Pharmaceutical NanotechnologyThe evaluation of the biomedical effectiveness of poly(amido)amine dendrimers generation 4.0 as a drug and as drug carriers: A systematic review and meta-analysis
Graphical abstract
Introduction
Dendrimers are hyperbranched, monodisperse, three-dimensional macromolecules with defined molecular weight and host–guest entrapment properties. They allow the precise control of size, shape and placement of functional groups and combine typical characteristics of small organic molecules and polymers that result in special physical and chemical properties. Poly(amido)amine (PAMAM) dendrimers represent a new class of polymers (Tomalia et al., 1985, Tomalia et al., 1986, Tomalia et al., 1990). They are also known as starburst dendrimers. The term ‘starburst’ is a trademark of the Dow Chemicals Company. As the chains growing from the core molecule become longer and more branched, generation 4.0 and higher dendrimers adopt a globular structure (Fig. 1).
The manufacturing process is a series of repetitive steps starting with a central initiator core. Classically, dendrimers are synthesized by sequential steps, by divergent (Tomalia et al., 1985) or convergent (Hawker et al., 1990) methods. In the divergent techniques, dendrimer grows outwards from a multifunctional core molecule. The core molecule reacts with monomer molecules containing one reactive and two dormant groups giving the first generation dendrimer. The divergent approach is successful for the production of large quantities of dendrimers. The convergent methods were developed as a response to the weaknesses of the divergent synthesis. In the convergent approach, the dendrimer is constructed stepwise, starting from the end groups and progressing inwards.
Section snippets
PAMAM G4 as a drug
We performed a literature search in PubMed and Embase from April 2008 to April 2013. PubMed was the main search engine for primary research, supplemented by Embase and by direct consultation of specialty journals such as International Journal of Pharmaceutics, International Journal of Nanomedicine and Cell Biology International.
The dendrimer PAMAM G4 might be a useful as drug, for example, in diabetic rats. PAMAM dendrimers generation G 4.0 dendrimers reduce blood hyperglycaemia and restore
PAMAM G4 as a drug carriers
An ideal drug carrier vehicle must be biochemically inert and non-toxic, while protecting the payload (drug) from dissociation until it reaches the target site. PAMAM G4 dendrimers as drug carriers were assessed for targeting nonsmall cell lung cancer (Liu et al., 2011a). A novel nonsmall cell lung cancer-targeting peptide (LCTP) and a fluorescence-labeled molecule (FITC) were conjugated to an acetylated polyamidoamine (PAMAM) G4 dendrimer to form a PAMAM–Ac–FITC–LCTP conjugate. The results
Results
The analysis of the data obtained from the few works reports concerning the treatment with medical drugs is possible through the introduction of standardized data, the calculation of indicators and combining the results of several tests and test parameters in order to create a comprehensive test by applying the drug effect estimator (carrying out) by conducting a meta-analysis. Data standardization is necessary due to the results presented in different units, and also the presence of the
Discussion
Nanotechnology plays a unique instrumental role in the revolutionary development of drugs, drug delivery and diagnosis. Over the past years, we have made great progress in developing nanomolecular devices. A rapid increase of interest in the nanomedicine of dendrimers has been observed since the first dendrimers were synthesized. The polyamidoamine dendrimers (PAMAM) were synthesized at the end of the last century (Tomalia et al., 1985, Tomalia et al., 1986, Tomalia et al., 1990). The
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