**Magdalena Martinka Maksymiak 1,\*, Magdalena Zi ˛eba 1, Arkadiusz Orchel 2, Monika Musiał-Kulik 1, Marek Kowalczuk <sup>1</sup> and Grazyna Adamus 1,\***


Received: 3 July 2020; Accepted: 11 September 2020; Published: 18 September 2020

**Abstract:** This article reports the studies on bioactive (co)oligoesters towards their use as controlled delivery systems of p-anisic acid. The objects of the study were oligo[3-hydroxy-3-(4-methoxybenzoyloxymethyl)propionate], (p-AA-CH2-HP)n oligoester, and oligo[(3-hydroxy-3-(4-methoxybenzoyloxymethyl)propionate)-co-(3-hydroxybutyrate)] [(p-AA-CH2-HP)x-co-(HB)y (co)oligoesters containing p-anisic acid moiety (p-AA, as the bioactive end and side groups) connected to the polymer backbone through the susceptible to hydrolysis ester bonds. A thorough insight into the hydrolysis process of the bioactive (co)oligoesters studied has allowed us to determine the release profile of p-AA as well as to identify polymer carrier degradation products. The p-AA release profiles determined on the basis of high-performance liquid chromatography (HPLC) measurements showed that the release of the bioactive compound from the developed (co)oligoester systems was regular and no burst effect occurred. Biological studies demonstrated that studied (homo)- and (co)oligoesters were well tolerated by HaCaT cells because none of them showed notable cytotoxicity. They promoted keratinocyte growth at moderate concentrations. Bioactive (co)oligoesters containing p-anisic acid moiety had somewhat decreased cell proliferation at the highest concentration (100 μg/mL). The important practical inference of the current study is that the (co)oligoesters developed have a relatively large load of the biologically active substance (p-AA) per polymer macromolecule, which unlocks their potential application in the cosmetic industry.

**Keywords:** polyhydroxyalkanoates; oligo(3-hydroxy-3-(4-methoxybenzoyloxymethyl)propionate); bioactive (co)oligoesters; p-anisic acid derivatives; hydrolytic degradation; cosmetic delivery system; ESI-MS; multistage mass spectrometry
