Biodegradable polymeric drug delivery systems

The use of biodegradable polymeric materials as drug carriers is a relatively new dimension in polymeric drug delivery systems. A number of biodegradable or bioerodible polymers, such as poly (lactic/glycolic acid) copolymer, poly(α-amino acid), polyanhydride, and poly (ortho ester) are currently being investigated for this purpose. These polymers are useful for matrix and reservoir-type delivery devices. In addition, when chemical functional groups are introduced to the biodegradable polymer backbone, such as poly (N-(2-hydroxypropy) methacrylamide), the therapeutic agent can be covalently bound directly orvia spacer to the backbone polymer. These polymer/drug conjugates represent another new dimension in biodegradable polymeric drug delivery systems. In this paper, major emphasis is placed on clinical applications of biodegradable polymeric delivery systems. In addition, examples of biodegradable polymeric durg delivery systems currently being investigated will be discussed for the purpose of demonstrating the potential importance of this new field.     

Study of artemisinin nanocapsules as anticancer drug delivery systems

Artemisinin (ART) crystals were encapsulated with chitosan, gelatin, and alginate for the purpose of controlled release. These polyelectrolytes were alternatively deposited on ART crystals sized about 766 nm through the layer-by-layer technique. Size distribution, zeta potential, and swelling property of ART nanocapsules were measured. The morphology of ART nanocapsules was observed by transmission electron microscopy after dissolution. Release property of ART nanocapsules was measured in phosphate buffer solution (pH 7.4). It was proved that the ART nanocapsules dispersed well in aqueous solutions. Hydrophilicity of ART crystals was improved after encapsulation. The ART drug release rate was tuned by the properties of polyelectrolyte solutions, such as polyelectrolyte type, number of polyelectrolyte multilayers, sodium chloride concentration, and ethanol concentration in polyelectrolyte solution, and so on. Our research provides a feasible method of achieving prolonged drug release through self-assembly of polyelectrolytes on natural drug crystals.From the Clinical EditorArtemisinin (ART) crystals were encapsulated with chitosan, gelatin, and alginate for the purpose of controlled release of this anticancer drug. The reported method is feasible for achieving prolonged drug release through self-assembly of polyelectroytes on natural drug crystals.     

Applications of biomimetic systems in drug delivery

This review article highlights recent activities in the field of biomimetic systems and their application in controlled drug delivery. A definition and overview of biomimetic processes is given, with a focus on synthesis and assembly for the creation of novel biomaterials. In particular, systems are classified on the basis of three subsets, which include biological, biohybrid and synthetic structures. Examples focus on the current and proposed clinical significance for systems that mimic processes where the underlying molecular principles are well understood. Biomimetic materials and systems are presented as exceptional candidates for various controlled drug delivery applications and have enormous potential in medicine for the treatment of disease.     

Applications of biomimetic systems in drug delivery

This review article highlights recent activities in the field of biomimetic systems and their application in controlled drug delivery. A definition and overview of biomimetic processes is given, with a focus on synthesis and assembly for the creation of novel biomaterials. In particular, systems are classified on the basis of three subsets, which include biological, biohybrid and synthetic structures. Examples focus on the current and proposed clinical significance for systems that mimic processes where the underlying molecular principles are well understood. Biomimetic materials and systems are presented as exceptional candidates for various controlled drug delivery applications and have enormous potential in medicine for the treatment of disease.     

Implantable,polymeric systems for modulated drug delivery

The ability to deliver therapeutic agents to a patient in a pulsatile or staggered release profile has been a major goal in drug delivery research over the last two decades. This review will cover methods that have been developed to control drug delivery profiles with implantable polymeric systems. Externally and internally controlled systems will be discussed, spanning a range of technologies that include pre-programmed systems, as well as systems that are sensitive to modulated enzymatic or hydrolytic degradation, pH, magnetic fields, ultrasound, electric fields, temperature, light and mechanical stimulation. Implantable systems have the potential to improve the quality of life for patients undergoing therapy with a variable dosing regime by eliminating the need for multiple intravenous injections. Ideally, these systems would also result in increased patient compliance with a given therapy due to the relative ease of self-dosing.     

Applications of nanoparticle systems in drug delivery technology

The development of nanoparticle-based drug formulations has yielded the opportunities to address and treat challenging diseases. Nanoparticles vary in size but are generally ranging from 100 to 500?nm. Through the manipulation of size, surface characteristics and material used, the nanoparticles can be developed into smart systems, encasing therapeutic and imaging agents as well as bearing stealth property. Further, these systems can deliver drug to specific tissues and provide controlled release therapy. This targeted and sustained drug delivery decreases the drug related toxicity and increase patient’s compliance with less frequent dosing. Nanotechnology has proven beneficial in the treatment of cancer, AIDS and many other disease, also providing advancement in diagnostic testing.     

