Ana C. Silva

Applications of polymeric and lipid nanoparticles in ophthalmic pharmaceutical formulations: present and future considerations.

The unique properties and characteristics of ocular tissues and the whole set of defence mechanisms of the ocular globe make the instillation of ocular drugs into a difficult task with a low rate of therapeutic response. One of the challenges for the new generation of ophthalmic pharmaceutical formulations is to increase the bioavailability of drugs administered by the ocular route and, therefore, their therapeutic efficacy. This can be achieved with the use of some strategies that provide an increase in the formulation pre-corneal residence time, mucoadhesion and penetration across the eye tissues. Colloidal carrier systems have been very successfully used for the selective and targeted delivery of drugs for several routes of administration. In this context, nanoparticles prepared with specific polymers or lipids and coated, dispersed or suspended in polymer solutions with mucoadhesion properties or in situ gelling properties will be an excellent strategy that deserves attention and further research. In this review, the characteristics and main properties of polymeric and lipid nanoparticles are discussed and examples and advantages of the application of these colloidal carrier systems for the ophthalmic administration of drugs are presented. The future directions of the research required in this specific field are also presented.

Design, characterization, and clinical evaluation of argan oil nanostructured lipid carriers to improve skin hydration.

Given its advantages in skin application (eg, hydration, antiaging, and protection), argan oil could be used in both dermatological and cosmetic formulations. Therefore, the preparation of nanostructured lipid carriers (NLCs) using argan oil as a liquid lipid is a promising technique, since the former constitute well-established systems for dermal delivery. The aim of this work was to develop a topical formulation of argan oil NLCs to improve skin hydration. Firstly an NLC dispersion was developed and characterized, and afterward an NLC-based hydrogel was prepared. The in vivo evaluation of the suitability of the prepared formulation for the proposed application was assessed in volunteers, by measuring different skin-surface parameters for 1 month. An argan oil NLC-based hydrogel formulation was successfully prepared and characterized. Moreover, the entrapment of the NLCs in the hydrogel net did not affect their colloidal sizes. Additionally, it was observed that this formulation precipitated an increase in skin hydration of healthy volunteers. Therefore, we concluded that the preparation of NLC systems using argan oil as the liquid lipid is a promising strategy, since a synergistic effect on the skin hydration was obtained (ie, NLC occlusion plus argan oil hydration).

Lipid Nanoparticles for the Delivery of Biopharmaceuticals

Biopharmaceuticals comprise therapeutic protein-based, nucleic acids and cell-based products. According to their therapeutic success, the clinical use of these products has been growing. Therefore, the development of efficient biopharmaceuticals delivery systems, which overcome their limitations for administration, remains an excellent prospect for pharmaceutical technologists. In this area, lipid nanoparticles have been increasingly recognized as one of the most promising delivery systems, due to their exclusive advantages. However, no clinical biopharmaceutical lipid nanoparticle-based products are yet available. This fact could be explained by the lack or failure of in vivo studies, regarding stability and toxicological concerns, and also by the complex regulatory issues that must be accomplished. The present review article focuses on the different classes of biopharmaceuticals, their characteristics and limitations for administration. A state of the art regarding the use of lipid nanoparticles to improve biopharmaceuticals delivery is presented and a critical prospect of the future directions that should be addressed by pharmaceutical technologists is also discussed.

Delivery systems for biopharmaceuticals. Part II: Liposomes, Micelles, Microemulsions and Dendrimers

Biopharmaceuticals are a generation of drugs that include peptides, proteins, nucleic acids and cell products. According to their particular molecular characteristics (e.g. high molecular size, susceptibility to enzymatic activity), these products present some limitations for administration and usually parenteral routes are the only option. To avoid these limitations, different colloidal carriers (e.g. liposomes, micelles, microemulsions and dendrimers) have been proposed to improve biopharmaceuticals delivery. Liposomes are promising drug delivery systems, despite some limitations have been reported (e.g. in vivo failure, poor long-term stability and low transfection efficiency), and only a limited number of formulations have reached the market. Micelles and microemulsions require more studies to exclude some of the observed drawbacks and guarantee their potential for use in clinic. According to their peculiar structures, dendrimers have been showing good results for nucleic acids delivery and a great development of these systems during next years is expected. This is the Part II of two review articles, which provides the state of the art of biopharmaceuticals delivery systems. Part II deals with liposomes, micelles, microemulsions and dendrimers.

Current Progresses on Nanodelivery Systems for the Treatment of Neuropsychiatric Diseases: Alzheimer’s and Schizophrenia

Currently Alzheimers disease and schizophrenia are both well-established neuropsychiatric diseases. Nonetheless, the treatment of these disorders is not unanimous and fully effective. As a consequence, several approaches have been studied to improve patients conditions. In this context, the development of new drug nanodelivery systems to increase drug bioavailability and reduce adverse effects has been claimed as a good option. Among these systems we focus on the ones that seem to be most promising, such as lipidbased systems (e.g. liposomes, nanoemulsions and lipid nanoparticles), drug nanocrystals, polymeric nanoparticles and micelles. Moreover, the application of these systems by means of alternative administration routes is also discussed. Regardless of the satisfactory results and the associated progresses that have been done in the last years, more studies are required to quickly licence the application of drug nanodelivery systems in human medicines.

