Recent Advancement of Chitosan-Based Nanoparticles for Oral Controlled Delivery of Insulin and Other Therapeutic Agents

Nanoparticles composed of naturally occurring biodegradable polymers have emerged as potential carriers of various therapeutic agents for controlled drug delivery through the oral route. Chitosan, a cationic polysaccharide, is one of such biodegradable polymers, which has been extensively exploited for the preparation of nanoparticles for oral controlled delivery of several therapeutic agents. In recent years, the area of focus has shifted from chitosan to chitosan derivatized polymers for the preparation of oral nanoparticles due to its vastly improved properties, such as better drug retention capability, improved permeation, enhanced mucoadhesion and sustained release of therapeutic agents. Chitosan derivatized polymers are primarily the quaternized chitosan derivatives, chitosan cyclodextrin complexes, thiolated chitosan, pegylated chitosan and chitosan combined with other peptides. The current review focuses on the recent advancements in the field of oral controlled release via chitosan nanoparticles and discusses about its in vitro and in vivo implications.     

In silico Structure Modeling and Comparative Analysis of Characterization Properties of Protein Polymers Useful for Protein-Based Nano Particulate Drug Delivery Systems (NPDDS): A Bioinformatics Approach

With an increasing interest in nanoparticulate delivery systems, there is a greater need to identify biomaterials that are biocompatible and safe for human applications. Protein polymers from animal and plant sources are promising materials for designing nanocarriers. Composition of the protein plays an important role for specific drug delivery applications such as drug release, targeting, and stimuli responsive drug release. An important issue in protein polymers is characteristics such as size, charge, and hydrophobicity may play a significant role in phagocytic uptake and initiating a subsequent immune response. This remains to be investigated systematically by analyzing factors that influence nanoparticle characteristics of protein and reduce phagocytic uptake and does not initiate immune response too. Although protein polymers are biodegradable, it is essential to ensure that there must not be premature enzymatic breakdown of the protein nanoparticles in the systemic circulation. Surface modification of the protein nanoparticles can be used to address this issue to propose the necessary modification in the surface of the protein would be great contribution in the nano particulate drug delivery systems (NPPDS). Of the various proteins, gelatin and albumin have been widely studied for drug delivery applications. Plant proteins are yet to be investigated widely for drug delivery applications so there is need to find out the plant proteins capable to act as nanoparticles. The commercial success of albumin-based nanoparticles has created an interest in other proteins. An increased understanding of the physicochemical properties coupled with the developments in rDNA technology will open up new opportunities for protein-based nanoparticulate systems. In the present studies several proteins currently useful for drug delivery system were structurally modeled and has been analyzed to propose the essential characteristics of protein for protein-based NPDDS.     

Beyond traditional therapy: Mucoadhesive polymers as a new frontier in oral cancer management

In recent times mucoadhesive drug delivery systems are gaining popularity in oral cancer. It is a malignancy with high global prevalence. Despite significant advances in cancer therapeutics, improving the prognosis of late-stage oral cancer remains challenging. Targeted therapy using mucoadhesive polymers can improve oral cancer patients' overall outcome by offering enhanced oral mucosa bioavailability, better drug distribution and tissue targeting, and minimizing systemic side effects. Mucoadhesive polymers can also be delivered via different formulations such as tablets, films, patches, gels, and nanoparticles. These polymers can deliver an array of medicines, making them an adaptable drug delivery approach. Drug delivery techniques based on these mucoadhesive polymers are gaining traction and have immense potential as a prospective treatment for late-stage oral cancer. This review examines leading research in mucoadhesive polymers and discusses their potential applications in treating oral cancer.     

