A comparative study on solubility improvement of tetracycline and dexamethasone by poly(propylene imine) and polyamidoamine dendrimers: An insight into cytotoxicity and cell proliferation

Abstract

Many of new chemical discovered in pharmaceutical industry are hydrophobic compounds. Various techniques have been used to overcome solubility problems of hydrophobic drugs in aqueous media. In the meantime, dendrimers have been considered for sustainability, nanoscale size, high carry capacity, tunable terminal functional groups in terms of drug delivery and solubility. In this work, we have synthesized poly(propylene imine) (PPI) dendrimer up to fifth generation using reduction of nitrile groups after Michael addition and also, polyamidoamine (PAMAM) dendrimer up to fourth generation using Michael addition and amidation reactions. fourth and fifth generations of PPI dendrimer and fourth and third generations of PAMAM dendrimer in different concentrations were used to evaluate the solubility of two hydrophobic drugs (tetracycline and dexamethasone). Furthermore, cytotoxicity of dendrimers and dendrimers/drugs hybrids was studied. The results showed that with increasing concentrations and also the generation of dendrimers, the solubility of these two hydrophobic drugs was increased. Cytotoxicity study through MTT assay against Osteoblast-like cell line showed that dendrimers were relatively cytotoxic where adding dexamethasone caused higher cytotoxicity. However, tetracycline showed no significant effect on cytotoxicity whereas prevented cell proliferation. K E Y W O R D Scell proliferation, cytotoxicity, dendrimer, hydrophobic drug, solubility

Polyvinylpyrrolidone K-30-Based Crosslinked Fast Swelling Nanogels: An Impeccable Approach for Drug’s Solubility Improvement

“…self-emulsifying drug delivery system (SEDDS), inclusion complexation with cyclodextrins, dendrimers, and nanocapsule [18][19][20].…”

Synthesis and characterization of poly(propylene imine) dendrimers, as nanocarriers of Benznidazole: an in vitro controlled release assay

“…The dendrimer cores are formed of tertiary amines; therefore, they tend to retain the BZN particles, through hydrogen bridge type interactions. In addition, the cavities of the PPI dendrimer are highly hydrophobic, which increases the possibility of interaction with hydrophobic drugs such as BZN (33). According to the literature, the amount of host molecules entrapped in the dendrimer is proportional to the shape and size of the molecule to be encapsulated, as well as to the shape and size of the available internal cavities of the dendritic structure (34).…”

Dexamethasone-Loaded Bioactive Coatings on Medical Grade Stainless Steel Promote Osteointegration

“…CMC solution (containing 0.5 wt.% CMC) was prepared using CMC (low viscosity, Sigma Aldrich, St. Louis, MO, USA) and ultrapure water. As the solubility of DEX in water is very low (89 mg/L at 25 • C) [33,37], increased solubility can be achieved with the addition of β-CD [38,39]. β-CD with a purity ≥97% was used for this purpose (Sigma Aldrich).…”

“…Among these, its low solubility in water renders its inclusion in formulations harder than expected [33]. Due to the latter, solutions for its functionalisation were developed, including combinations of different polymers [33], the use of solubilizing agents [34,35], and the preparation of formulations based on "bimodal" materials with hydrophilic and lipophilic parts (e.g., cyclodextrins (CDs)) [36]. Although the literature reports some examples of DEX combinations, to the best of our knowledge, our study is the first to combine β-cyclodextrin (β-CD) with DEX to prepare coatings on metal implants for orthopedic applications.…”