Gene delivery using functional dendritic polymers

Objective: This review describes a strategy for the development of multifunctional dendritic polymers for application as gene delivery systems. These polymers can address the low transfection efficiency usually encountered by synthetic non-viral vectors. Methods: Employing appropriate, well-characterized and mainly commercially available dendritic polymers, the emphasis is placed primarily on step-wise molecular engineering of their surface for providing gene carriers of low toxicity, specificity to certain cells and transport ability through their membranes, with the ultimate objective of enhanced transfection efficiency. Cationic dendritic polymers interact with appropriate genetic material, affording complexes that are employed for cell transfection. Conclusion: Multifunctionalization of dendritic polymers provides gene vectors of low toxicity, significant transfection efficiency, specificity to certain biological cells and transport ability through their membranes.     

Current knowledge on biodegradable microspheres in drug delivery

Introduction: Biodegradable microspheres have gained popularity for delivering a wide variety of molecules via various routes. These types of products have been prepared using various natural and synthetic biodegradable polymers through suitable techniques for desired delivery of various challenging molecules. Selection of biodegradable polymers and technique play a key role in desired drug delivery.

Areas covered: This review describes an overview of the fundamental knowledge and status of biodegradable microspheres in effective delivery of various molecules via desired routes with consideration of outlines of various compendial and non-compendial biodegradable polymers, formulation techniques and release mechanism of microspheres, patents and commercial biodegradable microspheres.

Expert opinion: There are various advantages of using biodegradable polymers including promise of development with different types of molecules. Biocompatibility, low dosage and reduced side effects are some reasons why usage biodegradable microspheres have gained in popularity. Selection of biodegradable polymers and formulation techniques to create microspheres is the biggest challenge in research. In the near future, biodegradable microspheres will become the eco-friendly product for drug delivery of various genes, hormones, proteins and peptides at specific site of body for desired periods of time.     

Effects of pH-sensitive nanoparticles prepared with different polymers on the distribution,adhesion and transition of Rhodamine 6G in the gut of rats

To investigate the effect of different enteric polymers on the characteristics of pH-sensitive nanoparticles, Rhodamine 6G (Rho) was incorporated in various pH-sensitive nanoparticles. The different patterns of pH-dependent release profiles were observed, although some polymers have the same dissolving pH. The distribution, adhesion and transition of different nanoparticles in rat gut showed significant difference, closely related to the release characteristics of nanoparticles, and their release behaviour are dependent on the dissolving pH and the structure of the polymers, as well as the drug property. Most nanoparticle formulations decreased the distribution and adhesion of Rho in the stomach but increased these values in the intestine. The nanocarriers also control the drug release sites and release rate in the GI tract. In conclusion, pH-sensitive nanoparticles seem favourable for drug absorption and it is important to choose the proper materials to obtain the suitable characteristics for the oral pH-sensitive nanoparticles.     

Development of a microencapsulated form of cefuroxime axetil using pH-sensitive acrylic polymers

Abstract

Cefuroxime axetil (CA) was encapsulated in pH-sensitive acrylic micro spheresin order to formulate a suspension dosage form. Using this microencapsulated form it was expected to prevent leaching of the drug from the micro spheresinto the suspension medium and to assure the release of the drug in the first part of the intestinethus avoiding changes to its bioavailability. For this purpose CA was microencapsulated within several types of acrylic polymers by the solvent evaporation and the solvent extraction techniques., The acrylic polymers selected were: Eudragit E (positively charged and soluble at pH 5)Eudragit L-55 (negatively charged and soluble at pH >5.5) and Eudragit RL (neutralinsolublebut readily permeable)., The influence of the polymer electrical charge on the stability and in vitro release of CA was investigated., Though Eudragit E micro spherespresented good morphological characteristics and dissolution behaviourthe analysis of the stability of CA in the presence of Eudragit E by HPL Cindicated a negative interaction between both compounds., Howeverformulations made of Eudragit L-55 and RL in the ratios 100:0 and 90:10 were adequate in terms of the stability of the encapsulated CA., The dissolution studies showed a critical pH between 5.2 and 6.0which allowed the complete release of CA in a short period., Furthermorethese polymer micro sphereswere shown to be efficient in masking the taste of CA.     

