removal. It was found suitable for use in transdermals and could be further exploited either as an adhesive matrix or as a system component in the area of transdermal drug delivery. Copyright © 2002 John Wiley & Sons, Ltd.     

Mesoporous materials for drug delivery

Research on mesoporous materials for biomedical purposes has experienced an outstanding increase during recent years. Since 2001, when MCM-41 was first proposed as drug-delivery system, silica-based materials, such as SBA-15 or MCM-48, and some metal-organic frameworks have been discussed as drug carriers and controlled-release systems. Mesoporous materials are intended for both systemic-delivery systems and implantable local-delivery devices. The latter application provides very promising possibilities in the field of bone-tissue repair because of the excellent behavior of these materials as bioceramics. This Minireview deals with the advances in this field by the control of the textural parameters, surface functionalization, and the synthesis of sophisticated stimuli-response systems.     

Film‐ and ointment‐based delivery systems for the transdermal delivery of TNP‐470

Pathological angiogenesis, the process of new blood vessel formation, is responsible for a broad range of neovascular‐related systemic diseases. One of the first antiangiogenic compounds tested in clinical trials against cancer was TNP‐470. Despite promising activity the injectable drug showed poor plasma stability and caused adverse side effects in high doses lead to termination of the trials. In our current work, we introduce the development of a transdermal delivery systems for controlled release of TNP‐470. Such formulation can potentially reduce toxicity due to controlled continuous dosing and improve stability by avoiding gastrointestinal first pass metabolism. Although transdermal delivery is a very challenging route for drug administration due to the low permeability of the skin, here we present a successful development of two different drug delivery systems, film and ointment for dermal application of TNP‐470. Chitosan film had high loading capacity of up to 50% w/w of TNP‐470 compared with 10% maximum loading in hydrocarbon ointment. A detailed step‐by‐step development of TNP‐470 films, from the initial solvent screening to final optimized formulation, is presented. Ex vivo skin permeation studies demonstrated a superior release of the drug from the film formulation compared with the ointment. Furthermore, histological test of the skin confirmed ointment safety showing no evidence of skin tissues damage. Our results present novel, promising, controlled release drug delivery systems with improved stability, efficacy, and safety profile of TNP‐470 via transdermal route.