Hydrogels are three-dimensional polymeric systems, being able to accommodate different categories of bioactive agents and act as promising drug delivery systems in many different biomedical applications. Due to their extended 3D network, hydrogels exhibit many advantages, such as extensive loading capacity and controlled drug release profiles, combined with characteristics such as biocompatibility and biodegradability, due to their constructive polymeric biomaterials. Moreover, hydrogels are capable of being administered via different routes of administration, including systemic and topical ones, due to their tunable characteristics. Stimuli-responsive hydrogels are characterized as smart biomaterials, while environmental stimuli, such as pH, can be employed to trigger on-demand drug release from the hydrogels via the provocation of conformational changes. In the present study, an emphasis on the pH-responsive hydrogels is taking place through various literature cases in drug delivery, wound healing, and some alternative applications, including implantation, oral administration, etc., wherein many different polymeric derivatives have been utilized. Moreover, the role of each used polymer or polymeric combination with other functional biomaterials, their mode of structure formation (for example, crosslinking), and their content release mechanism are highlighted, as well as the therapeutic effect of the hydrogels on different pathological conditions, as promising candidates for pharmaceutical applications.

Lyotropic liquid crystals result from the self-assembly process of amphiphilic molecules, such as lipids, into water, being organized in different mesophases. The non-lamellar formed mesophases, such as bicontinuous cubic (cubosomes) and inverse hexagonal (hexosomes), attract great scientific interest in the field of pharmaceutical nanotechnology. In the present review, an overview of the engineering and characterization of non-lamellar lyotropic liquid crystalline nanosystems (LLCN) is provided, focusing on their advantages as drug delivery nanocarriers and innovative vaccine platforms. It is described that non-lamellar LLCN can be utilized as drug delivery nanosystems, as well as for protein, peptide, and nucleic acid delivery. They exhibit major advantages, including stimuli-responsive properties for the “on demand” drug release delivery and the ability for controlled release by manipulating their internal conformation properties and their administration by different routes. Moreover, non-lamellar LLCN exhibit unique adjuvant properties to activate the immune system, being ideal for the development of novel vaccines. This review outlines the recent advances in lipid-based liquid crystalline technology and highlights the unique features of such systems, with a hopeful scope to contribute to the rational design of future nanosystems.

Multiple sclerosis (MS) is a chronic, autoimmune, neurodegenerative disease of the central nervous system (CNS) that yields to neuronal axon damage, demyelization, and paralysis. Although several drugs were designed for the treatment of MS, with some of them being approved in the last few decades, the complete remission and the treatment of progressive forms still remain a matter of debate and a medical challenge. Nanotechnology provides a variety of promising therapeutic tools that can be applied for the treatment of MS, overcoming the barriers and the limitations of the already existing immunosuppressive and biological therapies. In the present review, we explore literature case studies on the development of drug delivery nanosystems for the targeted delivery of MS drugs in the pathological tissues of the CNS, providing high bioavailability and enhanced therapeutic efficiency, as well as nanosystems for the delivery of agents to facilitate efficient remyelination. Moreover, we present examples of tolerance-inducing nanocarriers, being used as promising vaccines for antigen-specific immunotherapy of MS. We emphasize on liposomes, as well as lipid- and polymer-based nanoparticles. Finally, we highlight the future perspectives given by the nanotechnology field toward the improvement of the current treatment of MS and its animal model, experimental autoimmune encephalomyelitis (EAE).

Poly(ethylene oxide)-poly(ε-caprolactone) (PEO-PCL) is a family of block (or graft) copolymers with several biomedical applications. These types of copolymers are well-known for their good biocompatibility and biodegradability properties, being ideal for biomedical applications and for the formation of a variety of nanosystems intended for controlled drug release. The aim of this review is to present the applications and the properties of different nanocarriers derived from PEO-PCL block and graft copolymers. Micelles, polymeric nanoparticles, drug conjugates, nanocapsules, and hybrid polymer-lipid nanoparticles, such as hybrid liposomes, are the main categories of PEO-PCL based nanocarriers loaded with different active ingredients. The advantages and the limitations in preclinical studies are also discussed in depth. PEO-PCL based nanocarriers could be the next generation of delivery systems with fast clinical translation. Finally, current challenges and future perspectives of the PEO-PCL based nanocarriers are highlighted.

There is an emerging need to evolve the conventional lyotropic liquid crystalline nanoparticles to advanced stimuli-responsive, therapeutic nanosystems with upgraded functionality. Towards this effort, typically used stabilizers, such as Pluronics^®, can be combined or replaced by smart, stimuli-responsive block copolymers. The aim of this study is to incorporate the stimuli-responsive amphiphilic block copolymer poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) (PDMAEMA-b-PLMA) as a stabilizer in lipidic liquid crystalline nanoparticles, in order to provide steric stabilization and simultaneous stimuli-responsiveness. The physicochemical and morphological characteristics of the prepared nanosystems were investigated by light scattering techniques, cryogenic-transmission electron microscopy (cryo-TEM), X-ray diffraction (XRD) and fluorescence spectroscopy. The PDMAEMA-b-PLMA, either individually or combined with Poloxamer 407, exhibited different modes of stabilization depending on the lipid used. Due to the protonation ability of PDMAEMA blocks in acidic pH, the nanoparticles exhibited high positive charge, as well as pH-responsive charge conversion, which can be exploited towards pharmaceutical applications. The ionic strength, temperature and serum proteins influenced the physicochemical behavior of the nanoparticles, while the polymer concentration differentiated their morphology; their micropolarity and microfluidity were also evaluated. The proposed liquid crystalline nanosystems can be considered as novel and attractive pH-responsive drug and gene delivery nanocarriers due to their polycationic content.

Lipid-based nanocarriers are ideal drug delivery systems for transdermal administration due to their biocompatibility and biodegradability. Their lipophilicity and/or similarity to the natural lipids of the epidermis enable intermolecular interactions with the lipid membrane and therefore result in effective passage through the skin. The purpose of this review is to focus on lipid-based drug delivery nanoplatforms administered via the transdermal route by summarizing the most recent developments with the intention of fast clinical translation. Liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), ethosomes, and transfersomes exhibit ideal physicochemical characteristics and encapsulation efficiency to enhance the effectiveness of the incorporated Active Pharmaceutical Ingredients (APIs). The state of the art for fabricating transcutaneous lipid drug delivery nanoparticles and the strategies for overcoming the current obstacles, as well as the added value of novel formulations, will be discussed within the scope of Quality by Design applications. The limitations and challenges that still exist will also be considered.