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.     

A review on nanoparticle-based technologies for biodetoxification

Nanotechnology has gained significant penetration to different fields of medicine including drug delivery, disease interrogation, targeting and bio-imaging. In recent years, efforts have been put forth to assess the use of this technology in biodetoxification. In this review, we will discuss the current status of nanostructured biomaterials/nanoparticle (NP)-based technologies as a candidate biodetoxifying agent. Patient hospitalization due to illicit drug consumption, suicidal attempts and accidental toxin exposure are major challenges in the medical field. Overdoses of drugs/toxic chemicals or exposure to bacterial toxins or poisons are conventionally treated by voiding the stomach, administering activated charcoal or by using specific antidotes, if the toxin is known. Because of the limitations of these methods for safe and effective detoxification, advancements in nanotechnology may offer novel ways in intoxication support by using nanostructured biomaterials, such as liposomes, micellar nanocarriers, liquid crystalline nanoassemblies and ligand-based NPs.     

Core–shell nanocarriers for cancer therapy. Part I: biologically oriented design rules

Introduction: The application of nanotechnologies to the cancer field for therapeutic, imaging or diagnostic purposes represents an advanced and very attractive approach to overcome the main limits related to conventional chemotherapy. In particular, core–shell nanocarriers can be engineered to provide adequate features to overcome the main biological barriers encountered by free anti-cancer drugs.

Areas covered: This review will try to summarise the design rules – as dictated by biological requirements – to take into account for proper nanocarrier design and to highlight the potential of administration routes other than intravenous.

Expert opinion: Although intravenous injection remains the most investigated route of administration for ‘nanoncologicals', research interest towards less explored administration routes allowing localised chemotherapy or delivery in close proximity to the tumour site might change the way cancer is treated in the near future. Nevertheless, an experimental set-up more biologically oriented taking into account an in-depth evaluation of stability in complex media, protein interaction, and cell interaction of novel nanoconstructs could allow their successful translation in pre-clinical and clinical settings.     

Recent Advances in Platinum (IV) Complex‐Based Delivery Systems to Improve Platinum (II) Anticancer Therapy

Cisplatin and its platinum (Pt) (II) derivatives play a key role in the fight against various human cancers such as testicular, ovarian, head and neck, lung tumors. However, their application in clinic is limited due to dose‐ dependent toxicities and acquired drug resistances, which have prompted extensive research effort toward the development of more effective Pt (II) delivery strategies. The synthesis of Pt (IV) complex is one such an area of intense research fields, which involves their in vivo conversion into active Pt (II) molecules under the reducing intracellular environment, and has demonstrated encouraging preclinical and clinical outcomes. Compared with Pt (II) complexes, Pt (IV) complexes not only exhibit an increased stability and reduced side effects, but also facilitate the intravenous‐to‐oral switch in cancer chemotherapy. The overview briefly analyzes statuses of Pt (II) complex that are in clinical use, and then focuses on the development of Pt (IV) complexes. Finally, recent advances in Pt (IV) complexes in combination with nanocarriers are highlighted, addressing the shortcomings of Pt (IV) complexes, such as their instability in blood and irreversibly binding to plasma proteins and nonspecific distribution, and taking advantage of passive and active targeting effect to improve Pt (II) anticancer therapy.     

Polymeric micelle nanocarriers for targeted epidermal delivery of the hedgehog pathway inhibitor vismodegib: formulation development and cutaneous biodistribution in human skin

Background: The aim was to investigate cutaneous delivery and biodistribution of the hedgehog pathway inhibitor, vismodegib (VSD), indicated for basal cell carcinoma (BCC), from polymeric micelle formulations under infinite/finite dose conditions.

Methods: VSD-loaded micelles were characterized for drug content, particle size, and shape; a micelle gel was characterized for its rheological behavior. Cutaneous deposition and biodistribution of VSD were determined using porcine and human skin in vitro with quantification by UHPLC-MS/MS.