Biopolymer nanoparticle production for controlled release of biopharmaceuticals

Abstract

For drug applications, nanoparticles, used as drug carriers, offer the advantage of controlled release, therapeutic impact and targeted delivery. In drug delivery applications, biodegradable polymers can be extracted from natural sources or prepared synthetically by polymerization. Natural polymers typically have varying compositions and physiochemical properties. As a result, methods which utilize natural polymers to encapsulate drugs are more varied and polymer dependent. The following polymers are discussed in this review article: alginate, chitosan, gelatin, albumin, gliadin, pullulan, and dextran. Specialized encapsulation nanotechnologies will be discussed such as ionotropic gelation, complexation, the reverse microemulsion technique, cross-linking methods, emulsion-dependent methods, desolvation methods and self-assembly methods. For each biopolymer an overview of the structure is presented with the corresponding encapsulation techniques. Understanding the structure of the biopolymer is important as to not only understand the rational for current encapsulation techniques but to continue to develop new encapsulation techniques in pursuit of the ideal drug carrier for application in therapeutic treatments.     

Water-based nanoparticulate polymeric system for protein delivery

This article features a new production technology for nanoparticles comprised of multicomponent polymeric complexes that are candidates for delivery vehicles of biological molecules such as proteins and drugs. Biocompatible and mostly natural polymers are fabricated into thermodynamically stable nanoparticles insoluble in water and buffered media, in the absence of organic solvents, using two types of processing: batch and continuous. Careful choice of construction materials and the superposition of several interacting principles during their production allow for the customization of the physicochemical properties of the structures. Detailed experiments in batch and continuous systems allowed time-dependent stoichiometric characterization of the production process and an understanding of fundamental assembly principles of such supramolecular structures. Continuous-flow production is shown to provide more consistent data in terms of product quality and consistency, with further possibility of process development and commercialization. The development of nanoparticles using the described methodology is expected to lead to a flexible nanoparticle drug delivery system for medical applications, which has particular bearing to the slow release of drugs, antigens (for vaccine design), and genes (for gene therapy). Several chemistries of particles are presented. Copyright John Wiley & Sons, Inc.     

Engineered nanoparticles as precise drug delivery systems

With the remarkable development of nanotechnology in recent years, new drug delivery approaches based on the state-of-the-art nanotechnology have been receiving significant attention. Nanoparticles, an evolvement of nanotechnology, are increasingly considered as a potential candidate to carry therapeutic agents safely into a targeted compartment in an organ, particular tissue or cell. These particles are colloidal structures with a diameter smaller than 1,000 nm, and therefore can penetrate through diminutive capillaries into the cell's internal machinery. This innovative delivery technique might be a promising technology to meet the current challenges in drug delivery. When loaded with a gene or drug agent, nanoparticles can become nanopills, which can effectively treat problematical diseases such as cancer. This article summarizes different types of nanoparticles drug delivery systems under investigation and their prospective therapeutic applications. Also, this article presents a closer look at the advances, current challenges, and future direction of nanoparticles drug delivery systems.     

Cyclodextrins in drug delivery: An updated review

The purpose of this review is to discuss and summarize some of the interesting findings and applications of cyclodextrins (CDs) and their derivatives in different areas of drug delivery, particularly in protein and peptide drug delivery and gene delivery. The article highlights important CD applications in the design of various novel delivery systems like liposomes, microspheres, microcapsules, and nanoparticles. In addition to their well-known effects on drug solubility and dissolution, bioavailability, safety, and stability, their use as excipients in drug formulation are also discussed in this article. The article also focuses on various factors influencing inclusion complex formation because an understanding of the same is necessary for proper handling of these versatile materials. Some important considerations in selecting CDs in drug formulation such as their commercial availability, regulatory status, and patent status are also summarized. CDs, because of their continuing ability to find several novel applications in drug delivery, are expected to solve many problems associated with the delivery of different novel drugs through different delivery routes. Published: October 14, 2005     

Development of pH-sensitive Insulin Nanoparticles using Eudragit L100-55 and Chitosan with Different Molecular Weights