生物可降解纳米药物转运系统研究进展

纳米药物载体有延长药物作用时间、增加疗效、降低毒副作用、缓控释给药等优点。而生物可降解高分子材料因其良好的生物利用度、载药能力和控释能力以及较低的毒性而被广泛用于纳米药物。本文综述了聚乳酸-羟基乙酸共聚物(PLGA)、聚乳酸(PLA)、聚己内酯(PCL)高分子化合物制备纳米粒的合成和载药方法及应用。     

Mathematical modeling of bioerodible, polymeric drug delivery systems

The aim of this article is to give an introduction into mathematical modeling approaches of bioerodible controlled drug delivery systems and to present the most important erosion theories reported in the literature. First, important parameters such as degradation and erosion are defined and physicochemical methods for their investigation are briefly presented. Then, phenomenological empirical models as well as models based on diffusion and chemical reaction theory are discussed. Due to the significant chemical and physicochemical differences among individual bioerodible polymers used for controlled drug delivery systems, various mathematical models have been developed to describe the chemical reactions and physical mass transport processes involved in erosion-controlled drug release. Various examples of practical applications of these models to experimental drug release data are given. For those involved in the design and development of biodegradable drug delivery systems this will help to choose the appropriate mathematical model for a specific drug release problem. Important selection criteria such as the desired predictive power and precision, but also the effort required to apply a model to a particular system will be discussed. Furthermore, before models can be used for drug release predictions certain parameters such as drug dissolution or polymer degradation rate constants, have to be known. The number of parameters to be determined significantly differs between the models. The practical benefit of carefully choosing the right model is that effects of composition and device geometry on the drug release kinetics can be predicted which can reduce laborious formulation studies to a minimum.     

Intelligent drug delivery systems: polymeric micelles and hydrogels

Advanced drug delivery systems try to adjust the site and/or the rate of the release to the physiological conditions of the patient, to the progression of the illness, or to the circadian rhythms. Being different from classical pre-programmed controlled release dosage forms, the new devices aim to provide the drug release profile best for the needs of each patient. Intelligent drug delivery systems are mostly based on stimuli-responsive polymers which sense a change in a specific variable and activate the delivery; this phenomenon being reversible. This review reports on recent advances in the development of open-loop and closed-loop control systems based on stimuli-responsive polymers and their application in the drug delivery field as pulsatile and self-regulated devices. The aim of this review is to describe the most recent advances in the development of intelligent micelles and hydrogels which are sensitive to pH, specific molecules (with a mention to the molecular imprinting), temperature, irradiation or electric field, and the applications of which these mechanisms are intended.     

Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems

The objective of this research was to examine the human sub-bronchial gland cell line, Calu-3, and assess its potential as a metabolic and transport model to study drug delivery to the respiratory epithelium. The present studies were conducted using Calu-3 cells grown in Transwells(R) or in multiwell cluster plates. TEER values for Calu-3 monolayers were determined using the World Precision Instrument Voltohmmeter and STX-2 electrode. The results confirmed that Calu-3 cells form tight monolayers and give appreciable TEER values in culture when grown under air-interface conditions. Permeability data for small lipophilic molecules across Calu-3 monolayers suggested that the cell line is a suitable model to examine the transport of low molecular weight substances and xenobiotics. Calu-3 cells were also found to efflux FITC-transferrin (MW 80000) in a polarized manner. The metabolic capacity of Calu-3 cells was also examined. The P4501A1 and P4502B isozymes were determined to be functional, but not inducible, with fluorescent resorufin assays. The data indicated that the Calu-3 cell line may be useful for studying the contributions of bronchial epithelial cells to mechanisms of drug delivery at the respiratory epithelium.     

Responsive polymeric delivery systems

This paper discusses the state of the art in a relatively new approach in the field of controlled drug delivery-responsive polymeric drug delivery systems. Such systems are capable of adjusting drug release rates in response to a physiological need. The fundamental principles of externally and self-regulated delivery systems are examined. Special attention is paid to specific clinical settings such as diabetes, presenting the advantages and disadvantages of different approaches.     

Responsive polymeric delivery systems

This paper discusses the state of the art in a relatively new approach in the field of controlled drug delivery–responsive polymeric drug delivery systems. Such systems are capable of adjusting drug release rates in response to a physiological need. The fundamental principles of externally and self-regulated delivery systems are examined. Special attention is paid to specific clinical settings such as diabetes, presenting the advantages and disadvantages of different approaches.     

