Cyclodextrin⁻Drug Inclusion Complexes: In Vivo and In Vitro Approaches

Abstract

This review aims to provide a critical review of the biological performance of natural and synthetic substances complexed with cyclodextrins, highlighting: (i) inclusion complexes with cyclodextrins and their biological studies in vitro and in vivo; (ii) Evaluation and comparison of the bioactive efficacy of complexed and non-complexed substances; (iii) Chemical and biological performance tests of inclusion complexes, aimed at the development of new pharmaceutical products. Based on the evidence presented in the review, it is clear that cyclodextrins play a vital role in the development of inclusion complexes which promote improvements in the chemical and biological properties of the complexed active principles, as well as providing improved solubility and aqueous stability. Although the literature shows the importance of their ability to help produce innovative biotechnological substances, we still need more studies to develop and expand their therapeutic properties. It is, therefore, very important to gather together evidence of the effectiveness of inclusion complexes with cyclodextrins in order to facilitate a better understanding of research on this topic and encourage further studies.

Keywords: biological assays; cyclodextrins; drug delivery; inclusion complexes; pharmaceutical technology; substances.

Figure 1

(A) α-, β-, and γ-CD (cyclodextrin) molecules; (B) Representation of compound inclusion complex in cyclodextrin [5,14].

Figure 2

Quantities of in vivo studies performed with substances in an inclusion complex with cyclodextrins, according to works published in the literature in the years 2001 to 2019.

Figure 3

Copaifera multijuga oleoresin, inclusion complex and its main major compound β-caryophyllene and anti-inflammatory activity in vivo [32].

Figure 4

(A) Ten possible interactions of limonene (LIM) and CDs obtained through molecular modeling. The green space represents the CD cavity; (B) Response time evaluation after administration of vehicle, LIM (50 mg/kg), LIM-βCD (50 mg/kg) or TMR (4 mg/kg) on mechanical hyperalgesia induced by acidic saline in mice. The values are expressed as mean ± SEM. * p < 0.05, ** p < 0.01 or *** p < 0.001 vs. Control group. # p < 0.05, ## p < 0.01 or ### p < 0.001 vs. LIM group (two-way analysis of variance ANOVA followed by Bonferroni test); (C) Fos-positive cells in the lumbar spinal cord. Vehicle (D), LIM (50 mg/kg) (E), LIM-βCD (50 mg/kg) (F) were administered 60 min before perfusion. The values are expressed as mean ± SEM (n = 6, per group). *** p < 0.001 vs. control group (one-way ANOVA followed by Bonferroni test) [42]. Scale bar: 20 μm.

Figure 5

Quantities of in vitro studies performed with substances in inclusion complexes with cyclodextrins, according to works published in the literature from 2001 to 2019.