Nanoparticle-based immunopotentiation via tetanus toxoid-loaded gelatin and aminated gelatin nanoparticles

Gelatin nanoparticles (GNPs) and aminated gelatin nanoparticles (AGNPs) were prepared and used as an adjuvant to improve the delivery of tetanus toxoid (TT). Nanoparticles were characterized in vitro for their size, shape, entrapment, and release. TT-FITC conjugate was used to determine entrapment and release from nanoparticles. The immune-stimulating activity was studied by measuring anti-TT IgG, IgG1, and IgG2a isotype and cytokine responses following subcutaneous (s.c) injection of nanoparticles in BALB/c mice and was compared with alum-TT vaccine. Gelatin and aminated gelatin (AG) specific IgG response was also determined. Both GNPs and AGNPs demonstrated comparable IgG response and a significantly higher (p?<?0.05) cytokine response (IL-2 and IFN γ) as compared to alum-TT vaccine. Nanoparticulate formulations elicited both Th1 and Th2 responses and induced negligible undesirable immunogenicity against the carrier, as demonstrated by lower level of gelatin and AG-specific IgG response as compared to control.     

天然高分子磁微球作为靶向制剂的研究进展

磁性微球作为靶向药物载体有利于提高药物疗效，降低药物的毒副作用，为化疗药物的临床应用开辟了新途径。文章着重综述和评价了以天然高分子材料为载体的磁性微球的制备和应用，并对相关研究工作中存在的问题提出了看法。     

ICS-283: a system for targeted intravenous delivery of siRNA

ICS-283 was developed within Intradigm Corporation as a system that is designed for the systemic delivery of therapeutic small interfering (siRNA) to sites of pathological angiogenesis. The non-viral siRNA delivery system is based on synthetic nanoparticles, known as TargeTran? (Intradigm Corporation), which functions as a broad-platform technology to deliver siRNA to specific target cells in diseased tissues. The system is constructed to incorporate different functionalities that address critical needs for successful nucleic acid delivery. The TargeTran synthetic vector is a self-assembling, layered nanoparticle that protects and targets siRNA to specific cell types in pathological tissues. At present, ICS-283 is the only antiangiogenic siRNA delivery system that is designed for intravenous administration to treat angiogenesis-driven diseases.     

Biopharmaceutical formulations for pre-filled delivery devices

Introduction: Pre-filled syringes are becoming an increasingly popular format for delivering biotherapeutics conveniently and cost effectively. The device design and stable liquid formulations required to enable this pre-filled syringe format are technically challenging. In choosing the materials and process conditions to fabricate the syringe unit, their compatibility with the biotherapeutic needs to be carefully assessed. The biothereaputic stability demanded for the production of syringe-compatible low-viscosity liquid solutions requires critical excipient choices to be made.

Areas covered: The purpose of this review is to discuss key issues related to the stability aspects of biotherapeutics in pre-filled devices. This includes effects on both physical and chemical stability due to a number of stress conditions the product is subjected to, as well as interactions with the packaging system. Particular attention is paid to the control of stability by formulation.

Expert opinion: We anticipate that there will be a significant move towards polymer primary packaging for most drugs in the longer term. The timescales for this will depend on a number of factors and hence will be hard to predict. Formulation will play a critical role in developing successful products in the pre-filled syringe format, particularly with the trend towards concentrated biotherapeutics. Development of novel, smart formulation technologies will, therefore, be increasingly important.     

Drug-releasing shape-memory polymers – the role of morphology,processing effects,and matrix degradation

Introduction: Shape-memory polymers (SMPs) have gained interest for temporary drug-release systems that should be anchored in the body by self-sufficient active movements of the polymeric matrix.

Areas covered: Based on the so far published scientific literature, this review highlights three aspects that require particular attention when combining SMPs with drug molecules: i) the defined polymer morphology as required for the shape-memory function, ii) the strong effects that processing conditions such as drug-loading methodologies can have on the drug-release pattern from SMPs, and iii) the independent control of drug release and degradation by their timely separation.

Expert opinion: The combination of SMPs with a drug-release functionality leads to multifunctional carriers that are an interesting technology for pharmaceutical sciences and can be further expanded by new materials such as thermoplastic SMPs or temperature-memory polymers. Experimental studies should include relevant molecules as (model) drugs and provide a thermomechanical characterization also in an aqueous environment, report on the potential effect of drug type and loading levels on the shape-memory functionality, and explore the potential correlation of polymer degradation and drug release.