Synthesis of nanocapsules blended polymeric hydrogel loaded with bupivacaine drug delivery system for local anesthetics and pain management

Local anesthetics are used clinically for the control of postoperative pain management. This study aimed to develop chitosan (CS) with genipin (GP) hydrogels as the hydrophilic lipid shell loaded poly(ε-caprolactone) (PC) nanocapsules as the hydrophobic polymeric core composites (CS-GP/PC) to deliver bupivacaine (BPV) for the prolongation of anesthesia and pain relief. The swelling ratio, in vitro degradation, and rheological properties enhancement of CS-GP/PC polymeric hydrogel. The incorporation of PC nanocapsules into CS-GP hydrogels was confirmed by SEM, FTIR, and XRD analysis. Scanning electron microscopy results demonstrated that the CS-GP hydrogels and CS-GP/PC polymeric hydrogels have a porous structure, the pore dimensions being non-uniform with diameters between 25 and 300 μm. The in vitro drug release profile of CS-GP/PC polymeric hydrogel has been achieved 99.2 ± 1.12% of BPV drug release in 36 h. Cellular viability was evaluated using the CCK-8 test on 3T3 fibroblast cells revealed that the obtained CS-GP/PC polymeric hydrogel with BPV exhibited no obvious cytotoxicity. The CS-GP/PC polymeric hydrogel loaded with BPV showed significant improvement in pain response compared to the control group animals for at least 7 days. When compared with BPV solution, CS-GP hydrogel and CS-GP/PC polymeric hydrogel improved the skin permeation of BPV 3-fold and 5-fold in 24 h, respectively. In vitro and in vivo results pointed out PC nanocapsules loaded CS-GP hydrogel can act as effective drug carriers, thus prolonging and enhancing the anesthetic effect of BPV. Histopathological results demonstrated the excellent biodegradability and biocompatibility of the BPV-loaded CS-GP/PC polymeric hydrogel system on 7, 14, and 21 days without neurotoxicity.

HIGHLIGHTS

• Preparation and characterization of CS-GP/PC polymeric hydrogel system.
• BPV-loaded CS-GP/PC exhibited prolonged in vitro release in PBS solution.
• Cytotoxicity of BPV-loaded CS-GP/PC polymeric hydrogel against fibroblast (3T3) cells.
• Development of CS-GP/PC a promising skin drug-delivery system for local anesthetic BPV.

     

聚合物胶束递药系统逆转肿瘤多药耐药性的研究进展

聚合物胶束是近年来抗肿瘤药物递药系统研究中发展较快的一种新型递药载体,可显著提高药物抗肿瘤效果,尤其在逆转肿瘤多药耐药现象方面表现出极大的潜在价值。本文主要综述了聚合物胶束递药系统抑制肿瘤多药耐药现象的过程和机制,总结了该领域研究的最新进展,以期为聚合物胶束递药系统今后在该领域的研究提供参考。     

In vivo and in vitro release of macromolecules from polymeric drug delivery systems

In vivo release rates of a macromolecule from an ethylene-vinyl acetate copolymer have been shown to be indistinguishable from those of identical implants tested in vitro. The studies were conducted for approximately 2 months, and two different techniques were used to assess release rates. One of these techniques, using [3H]inulin as a marker, may be particularly useful in future studies assessing in vivo release rates from drug delivery systems. The appearance of [3H]inulin in the urine of rats bearing implants allowed continuous monitoring of release. A histological evaluation of tissue sections surrounding polymer implanted for 7 months showed no inflammatory cell reaction.     

Preparation and characterization of nanocapsules for colon-targeted drug delivery system

Context: Nanoparticles for colon-specific drug delivery system are known for their specific accumulation in the inflamed tissue in the colon and may therefore allow a selective delivery to the site of inflammation for the treatment of inflammatory bowel disease (IBD).

Objective: The objective of this study was to formulate and evaluate nanocapsules (NC), an oral system designed to achieve site-specific and instant drug release in colon for effective treatment of IBD.

Materials and methods: Prednisolone (PD), a typical glucocorticoid, has been widely used for the treatment of IBD. In this study, nanoprecipitation method was used to prepare polymeric NC of PD with pH responsive polymer Eudragit S100. The effect of several formulation variables such as surfactant, oil, and polymer on the PD-NC properties (average size, drug release rate, and drug entrapment) was investigated. In vitro drug release study was done by changing pH method and an in vivo study on rat was done to ascertain efficiency of PD-NC to release drug specifically in colon.

Results and discussion: The optimized formulations lead to the preparation of PD-NC with a mean size of 567.87?nm, high encapsulation efficiency of 90.21%. In vitro studies reveal that NC releases the drug after 4.5-h lag time corresponding to time to reach colonic region, and in vivo studies show that NC release drug after 3-h lag time in rat corresponds to arrival in colon.

Conclusion: The above NC formulation of PD is the targeted drug to the colon and may provide effective way of treatment of colonic disease.     

Recent progress in polymeric gene delivery systems

Considerable progress in polymeric gene delivery systems has been made over the last several years. First generation polymers have been replaced by safer and more efficient carrier systems through molecular functionalization, improving polymer biocompatibility, biological stability, cell-specificity, and intracellular trafficking. Many new polymers have moved from in vitro characterization to preclinical validation in animal models of cancer, diabetes, and cardiovascular disorders. Although the transfection efficiency of most polymeric carriers is still significantly lower than that of viral vectors, their structural flexibility allows for continued improvement in polymer activity. Also, simple manufacturing and scale-up schemes and the low cost of manufacturing are likely to eventually compensate for the performance gap between viral and polymeric vectors and establish clinical recognition and commercialization of polymer-based gene therapy drugs.