Formulations based on solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for cutaneous use: A review

ABSTRACT Cutaneous use of lipid nanoparticles (solid lipid nanoparticles, SLN and nanostructured lipid carriers, NLC) has been showing promising results. These systems consist of low viscosity aqueous dispersions, being usually employed by means of semi‐solid formulations with adequate consistency for skin application. This review addresses the cutaneous use of lipid nanoparticles for therapeutic and cosmetic applications. Initially, general information related to pharmaceutical semi‐solid formulations is presented. Afterwards, the effects of SLN and NLC on the skin, and technological aspects related to semi‐solid systems based on SLN or NLC are described. Finally, the most relevant studies related to the formulations based on SLN and NLC, for cosmetic and therapeutic applications, are reported. Notwithstanding the cutaneous use of SLN and NLC has been proposed for both local and transdermal delivery, the reported studies show promising results only for local application. In this sense, more research is required to better understanding the interaction mechanisms of lipid nanoparticles with skin lipids. Furthermore, the development of standard methods for skin experiments with nanoparticles is necessary. Graphical abstract Figure. No Caption available.

Therapeutic Strategies for Alzheimer's and Parkinson's Diseases by Means of Drug Delivery Systems

Alzheimers and Parkinsons diseases are prevalent neurodegenerative disorders worldwide, which are essentially related to aging. Within the remarkable era of nanomedicine, nowadays several delivery systems have been suggested to improve the treatment of these disorders, namely, liposomes, micelles, nanoparticles (polymeric, lipid, metallic and inorganic), exosomes, dendrimers and fullerenes. The advantage that has been claimed to these delivery systems is that they facilitate the passage of drugs through the blood brain barrier (BBB), enabling targeting before body degradation, and increasing therapeutic efficacy, comparied to conventional pharmaceutical dosage forms. This review article provides a state of the art regarding the drug delivery systems that have been studied for the treatment of Alzheimers and Parkinsons diseases. It begins with a brief description of the central nervous system (CNS) and the mechanisms involved in the development of these diseases. Later, some examples of drugs used in the treatment of these neurodegenerative diseases are presented, which are currently available in conventional pharmaceutical dosage forms, and in new drug delivery systems that are under development.

Lipid Nanoparticles for Nasal/Intranasal Drug Delivery

Studies on the development of drug delivery systems have increased because these systems have particular characteristics that allow them to improve therapeutics. Among these, lipid nanoparticles (solid lipid nanoparticles, SLNs; and nanostructured lipid carriers, NLCs) have demonstrated suitability for drug targeting. The nasal administration of drug-loaded lipid nanoparticles showed effectiveness in treating central nervous system (CNS) disorders, particularly neurodegenerative diseases, because the nasal route (also called intranasal route) allows direct nose-to-brain drug delivery by means of lipid nanoparticles. Nonetheless, the feasibility of this application remains an open field for researchers. Drawbacks must be overcome before reaching the clinic (e.g., drug absorption at subtherapeutic levels, rapid mucociliary clearance). The intranasal administration of drugs for systemic absorption is effective for treating other conditions, such as cardiovascular diseases, infections, severe pain, and menopausal syndrome. In the near future, it is expected that patients will benefit from the advantages of lipid nanoparticle-based formulations, via the nasal/intranasal route, which bypasses the blood-brain barrier (BBB), avoiding first-pass metabolism and gastrointestinal degradation. This review discusses the use of SLNs and NLCs for nasal drug administration. A brief description of the nasal route and the features of SLNs and NLCs is initially provided.

Characterization and biocompatibility evaluation of cutaneous formulations containing lipid nanoparticles

Nanostructured lipid carriers (NLC) are well-known systems that show effectiveness to improve skin hydration, being suggested for cosmetic and dermatological use. Nonetheless, NLC dispersions present low viscosity, which is non-attractive for cutaneous application. To circumvent this drawback, the dispersions can be gelled or incorporated in semisolid systems, increasing the final formulation consistency. In this study, we prepared a hydrogel based on NLC containing vitamin E (HG-NLCVE) and evaluated its suitability for cutaneous application. The experiments started with the HG-NLCVE characterization (organoleptic analysis, accelerated stability, particle size, morphology, pH, texture and rheology). Afterwards, in vitro experiments were carried out, evaluating the formulation biocompatibility (MTT and Neutral Red) and irritant potential (Hens egg test on the chorioallantoic membrane, HET-CAM) for cutaneous application. The results showed that the HG-NLCVE has adequate features for skin application, is biocompatible and non-irritant. From this study, it was predicted the in vivo irritant potential of the developed formulation, avoiding the need to perform a high number of tests on human volunteers. Regarding vitamin E and NLC potential to improve skin hydration, we suggest that the HG-NLCVE could be used in cosmetic (e.g. moisturizers and anti-aging) or dermatologic (e.g. xerosis and other skin disorders) products.

Biosimilar medicines used for cancer therapy in Europe: a review

This article provides an updated review of the biosimilar medicines approved for cancer therapy in the European Union (EU). First we discuss the most relevant aspects for the development and approval of biosimilar medicines. We then present the oncological biosimilar drugs currently used, which include epoetins (alpha and zeta), filgrastim, and monoclonal antibodies (rituximab, trastuzumab and bevacizumab). Among the clinical applications of biosimilar medicines, cancer therapy remains the main target area and more approved biosimilars are expected over the next few years, providing cost-effective drugs to more patients. Furthermore, comprehensive pharmacovigilance studies are going on, monitoring the marketed biosimilars, and providing more feasible information to clinicians regarding the safety and efficacy of these medications.