nanomaterials Review Biocompatibility of Biomaterials for Nanoencapsulation: Current Approaches Bwalya A. Witika 1 , Pedzisai A. Makoni 1 , Scott K. Matafwali 2 , Billy Chabalenge 3 , Chiluba Mwila 4 , Aubrey C. Kalungia 4 , Christian I. Nkanga 5 , Alain M. Bapolisi 6 and Roderick B. Walker 1, * 1 Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Makhanda 6140, South Africa; bwawitss@gmail.com (B.A.W.); p.makoni@ru.ac.za (P.A.M.) 2 Department of Basic Sciences, School of Medicine, Copperbelt University, Ndola 10101, Zambia; scott.matafwali@cbu.ac.zm 3 Department of Market Authorization, Zambia Medicines Regulatory Authority, Lusaka 10101, Zambia; bchabalenge@zamra.co.zm 4 Department of Pharmacy, School of Health Sciences, University of Zambia, Lusaka 10101, Zambia; chiluba.mwila@unza.zm (C.M.); ckalungia@unza.zm (A.C.K.) 5 Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences, University of Kinshasa, P.O. Box 212, Kinshasa XI, Democratic Republic of the Congo; christian.nkanga@unikin.ac.cd 6 Department of Chemistry, Faculty of Science, Rhodes University, Makhanda 6140, South Africa; g18b2522@campus.ru.ac.za * Correspondence: r.b.walker@ru.ac.za Received: 20 July 2020; Accepted: 9 August 2020; Published: 22 August 2020   Abstract: Nanoencapsulation is an approach to circumvent shortcomings such as reduced bioavailability, undesirable side effects, frequent dosing and unpleasant organoleptic properties of conventional drug delivery systems. The process of nanoencapsulation involves the use of biomaterials such as surfactants and/or polymers, often in combination with charge inducers and/or ligands for targeting. The biomaterials selected for nanoencapsulation processes must be as biocompatible as possible. The type(s) of biomaterials used for different nanoencapsulation approaches are highlighted and their use and applicability with regard to haemo- and, histocompatibility, cytotoxicity, genotoxicity and carcinogenesis are discussed. Keywords: biocompatibility; haemocompatibility; histocompatibility; cytotoxicity; genotoxicity; nanospheres; liposomes; micelles; nanocrystals; nanoencapsulation; polymers; surfactants 1. Introduction The development of smart medicines has arisen for many reasons, including the challenge associated with using compounds that exhibit poor intrinsic solubility, resistance due chronic use and improving the side effect profile(s) through targeted delivery [1]. Many of these shortcomings can be overcome using nanotechnology, which is defined as the engineering and manufacture of materials at an atomic or molecular scale, resulting in the production of nanoparticles [2] that are broadly defined as materials with dimensions <1000 nm [3–5]. Nanocrystals and micelles are examples of smart nano-drug delivery approaches used for the enhancement of solubility of many active pharmaceutical ingredients (APIs) [6–8]. More specifically, nanocrystals of itraconazole [9,10], clarithromycin [11–13], luliconazole [14] and micelles of curcumin [15], gliclazide [16] and glibenclamide [17] have been manufactured to improve the intrinsic solubility of these compounds. Liposomes [18,19], nanocrystals [20–22], micelles [23–25], nanospheres and nanocapsules [26–28], solid lipid nanoparticles (SLNs) and nano-lipid carriers (NLCs) [29–31] Nanomaterials 2020, 10, 1649; doi:10.3390/nano10091649 www.mdpi.com/journal/nanomaterials