Insulin is a polypeptide hormone and usually administered for treatment of diabetic patients subcutaneously. The aim of this study was to investigate the efficiency of enteric nanoparticles for oral delivery of insulin. Nanoparticles were formed by complex coacervation method using chitosan of various molecular weights. Nanoparticles were characterized by drug loading efficiency determination, particle size analysis, Scanning Electron Microscopy (SEM), Zeta potential and CD spectroscopy (Circular Dichrosim). The in vitro release studies were performed at pH 1.2 and 7.4. The drug loaded nanoparticles showed 3.38% of entrapment, loading efficiency of 30.56% and mean particle size of 199 nm. SEM studies showed that the nanoparticles are non-spherical. Zeta potential increased with increasing molecular weight of chitosan. The CD spectroscopy profiles indicated that the nano-encapsulation process did not significantly disrupt the internal structure of insulin; additionally, pH-sensitivity of nanoparticles was preserved and the insulin release was pH-dependent. These results suggest that the complex coacervation process using chitosan and Eudragit L100-55 polymers may provide a useful approach for entrapment of hydrophilic polypeptides without affecting their conformation.     

Nanoparticles incorporated in bilaminated films: a smart drug delivery system for oral formulations

A novel smart drug delivery system (NP-Film) consisting of carboxylation chitosan-grafted nanoparticles (CCGNs) and bilaminated films, which were composed of the mucoadhesive chitosan-ethylenediaminetetraacetic acid hydrogel layer and the hydrophobic ethylcellulose layer, was developed for oral delivery of protein drugs. NP-Film was characterized by electron microscopy and fluorescence microscopy, and the results showed that the solid, spherical nanoparticles dispersed evenly in the porous structures of films. The properties of nanoparticles and films were investigated. The mucoadhesive force, CCGNs released from the NP-Film, and the toxicity of NP-Film were also evaluated. Results showed that the nanoparticles could reversibly open the tight junction of the intestine and inhibit trypsin activity. The release behavior of the nanoparticles from the NP-Film exhibited pH sensitivity. The drug delivery system possessed high mucoadhesive force and low intestinal toxicity. Therefore, the NP-Film would be a promising delivery carrier for protein drugs via oral administration.     

Drug delivery and nanoparticles:applications and hazards

The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed.     

Chitosan and lactic acid-grafted chitosan nanoparticles as carriers for prolonged drug delivery

Nanoparticles of approximately 10nm in diameter made with chitosan or lactic acid-grafted chitosan were developed for high drug loading and prolonged drug release. A drug encapsulation efficiency of 92% and a release rate of 28% from chitosan nanoparticles over a 4-week period were demonstrated with bovine serum protein. To further increase drug encapsulation, prolong drug release, and increase chitosan solubility in solution of neutral pH, chitosan was modified with lactic acid by grafting D,L-lactic acid onto amino groups in chitosan without using a catalyst. The lactic acid-grafted chitosan nanoparticles demonstrated a drug encapsulation efficiency of 96% and a protein release rate of 15% over 4 weeks. With increased protein concentration, the drug encapsulation efficiency decreased and drug release rate increased. Unlike chitosan, which is generally soluble only in acid solution, the chitosan modified with lactic acid can be prepared from solutions of neutral pH, offering an additional advantage of allowing proteins or drugs to be uniformly incorporated in the matrix structure with minimal or no denaturization.     

生物相容透皮给药微针治疗浅表肿瘤

复杂的肿瘤微环境导致抗肿瘤药物在肿瘤组织内递送效率低下，严重阻碍了药物对浅表肿瘤的治疗效果。生物相容透皮给药微针凭借较高的机械强度，刺穿皮肤角质层，将微针内的药物递送至浅表肿瘤组织内，提高生物利用度，改善静脉注射、口服给药的肝肾毒性等问题。本文介绍了生物相容透皮给药微针的设计及其在癌症化疗、光动力治疗、光热治疗、免疫治疗、基因治疗等领域的研究进展，对浅表肿瘤的微创、局部递药和精准、高效治疗具有重要指导意义。     

