Nanomedicines: From Bench to Bedside and Beyond

Advancing nanomedicines from concept to clinic requires integration of new science with traditional pharmaceutical development. The medical and commercial success of nanomedicines is greatly facilitated when those charged with developing nanomedicines are cognizant of the unique opportunities and technical challenges that these products present. These individuals must also be knowledgeable about the processes of clinical and product development, including regulatory considerations, to maximize the odds for successful product registration. This article outlines these topics with a goal to accelerate the combination of academic innovation with collaborative industrial scientists who understand pharmaceutical development and regulatory approval requirements—only together can they realize the full potential of nanomedicines for patients.     

Assessment of efficacy of dendritic cell therapy and viral therapy in high grade glioma clinical trials. A meta-analytic review

ABSTRACT

In recent years, immunotherapy has raised the interest of many studies and provided different perspectives for the therapeutic management of high grade glioma. Our meta-analysis focused on the effectiveness of dendritic cell (DC) therapy and viral therapy (VT) in clinical trials. Fourteen eligible studies have been evaluated and the results suggest the improvement of both OS (HR = 0.65) (p < 0.0001) and PFS (HR = 0.59) (p = 0.01) for patients receiving DC therapy. The data for VT showed a slight improvement in terms of OS (HR = 0.81), while PFS was similar to the control arms (HR = 1.06) (p = 0.41).     

Decreased Mechanical Strength and Collagen Content in SPARC‐Null Periodontal Ligament Is Reversed by Inhibition of Transglutaminase Activity

The periodontal ligament (PDL) is a critical tissue that provides a physical link between the mineralized outer layer of the tooth and the alveolar bone. The PDL is composed primarily of nonmineralized fibrillar collagens. Expression of secreted protein acidic and rich in cysteine (SPARC/osteonectin), a collagen‐binding matricellular protein, has been shown to be essential for collagen homeostasis in PDL. In the absence of SPARC, PDL collagen fibers are smaller and less dense than fibers that constitute WT PDL. The aim of this study was to identify cellular mechanisms by which SPARC affected collagen fiber assembly and morphology in PDL. Cross‐linking of fibrillar collagens is one parameter that is known to affect insoluble collagen incorporation and fiber morphology. Herein, the reduction in collagen fiber size and quantity in the absence of SPARC expression was shown to result in a PDL with reduced molar extraction force in comparison to that of WT mice (C57Bl/6J). Furthermore, an increase in transglutaminase activity was found in SPARC‐null PDL by biochemical analyses that was supported by immunohistochemical results. Specifically, collagen I was identified as a substrate for transglutaminase in PDL and transglutaminase activity on collagen I was found to be greater in SPARC‐null tissues in comparison to WT. Strikingly, inhibition of transglutaminase activity in SPARC‐null PDL resulted in increases in both collagen fiber thickness and in collagen content, whereas transglutaminase inhibitors injected into WT mice resulted in increases in collagen fiber thickness only. Furthermore, PDL treated with transglutaminase inhibitors exhibited increases in molar extraction force in WT and in SPARC‐null mice. Thus, SPARC is proposed to act as a critical regulator of transglutaminase activity on collagen I with implications for mechanical strength of tissues. © 2015 American Society for Bone and Mineral Research     

Nanoparticles and Nanostructured Surface Fabrication for Innovative Cranial and Maxillofacial Surgery

A novel strategy to improve the success of soft and hard tissue integration of titanium implants is the use of nanoparticles coatings made from basically any type of biocompatible substance, which can advantageously enhance the properties of the material, as compared to its similar bulk material. So, most of the physical methods approaches involve the compaction of nanoparticles versus micron-level particles to yield surfaces with nanoscale grain boundaries, simultaneously preserving the chemistry of the surface among different topographies. At the same time, nanoparticles have been known as one of the most effective antibacterial agents and can be used as effective growth inhibitors of various microorganisms as an alternative to antibiotics. In this paper, based on literature research, we present a comprehensive review of the mechanical, physical, and chemical methods for creating nano-structured titanium surfaces along with the main nanoparticles used for the surface modification of titanium implants, the fabrication methods, their main features, and the purpose of use. We also present two patented solutions which involve nanoparticles to be used in cranioplasty, i.e., a cranial endoprosthesis with a sliding system to repair the traumatic defects of the skull, and a cranial implant based on titanium mesh with osteointegrating structures and functional nanoparticles. The main outcomes of the patented solutions are: (a) a novel geometry of the implant that allow both flexible adaptation of the implant to the specific anatomy of the patient and the promotion of regeneration of the bone tissue; (b) porous structure and favorable geometry for the absorption of impregnated active substances and cells proliferation; (c) the new implant model fit 100% on the structure of the cranial defect without inducing mechanical stress; (d) allows all kinds of radiological examinations and rapid osteointegration, along with the patient recover in a shorter time.     

Is there a reason for concern or is it just hype? – A systematic literature review of the clinical consequences of switching from originator biologics to biosimilars

Introduction: While prescribing biosimilars to patients naive to a biologic treatment is a well-accepted practice, switching clinically stable patients from an originator to a biosimilar is an issue for clinicians. Well-designed clinical trials and real-world data which study the consequences of switching from an originator biologic treatment to its biosimilar alternative are limited, especially for monoclonal antibodies.

Areas covered: A systematic literature review was conducted on PubMed to identify evidence of the consequences of switching from original biologics to biosimilars. References of included papers were also scrutinized. After a title-, abstract- and full text screening, out of the 153 original hits and 77 additional ones from screening the references, 58 papers (12 empirical papers, 5 systematic reviews and 41 non-empirical papers) were included.

Expert opinion: Preventing patients on biologic medicines from switching to biosimilars due to anticipated risks seems to be disproportional compared to the expected cost savings and/or improved patient access. Indeed, it is the opinion of the authors that the concern of switching to biosimilars is overhyped.     

Acute complications after laparoscopic bariatric procedures: update for the general surgeon

Background

Development and widespread use of laparoscopic bariatric surgery exposes emergency room physicians and general surgeons to face acute or chronic surgical complications of bariatric surgery.

Methods

The most common surgical emergencies after bariatric surgery are examined based on an extensive review of bariatric surgery literature and on the personal experience of the authors' practice in four high-volume bariatric surgery centers.

Results

An orderly stepwise approach to the bariatric patient with an emergency condition is advisable. Resuscitation should follow the same protocol adopted for the non-bariatric patients. Consultation with the bariatric surgeon should be obtained early, and referral to the bariatric center should be considered whenever possible. The identification of the surgical procedure to which the patient was submitted will orient in the diagnosis of the acute condition. Procedure-specific complication should always be taken into consideration in the differential diagnosis. Acute slippage is the most frequent complication that needs emergency treatment in a laparoscopic gastric banding. Sleeve gastrectomy and gastric bypasses may present with life-threatening suture leaks or suture line bleeding. Gastric greater curvature plication (investigational restrictive procedure) can present early complications related to prolonged postoperative vomiting. Both gastric bypass and bilio-pancreatic diversion may cause anastomotic marginal ulcer, bleeding, or rarely perforation and severe stenosis, while small bowel obstruction due to internal hernia represents a surgical emergency, also caused by trocar site hernia, intussusceptions, adhesions, strictures, kinking, or blood clots. Rapid weight loss after bariatric surgery can cause cholecystitis or choledocholithiasis, which are difficult to treat after bypass procedures.

Conclusions

The general surgeon should be informed about modern bariatric procedures, their potential acute complications, and emergency management.