N AN O E X P R E S S Open Access
Effects of Micro-environmental pH of
Liposome on Chemical Stability of Loaded
, Xue-Qin Wei
, Shu Zhang, Na Fu, Yun-Feng Lin, Xiao-Xiao Cai
and Qiang Peng
Liposome is a promising carrier system for delivering bioactive molecules. However, the successful delivery of
pH-sensitive molecules is still limited by the intrinsic instability of payloads in physiological environment. