Self-assembly of drug-polymer complexes: a spontaneous nanoencapsulation process monitored by atomic force microscopy

Since hydrophilic matrices were proposed for controlled drug delivery, many polymeric excipients have been studied to make drug release fit the desired profiles. It has been pointed out that lambda-carrageenan, a sulfated polymer from algae, can suitably control the release rate of basic drugs from hydrophilic matrices. Furthermore, the relevance of hydrophobic interactions in drug-polymer aqueous systems has already been demonstrated, although no references to morphological features as well as to the kinetics of the interaction complexes formation have been published to date. In this work, we propose a method to monitor the topographical evolution of the interaction between lambda-carrageenan and dexchlorpheniramine maleate, in order to determine how the release profiles can be so easily controlled. For this purpose, solutions of both polymer and drug were prepared at very low concentration. Solutions were mixed and small volumes were taken every hour for over a period of 24 h and subsequently analyzed. The characterization technique used, atomic force microscopy, provides a high resolution, allowing plotting of three-dimensional images of the sample morphology within the nanometric scale. The results demonstrate that lambda-carrageenan is able to nanoencapsulate spontaneously dexchlorpheniramine maleate molecules, which offers the possibility of controlling the release rate of the drug with no need of complex technological processes. Moreover, this work demonstrates the suitability of atomic force microscopy for the specific case of the on-time monitoring of interaction processes that occur in pharmaceutical systems.