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Nanoparticle- and Nanoporous-Membrane-Mediated Delivery of Therapeutics pharmaceutics Review Nanoparticle- and Nanoporous-Membrane-Mediated Delivery of Therapeutics 1, , 2, 3 4 Mostafa Mabrouk * y , Rajakumari Rajendran y, Islam E. Soliman , Mohamed M. Ashour , Hanan H. Beherei 1, Khairy M. Tohamy 3, Sabu Thomas 2, Nandakumar Kalarikkal 2, Gangasalam Arthanareeswaran 5 and Diganta B. Das 6,* 1 Refractories, Ceramics and Building Materials Department, National Research Centre, 33 El Bohouth St (former EL Tahrirst)-Dokki, Giza 12622, Egypt; [email protected] 2 International and Inter-University Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam, Kerala 686560, India; [email protected] (R.R.); [email protected] (S.T.); [email protected] (N.K.) 3 Biophysics Branch, Faculty of Science, Al-Azhar University, Cairo 11884, Egypt; [email protected] (I.E.S.); [email protected] (K.M.T.) 4 Faculty of Engineering, Badr University, Cairo 11829, Egypt; [email protected] 5 Department of Chemical Engineering, National Institute of Technology, Tiruchirappalli 620015, India; [email protected] 6 Department of Chemical Engineering, Loughborough University, Loughborough LE113TU, UK * Correspondence: [email protected] (M.M.); [email protected] (D.B.D.); Tel.: +201097302384 (M.M.); +44-1509-222509 (D.B.D.) These authors contributed equally to this work. y Received: 1 May 2019; Accepted: 14 June 2019; Published: 21 June 2019 Abstract: Pharmaceutical particulates and membranes possess promising prospects for delivering drugs and bioactive molecules with the potential to improve drug delivery strategies like sustained and controlled release. For example, inorganic-based nanoparticles such as silica-, titanium-, zirconia-, calcium-, and carbon-based nanomaterials with dimensions smaller than 100 nm have been extensively developed for biomedical applications. Furthermore, inorganic nanoparticles possess magnetic, optical, and electrical properties, which make them suitable for various therapeutic applications including targeting, diagnosis, and drug delivery. Their properties may also be tuned by controlling different parameters, e.g., particle size, shape, surface functionalization, and interactions among them. In a similar fashion, membranes have several functions which are useful in sensing, sorting, imaging, separating, and releasing bioactive or drug molecules. Engineered membranes have been developed for their usage in controlled drug delivery devices. The latest advancement in the technology is therefore made possible to regulate the physico-chemical properties of the membrane pores, which enables the control of drug delivery. The current review aims to highlight the role of both pharmaceutical particulates and membranes over the last fifteen years based on their preparation method, size, shape, surface functionalization, and drug delivery potential. Keywords: pharmaceutical particulates; membranes; drug delivery systems; bio-imaging; bioactive molecules 1. Introduction Nanotechnology has emerged as one of the most versatile and powerful technologies in the development of drug delivery techniques. Nanomaterials include particulates which have at least one dimension of 100 nm or less. Scale differences and modification to the material surfaces result in different physico-chemical properties of the materials which make them suitable for biomedical applications Pharmaceutics 2019, 11, 294; doi:10.3390/pharmaceutics11060294 www.mdpi.com/journal/pharmaceutics Pharmaceutics 2019, 11, 294 2 of 33 such as drug delivery, disease diagnosis, and therapy. Currently, there are many applications of nanotechnology in general and nanoparticle (NP)-based drug delivery specifically. Similarly, membrane technologies that focus on both nanoporous membrane preparation and applications have developed significantly. In this context, a membrane involves a porous system which is made up of either inorganic, organic, or a combination of both inorganic and organic materials. The utilization of membranes to convey medications/bioactives is opening up new treatment preferences of interest, e.g., enhancing the Pharmaceutics 2019, 11, x FOR PEER REVIEW 2 of 33 solubility of bioactives shielding an active ingredient from corruption, enhancing the bioavailability of medication,applications lowering such lethalas drug impacts, delivery, odiseaseffering diagnosis, suitable and structures therapy. forCurrently, all courses there ofare administration, many permittingapplications advancement of nanotechnology and offering in general fitting and structures nanoparticle for (NP)-based courses drug of drugdelivery administration, specifically. and Similarly, membrane technologies that focus on both nanoporous membrane preparation and permittingapplications fast formulation have