Nanoparticles in modern medicine: state of the art and future challenges

Nanoparticles are materials with overall dimensions in the nanoscale, ie, under 100 nm. In recent years, these materials have emerged as important players in modem medicine, with clinical applications ranging from contrast agents in imaging to carriers for drug and gene delivery into tumors. Indeed, there are some instances where nanoparticles enable analyses and therapies that simply cannot be performed otherwise. However, nanoparticles also bring with them unique environmental and societal challenges, particularly in regard to toxicity. This review aims to highlight the major contributions of nanoparticles to modem medicine and also discuss environmental and societal aspects of their use.     

纳米粒子在肿瘤干细胞治疗方面的研究进展

癌症是严重威胁人类生命健康的常见疾病之一。肿瘤细胞中存在一小部分细胞,它们具有自我更新能力,增殖分化潜能,还具有很强的成瘤能力和耐受化疗、放疗的特性,它们被称之为肿瘤干细胞。肿瘤干细胞被认为是肿瘤发生、耐药性和术后复发的根源。因此消灭肿瘤干细胞是治愈肿瘤的关键。针对肿瘤干细胞治疗的纳米药物逐渐引起人们的重视,它们具有可控缓释、靶向、生物相容性高等优点,特别是在纳米药物载体和纳米基因载体方面已经取得了显著的研究成果。然而,这些纳米药物在体内的靶向效率、稳定性、代谢途径和毒性等还需要系统的考察和检验,为其在临床上的应用打下良好的基础。本文主要综述了纳米粒子在肿瘤干细胞治疗方面的应用研究,并对纳米粒子在肿瘤干细胞治疗中存在的问题和未来的研究方向进行了展望。     

PLGA Nanoparticles as Subconjunctival Injection for Management of Glaucoma

Nanoparticles fabricated from the biodegradable and biocompatible polymer, polylactic-co-glycolic acid (PLGA), could be a promising system for targeting ocular drug delivery. The objective of this work was to investigate the possibility of encapsulating brinzolamide in PLGA nanoparticles in order to be applied as a subconjunctival injection that could represent a starting point for developing new therapeutic strategies against increase in ocular pressure. The brinzolamide-loaded PLGA nanoparticles were fabricated using emulsion-diffusion-evaporation method with varying concentrations of Tween 80 or poloxamer 188 (Plx) in aqueous and organic phases. The nanoparticles were characterized in terms of particle size and size distribution, entrapment efficiency and in-vitro drug release pattern as well as DSC and X-ray analysis. Nanoparticles prepared using Tween 80 in the aqueous phase showed higher encapsulation efficiency and smaller particle size-values compared to those prepared using Plx. Furthermore, the addition of Plx 188 or Brij 97 to the organic phase in the formulation containing Tween 80 in the aqueous phase led to an increase in the particle diameter-values of the obtained nanoparticles. The nanoparticles had the capacity to release the brinzolamide in a biphasic release profile. The nanoparticles were spherical in shape and the drug was entraped in the nanoparticles in an amorphous form. Selected nanoparticles, injected subconjunctivally in normotensive Albino rabbits, were able to reduce the IOP for up to 10 days. Nanoparticles loaded with brinzolamide with lower particle size were able to reduce the IOP for longer period compared to those with higher particle size. Histopathological studies for the anterior cross sections of the rabbits’ eyes revealed that the tested nanoparticles were compatible with the ocular tissue. The overall results support that PLGA nanoparticles, applied as subconjunctival injection, can be considered as a promising carrier for ocular brinzolamide delivery with targeting delivery of the drug to the eye tissues.     

