Local antimicrobial delivery systems for prophylaxis and treatment of periprosthetic traumatological infections.

Infections associated with implants are the most serious complications in joint replacement surgeries and can jeopardize the functionality of orthopedic implants. Local antimicrobial delivery could enable antibiotics to attain concentrations above the minimum inhibitory concentration (MIC) threshold at the joint replacement site while preventing systemic side effects. Therefore, there is a dire need for the development of improved biomaterial-based delivery systems for local antibiotic administration in prosthetic infections.

Development and characterization of lipid nanocapsules loaded with iron oxide nanoparticles for magnetic targeting to the blood-brain barrier.

Brain drug delivery is severely hindered by the presence of the blood-brain barrier (BBB). Its functionality relies on the interactions of the brain endothelial cells with additional cellular constituents, including pericytes, astrocytes, neurons, or microglia. To boost brain drug delivery, nanomedicines have been designed to exploit distinct delivery strategies, including magnetically driven nanocarriers as a form of external physical targeting to the BBB.

Cyclosporin A-loaded dissolving microneedles for dermatitis therapy: Development, characterisation and efficacy in a delayed-type hypersensitivity in vivo model.

Several drugs can be used for treating inflammatory skin pathologies like dermatitis and psoriasis. However, for the management of chronic and long-term cases, topical administration is preferred over oral delivery since it prevents certain issues due to systemic side effects from occurring. Cyclosporin A (CsA) has been used for this purpose; however, its high molecular weight (1202 Da) restricts the diffusion through the skin structure.

Latest advances in glucose-responsive microneedle-based systems for transdermal insulin delivery.

The development of a self-regulated minimally invasive system for insulin delivery can be considered as the holy grail in the field of diabetes mellitus. A delivery system capable of releasing insulin in response to blood glucose levels would significantly improve the quality of life of diabetic patients, eliminating the need for frequent finger-prick tests and providing better glycaemic control with lower risk of hypoglycaemia. In this context, the latest advances in glucose-responsive microneedle-based transdermal insulin delivery are here compiled with a thorough analysis of the delivery mechanisms and challenges lying ahead in their clinical translation.

Antibiotic resistance and tolerance: What can drug delivery do against this global threat?

Antimicrobial resistance and tolerance (AMR&T) are urgent global health concerns, with alarmingly increasing numbers of antimicrobial drugs failing and a corresponding rise in related deaths. Several reasons for this situation can be cited, such as the misuse of traditional antibiotics, the massive use of sanitizing measures, and the overuse of antibiotics in agriculture, fisheries, and cattle. AMR&T management requires a multifaceted approach involving various strategies at different levels, such as increasing the patient's awareness of the situation and measures to reduce new resistances, reduction of current misuse or abuse, and improvement of selectivity of treatments.

Assessment of In Vitro Release Testing Methods for Colloidal Drug Carriers: The Lack of Standardized Protocols.

Although colloidal carriers have been in the pipeline for nearly four decades, standardized methods for testing their drug-release properties remain to be established in pharmacopeias. The in vitro assessment of drug release from these colloidal carriers is one of the most important parameters in the development and quality control of drug-loaded nano- and microcarriers. This lack of standardized protocols occurs due to the difficulties encountered in separating the released drug from the encapsulated one.

An overview of in vitro 3D models of the blood-brain barrier as a tool to predict the in vivo permeability of nanomedicines.

The blood-brain barrier (BBB) prevents efficient drug delivery to the central nervous system. As a result, brain diseases remain one of the greatest unmet medical needs. Understanding the tridimensional structure of the BBB helps gain insight into the pathology of the BBB and contributes to the development of novel therapies for brain diseases.

Embolization therapy with microspheres for the treatment of liver cancer: State-of-the-art of clinical translation.

Embolization with microspheres is a therapeutic strategy based on the selective occlusion of the blood vessels feeding a tumor. This procedure is intraarterially performed in the clinical setting for the treatment of liver cancer. The practice has evolved over the last decade through the incorporation of drug loading ability, biodegradability and imageability with the subsequent added functionality for the physicians and improved clinical outcomes for the patients.

Limitations and Challenges in the Stability of Cysteamine Eye Drop Compounded Formulations.

Accumulation of cystine crystals in the cornea of patients suffering from cystinosis is considered pathognomonic and can lead to severe ocular complications. Cysteamine eye drop compounded formulations, commonly prepared by hospital pharmacy services, are meant to diminish the build-up of corneal cystine crystals. The objective of this work was to analyze whether the shelf life proposed for six formulations prepared following different protocols used in hospital pharmacies is adequate to guarantee the quality and efficacy of cysteamine eye drops.

The combination of medical devices and medicinal products revisited from the new European legal framework.