Results: The optimal micelle solution (Z_av 20–30 nm) increased the aqueous solubility of VSD by >8000-fold; drug content was stable after 4 weeks at 4°C. Application of micelle solution and micelle gel (0.086% w/v) to human skin for 12 h under infinite dose conditions resulted in statistically equivalent VSD deposition (0.62 ± 0.11 and 0.67 ± 0.14 μg/cm², respectively). Cutaneous biodistribution in human skin under infinite (micelle solution and gel) and finite (micelle gel) dose conditions showed that the VSD concentrations obtained in the basal epidermis, at depths of 120–200 μm, were ?3800- and ?2300-fold greater than the IC₅₀ reported for hedgehog signaling pathway inhibition in vitro.

Conclusion: Cutaneous delivery of VSD from micelle-based formulations might enable targeted, topical treatment of superficial BCC with minimal risk of systemic exposure.     

Peptides as a therapeutic avenue for nanocarrier-aided targeting of glioma

Introduction: Very few successful interventions have been possible in glioma therapy owing to its aggressive nature as well as its hindrance of targeted therapy together with the limited access afforded by the blood–brain barrier (BBB). With the advent of nanotechnology based delivery vehicles such as micelles, dendrimers, polymer-based nanoparticles and nanogels, the breach of the BBB has been facilitated. However, there remains the issue of targeted therapy for glioma cells. Peptide-mediated surface modification of nanocarriers serves this purpose, extending the ability to target glioma further than the enhanced permeability and retention effect.

Areas covered: Here we have tried to re-establish the significance of peptides that could be used in various ways for treating glioma. Peptide-embellished nanocarriers used to deliver anticancer drugs; nucleic acids (siRNA, miRNA); micelles or dendrimers grafted with immunogenic glioma-derived peptides used for stimulating active immunity in vaccine therapy, glioma targets for cell penetrating peptides and homing to specific receptors are reviewed.

Expert opinion: Peptides have multifunctional potential in targeting, BBB and cell penetration, and can serve as antagonists of various ligands and agonists of particular over-expressed receptors as discussed in this review. Using peptides in targeted personalized therapy would be one step forward and may offer new avenues for glioma therapeutics.     

口服结肠靶向纳米载体的研究进展

通过对近年来有关口服结肠靶向给药纳米载体的文献进行归纳和总结,列出了常用的新型口服结肠靶向纳米给药载体如纳米粒、纳米乳、胶束、脂质体纳米凝胶和纳米混悬液等。结肠靶向纳米载体可使药物选择性到达结肠部位,减少给药剂量、降低药物毒副作用,从而提高药物口服生物利用度,发挥治疗结肠相关疾病的作用。     

Solid lipid nanocarriers in drug delivery: characterization and design

Introduction: Solid lipid nanoparticles are promising drug carriers for systemic circulations as well as local applications. One of the major challenges for drug delivery is designing nanocarriers for efficient delivery of active substances to the target site and facilitating drug absorption.

Areas covered: In this article, the effects of excipients and particle preparation methods on the properties of solid lipid nanocarriers (SLNCs) and their impact on drug absorption and efficacies related to different administration routes are reviewed and discussed.

Expert opinion: SLNCs have special characteristics, making them attractive as drug delivery systems, for parenteral and oral delivery for systemic effects, or ocular, pulmonary and topical delivery to enhance local treatment efficacy and reducing systemic side effects. Both excipients and fabrication methods are crucial for the function and size of nanoparticles and should be considered simultaneously in designing particles to obtain the optimal drug absorption and efficacy, especially for local treatments. Despite the demonstrated advantages by the preclinical studies, further studies on improved understanding of the interactions of SLNCs with biological tissues of the target site is necessary for efficient designing functional nanoparticles for clinical applications.

Abbreviations: DG: diglycerides; FFA: free fatty acids; GMS: glyceryl monostearate; MG: monoglycerides; NLC: nanostructured lipid carriers; PL: phospholipids; SLM: solid lipid microparticles; SLN: solid lipid nanoparticles; SLNC: solid lipid nanocarriers; TG: triglycerides.