developed improvement. significantly. These In this points context, are a discussedmembrane involves further a below. porous system which is made up of either inorganic, organic, or a combination of both inorganic and organic 1.1. Why Nanoparticles?materials. The utilization of membranes to convey medications/bioactives is opening up new treatment preferences of interest, e.g., enhancing the solubility of bioactives shielding an active Thereingredient are many from diff erentcorruption, types enhancing of NPs that the bioavailability have promising of medication, biomedical lowering applications, lethal impacts, e.g., polymeric NPs, polyethyleneoffering suitable glycol structures (PEG)-ylation for all courses modified of administration, particles, permitting micelles, advancement liposomes, and dendrimers, offering and nanosizedfitting inorganic structures materials for courses [1 ].of Organicdrug administration, NPs vary and in theirpermitting activity fast formulation in different improvement. biological systems includingThese penetration points are depths discussed in further tissues below. and their toxicity and targeting efficiency [2]. Inorganic NPs regularly1.1. display Why Nanoparticles? novel physical properties as their size is close to nanometer scale measurements. For instance, the extraordinary physical and chemical properties of these NPs may prompt future There are many different types of NPs that have promising biomedical applications, e.g., applicationspolymeric in drug NPs, delivery polyethylene and biomedical glycol (PEG)-ylation imaging. Plenty modified of sophisticated particles, micelles, and di ffliposomes,erent applications, includingdendrimers, diagnosis and and nanosized therapy inorganic and flow materials investigation, [1]. Organic areNPs relatedvary in their to configuration activity in different of the high surface-to-volumebiological systems proportions including of penetration NPs as a depths potential in tissues system and their for thesetoxicity strategies. and targeting Structures efficiency such as core/shell[2]. NPs Inorganic can show NPs improvedregularly display properties novel physical and increased properties usefulnessas their size is due close to to theirnanometer changed scale chemical measurements. For instance, the extraordinary physical and chemical properties of these NPs may distinctionprompt and nanostructuredfuture applications in parts. drug delivery This article and biomedical therefore imaging. features Plenty an of assortment sophisticated ofand structures and propertiesdifferent that applications, can be acknowledged including diagnosis in materials and therapy dependent and flow oninvestigation, inorganic are NPs related and to focuses on discussingconfiguration major inquiries of the broughthigh surfac upe-to-volume in controlling proportions these of properties. NPs as a potential system for these Typicalstrategies. characteristics Structures such of inorganic as core/shell nanomaterials, NPs can show improved such as properties ease of and fabrication, increased usefulness modification and due to their changed chemical distinction and nanostructured parts. This article therefore features an functionalization,assortment simpleof structures preparation and properties methods, that can resistance be acknowledged to microbial in materials attacks, dependent high stability on and suitable sizeinorganic for cells NPs(plasma and focuses membrane on discussing below major100 inquiries nm), brought a low toxicityup in controlling profile, these biocompatibility, properties. and having a hydrophilicTypical characteristics nature, make of inorganic them suitablenanomaterials, as drug such carriersas ease of fabrication, [3]. Moreover, modification these and NPs can be biodegradable,functionalization, non-toxic, simple non-immunogenic preparation methods, responsive, resistance have to microbial a high attacks, loading high capacity, stability andand have the suitable size for cells (plasma membrane below 100 nm), a low toxicity profile, biocompatibility, and capacity for controlled drug release. These characteristics are desired for biomedical applications having a hydrophilic nature, make them suitable as drug carriers [3]. Moreover, these NPs can be in additionbiodegradable, to properties non-to suchxic, non-immunogenic as magnetism. responsive, However, have in practice,a high loading it is capacity, not easy and to have fabricate the ideal NPs whichcapacity have allfor thecontrolled desired drug properties release. These [4, 5characteristics] and some are NPs desired are indeed for biomedical not suitable applications for biomedicalin applications.addition To improveto properties their such biocompatibility, as magnetism. However, protective in practice, coatings
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