Medical devices and medicinal products have many similarities in their nature, scope or specific medical purposes, and despite the differences in their principal means of action, they are often used in combination. Indeed, many medicinal products depend on medical devices for their administration, and it is increasingly common for medical devices to contain medicinal substances to support their action. Therefore, the combination of medicinal products and medical devices provides additional benefits for patients.

Timeline of Translational Formulation Technologies for Cancer Therapy: Successes, Failures, and Lessons Learned Therefrom.

Over the past few decades, the field of cancer therapy has seen a significant change in the way in which formulations are designed and developed, resulting in more efficient products that allow us to ultimately achieve improved drug bioavailability, efficacy, and safety. However, although many formulations have entered the market, many others have fallen by the wayside leaving the scientific community with several lessons to learn. The successes (and failures) achieved with formulations that have been approved in Europe and/or by the FDA for the three major types of cancer therapy (peptide-based therapy, chemotherapy, and radiotherapy) are reviewed herein, covering the period from the approval of the first prolonged-release system for hormonal therapy to the appearance of the first biodegradable microspheres intended for chemoembolization in 2020.

Glioblastoma chemotherapeutic agents used in the clinical setting and in clinical trials: Nanomedicine approaches to improve their efficacy.

Even though substantial advances in understanding glioma pathogenesis have prompted a more rational design of potential therapeutic strategies, glioblastoma multiforme remains an incurable disease with the lowest median overall survival among all malignant brain tumours. Therefore, there is a dire need to find novel drug delivery strategies to improve the current dismal survival outcomes. In this context, nanomedicine offers an appealing alternative as it shows potential to improve brain drug delivery.

Controlled Release of Highly Hydrophilic Drugs from Novel Poly(Magnesium Acrylate) Matrix Tablets.

The potential of a new poly(magnesium acrylate) hydrogel (PAMgA) as a pharmaceutical excipient for the elaboration of matrix tablets for the extended release of highly hydrophilic drugs was evaluated. The polymer was synthetized with two different crosslinking degrees that were characterized by FTIR and DSC. Their acute oral toxicity was determined in a mouse model, showing no toxicity at doses up to 10 g/kg.

Size-Tailored Design of Highly Monodisperse Lipid Nanocapsules for Drug Delivery.

The empirical development of nanocarriers has unfortunately led to high attrition rates in clinical trials. This underpins the importance of the rational design of nanomedicines to achieve efficient disease-driven therapies. Since particle size certainly influences behaviour, rational disease-driven colloid design can only be achieved by determining the parameters that accurately control their size distribution.

Cannabidiol Enhances the Passage of Lipid Nanocapsules across the Blood-Brain Barrier Both in Vitro and in Vivo.

Diseases affecting the central nervous system (CNS) should be regarded as a major health challenge due to the current lack of effective treatments given the hindrance to brain drug delivery imposed by the blood-brain barrier (BBB). Since efficient brain drug delivery should not solely rely on passive targeting, active targeting of nanomedicines into the CNS is being explored. The present study is devoted to the development of lipid nanocapsules (LNCs) decorated with nonpsychotropic cannabinoids as pioneering nonimmunogenic brain-targeting molecules and to the evaluation of their brain-targeting ability both in vitro and in vivo.

Lipid nanocapsules decorated and loaded with cannabidiol as targeted prolonged release carriers for glioma therapy: In vitro screening of critical parameters.

The therapeutic potential of cannabinoids has been truly constrained heretofore due to their strong psychoactive effects and their high lipophilicity. In this context, precisely due to the lack of psychoactive properties, cannabidiol (CBD), the second major component of Cannabis sativa, arises as the phytocannabinoid with the most auspicious therapeutic potential. Hence, the incorporation of CBD in lipid nanocapsules (LNCs) will contribute to overcome the dosing problems associated with cannabinoids.

In vitro screening of nanomedicines through the blood brain barrier: A critical review.

The blood-brain barrier accounts for the high attrition rate of the treatments of most brain disorders, which therefore remain one of the greatest health-care challenges of the twenty first century. Against this background of hindrance to brain delivery, nanomedicine takes advantage of the assembly at the nanoscale of available biomaterials to provide a delivery platform with potential to raising brain levels of either imaging or therapeutic agents. Nevertheless, to prevent later failure due to ineffective drug levels at the target site, researchers have been endeavoring to develop a battery of in vitro screening procedures that can predict earlier in the drug discovery process the ability of these cutting-edge drug delivery platforms to cross the blood-brain barrier for biomedical purposes.

Glioblastoma Multiforme and Lipid Nanocapsules: A Review.

Epidemiological data on central nervous system disorders call for a focus on the major hindrance to brain drug delivery, blood-central nervous system barriers. Otherwise, there is little chance of improving the short-term survival of patients with diseases such as glioblastoma multiforme, which is one of the brain disorders associated with many years of life lost. Targetable nanocarriers for treating malignant gliomas are a unique way to overcome low chemotherapeutic levels at target sites devoid of systemic toxicity.