Zwitterionic polymers in drug delivery: A review

Developments of novel drug delivery vehicles are sought-after to augment the therapeutic effectiveness of standard drugs. An urgency to design novel drug delivery vehicles that are sustainable, biocompatible, have minimized cytotoxicity, no immunogenicity, high stability, long circulation time, and are capable of averting recognition by the immune system is perceived. In this pursuit for an ideal candidate for drug delivery vehicles, zwitterionic materials have come up as fulfilling almost all these expectations. This comprehensive review is presenting the progress made by zwitterionic polymeric architectures as prospective sustainable drug delivery vehicles. Zwitterionic polymers with varied architecture such as appending protein conjugates, nanoparticles, surface coatings, liposomes, hydrogels, etc, used to fabricate drug delivery vehicles are reviewed here. A brief introduction of zwitterionic polymers and their application as reliable drug delivery vehicles, such as zwitterionic polymer–protein conjugates, zwitterionic polymer-based drug nanocarriers, and stimulus-responsive zwitterionic polymers are discussed in this discourse. The prospects shown by zwitterionic architecture suggest the tremendous potential for them in this domain. This critical review will encourage the researchers working in this area and boost the development and commercialization of such devices to benefit the healthcare fraternity.     

Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release

Magnetically-responsive nano/micro-engineered biomaterials that enable a tightly controlled, on-demand drug delivery have been developed as new types of smart soft devices for biomedical applications. Although a number of magnetically-responsive drug delivery systems have demonstrated efficacies through either in vitro proof of concept studies or in vivo preclinical applications, their use in clinical settings is still limited by their insufficient biocompatibility or biodegradability. Additionally, many of the existing platforms rely on sophisticated techniques for their fabrications. We recently demonstrated the fabrication of biodegradable, gelatin-based thermo-responsive microgel by physically entrapping poly(N-isopropylacrylamide-co-acrylamide) chains as a minor component within a three-dimensional gelatin network. In this study, we present a facile method to fabricate a biodegradable drug release platform that enables a magneto-thermally triggered drug release. This was achieved by incorporating superparamagnetic iron oxide nanoparticles and thermo-responsive polymers within gelatin-based colloidal microgels, in conjunction with an alternating magnetic field application system.     

Chitosan nanoparticles for oral drug and gene delivery

Chitosan is a widely available, mucoadhesive polymer that is able to increase cellular permeability and improve the bioavailability of orally administered protein drugs. It can also be readily formed into nanoparticles able to entrap drugs or condense plasmid DNA. Studies on the formulation and oral delivery of such chitosan nanoparticles have demonstrated their efficacy in enhancing drug uptake and promoting gene expression. This review summarizes some of these findings and highlights the potential of chitosan as a component of oral delivery systems.     

Drug and gene delivery using gold nanoparticles

Monolayer-functionalized gold nanoparticles provide attractive vehicles for pharmaceutical delivery applications as a result of their size and the unique properties and release mechanisms imparted by their monolayer. This review provides examples of recent advances in the field of drug and gene delivery using gold nanoparticles.     

Gold nanoparticles: Emerging paradigm for targeted drug delivery system

The application of nanotechnology in medicine, known as nanomedicine, has introduced a plethora of nanoparticles of variable chemistry and design considerations for cancer diagnosis and treatment. One of the most important field is the design and development of pharmaceutical drugs, based on targeted drug delivery system (TDDS). Being inspired by physio-chemical properties of nanoparticles, TDDS are designed to safely reach their targets and specifically release their cargo at the site of disease for enhanced therapeutic effects, thereby increasing the drug tissue bioavailability. Nanoparticles have the advantage of targeting cancer by simply being accumulated and entrapped in cancer cells. However, even after rapid growth of nanotechnology in nanomedicine, designing an effective targeted drug delivery system is still a challenging task. In this review, we reveal the recent advances in drug delivery approach with a particular focus on gold nanoparticles. We seek to expound on how these nanomaterials communicate in the complex environment to reach the target site, and how to design the effective TDDS for complex environments and simultaneously monitor the toxicity on the basis of designing such delivery complexes. Hence, this review will shed light on the research, opportunities and challenges for engineering nanomaterials with cancer biology and medicine to develop effective TDDS for treatment of cancer.