Conjugation And Evaluation of Novel Polymeric Naproxen-PEG Esters

07 March 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Nonsteroidal anti-inflammatory drugs (NSAID) are commonly used and prescribed across the globe. A defining characteristic of NSAIDs is their poor water solubility; therefore, in a practical setting this translates directly to poor systemic absorption in the body1. The ability of a drug to effectively enter and carry out microscopic processes within cells depends on its ability to transverse the lipid membrane surrounding cells. The metric used to evaluate this capacity is called the partition coefficient, or the logP. The logP is the logarithm of concentration of a molecule between octanol and water partitions, where membrane permeability can be evaluated from this value as octanol is comparable to the cell membrane2. A logP above >0 indicates a preferential solubility in lipids, a high logP is correlated with poor solubility and absorption3.It is recommended that a drug must be overall lipophilic but still maintain aqueous solubility4. Naproxen is an NSAID that is used to treat inflammation found in many common illnesses. Naproxen has a logP value of 3.3; however a logP value <2.7 is best for traversing barriers in the body such as the blood brain barrier4. By adapting a novel synthesis method to perform the esterification of naproxen to polyethylene glycol, the aqueous solubility can be improved. Thin-layer chromatography studies confirmed an decrease in the logP value. Spectrophotography drug release and solubility tests of the conjugate form reveal a prolonged release time. This indicates the successful development and distribution of the novel molecule. The lower logP value also corresponds to better oral absorption and uptake, therefore, naproxen-PEG ester demonstrates capacity as a drug delivery system with increased therapeutic efficacy.


Drug Solubility
Partition Coefficient
Improved Solubility
Drug Evaluation
Drug Esters
PEG Conjugation


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