Study On Preparation Of Hydrophilic Drug-loaded Nanocapsules By Double-emulsion Method

In order to solve the problems such as short effect time and side effects caused by traditional ways of administration,the sustained-release drug delivery system have caught much attention of researchers,especially biodegradable polymer-based micro/nano carriers,among which PLA/PLGA and their block copolymers stand out because of their good biocompatibility and modifiability.Water-oil-water(W/O/W)double emulsion-solvent evaporation method is commonly used to prepare microspheres or nanocapsules loading hydrophilic drugs.However,there are still few researches on the preparation of nanocapsules loading small hydrophilic molecule drug lidocaine hydrochloride by double emulsion method,not to mention the study of the comparasion of the double emulsion method in loading hydrophilic drugs with different molecule weight.In this research,PLA/PLGA-b-MPEG polymers were choosen as carriers to load drugs by double emulsion method.We first used a kind of local anesthetic——lidocaine hydrochloride(LDH)as model drug to prepare the LDH-Nanocapsules.Morphology and mean particle size were characterized.In addition,the influences of different parameters on properties of the nanocapsules were investigated.We also designed orthogonal experiment to optimize the parameters of preparation.Furthermore,we also prepared doxorubicin hydrochloride(DOX)-Nanacapsules and bovine serum albumin(BSA)-Nanacapsules.The encapsulation efficiency of BSA-Nanocapsules is more than 90.0 wt%,which was much higher than that of LDH-Nanocapsules(26.4 wt%)and DOX-Nanacapsules(38.9wt%),further confirming that using this double emulsion method to prepare small hydrophilic molecules is still facing challenges.Release behavior is one of the most important performance index of sustained-release drug delivery system.In this research,we used dialysis method to explore the in vitro release behavior of the aforementioned prepared LDH-Nanocapsules.A release curve can be represented by accumulated release amount at each point,and fitted by kinds of release kinetics models.The influences of different parameters on the release behavior were also investigated.To conclude,LDH-Nanocapsules with encapsulation efficiency of 26.4 wt% and drug loading of 6.5wt% were prepared,of which the particle size was within the range of 100.0-400.0nm.They could release slowly during 20 days,showing a good application prospect in the field of anesthesia and analgesic.