Abstract
Clinical applications of many small molecules are limited due to poor solubility and lack of controlled release besides lack of other desirable properties. Experimental and computational studies have reported on the therapeutic potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers in pre-clinical and clinical settings. Besides formulation strategies, factors such as pH, PAMAM dendrimer generation, PAMAM dendrimer concentration, nature of the PAMAM core, special ligand and surface modifications of PAMAM dendrimer have an influence on drug solubility and other recommendable pharmacological properties. This review, therefore, compiles the recently reported applications of PAMAM dendrimers in pre-clinical and clinical uses as enhancers of solubility and other desirable properties such as sustained and controlled release, bioavailability, bio-distribution, toxicity reduction or enhancement, and targeted delivery of small molecules with emphasis on cancer treatment.
Highlights
In order for a drug to produce a desired therapeutic effect, it is required to reach the targeted site in the right amount and dosage
The present review covers the recent applications of PAMAM dendrimers as drug solubilization agents for poorly soluble small molecules and enhancement of other desirable pharmacological properties with emphasis on applications giving emphasis on cancer treatment, with some highlights on anti-inflammatory, antihypertensive, retinal, antifungal, antioxidant, and antiarthritis drugs
asymmetric bow-tie PAMAM dendrimer (ABTD)-TTC-1 further exhibited a remarkable selectivity to cancer cells being >1000 times higher compared to human normal cells, thereby presenting the potential of ABTD-based tumor-targeted drug-delivery systems [31]
Summary
In order for a drug to produce a desired therapeutic effect, it is required to reach the targeted site in the right amount and dosage. Solubility is an important parameter required to achieve the concentration of drugs needed for systemic circulation to produce the desired therapeutic effects. Dendrimers have gained significant attention in biomedical applications as solubility enhancers of poorly soluble molecules [2,3]. Previous reviews focused mainly on synthesis, general properties, and applications of dendrimers as drug delivery systems [13,15,16,17,18,19,20,21,22,23]. The present review covers the recent applications of PAMAM dendrimers as drug solubilization agents for poorly soluble small molecules and enhancement of other desirable pharmacological properties with emphasis on applications giving emphasis on cancer treatment, with some highlights on anti-inflammatory, antihypertensive, retinal, antifungal, antioxidant, and antiarthritis drugs. Experimental Insights on PAMAM-Drug Interactions for Enhanced Solubility and Other
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