Hard, Soft, and Hard-and-Soft Drug Delivery Carriers Based on CaCO3 and Alginate Biomaterials: Synthesis, Properties, Pharmaceutical Applications

Because free therapeutic drug molecules often have adverse effects on normal tissues, deliver scanty drug concentrations and exhibit a potentially low efficacy at pathological sites, various drug carriers have been developed for preclinical and clinical trials. Their physicochemical and toxicological properties are the subject of extensive research. Inorganic calcium carbonate particles are promising candidates as drug delivery carriers owning to their hardness, porous internal structure, high surface area, distinctive pH-sensitivity, low degradability, etc, while soft organic alginate hydrogels are also widely used because of their special advantages such as a high hydration, bio-adhesiveness, and non-antigenicity.

Here, we review these two distinct substances as well as hybrid structures encompassing both types of carriers. Methods of their synthesis, fundamental properties and mechanisms of formation, and their respective applications are described. Furthermore, we summarize and compare similarities versus differences taking into account unique advantages and disadvantages of these drug delivery carriers. Moreover, rational combination of both carrier types due to their performance complementarity (yin-&yang properties: in general, yin is referred to for definiteness as hard, and yang is broadly taken as soft) is proposed to be used in the so-called hybrid carriers endowing them with even more advanced properties envisioned to be attractive for designing new drug delivery systems.

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The internal microenvironment of the human body is a complex circulatory system with some exclusivity to foreign objects. This function protects the human body from viruses, while having the opposite effect on the treatment of diseases to some extent. One of the issues is the decomposition capability of enzymes in body fluids which would consume drugs before reaching the pathological site, thereby reducing the effective drug concentration and therapeutic effect. Simultaneously, the absorption of free drugs by normal cells or tissues during delivery will impose serious adverse effects to human body, which is a widespread problem with current chemotherapeutic drugs and in the area of nanomedicine in general.
In view of this, various multifunctional drug delivery carriers capable of encapsulating therapeutic drugs molecules have emerged or have been developed. These carriers allow the drug to selectively kill abnormal cells without adverse effects on normal cells, thus minimizing side effects on the human body. Numerous drug delivery carriers with favorable biological properties have been developed, including carriers belonging to two main classes: inorganic and organic. The former one, inorganic particles, includes carriers such as quantum dots (QD), gold (Au) and silver (Ag) metal nanoparticles, clays, carbon, porous silica (SiO2), hydroxyapatite (HA), and calcium carbonate (CaCO3), etc. The latter one, organic particles, comprises of an equally impressive range of carriers, such as liposomes, polymer micelles, dendrimers, protein conjugates, red blood cells (RBCs), cell penetrating peptides, layer-by-layer (LbL) capsules and alginate (Alg) or alginate hydrogel (Alg-Hs) particles, etc.
In this review, we describe one candidate from each category: CaCO3, an inorganic carrier, generally referred to as hard, and Alg, an organic carrier, generally referred to as soft; a combination of CaCO3 on Alg and Alg in CaCO3, generally referred to as hard-and-soft or hybrid , is also discussed. Peculiarly, although they are quite different, there are similarities and, naturally, dissimilarities between these types of carriers. However, first we give a short overview of major types of both inorganic and organic drug delivery carriers.


Huang, Y.; Cao, L.; Parakhonskiy, B.V.; Skirtach, A.G. Hard, Soft, and Hard-and-Soft Drug Delivery Carriers Based on CaCO3 and Alginate Biomaterials: Synthesis, Properties, Pharmaceutical Applications. Pharmaceutics 202214, 909. https://doi.org/10.3390/pharmaceutics14050909

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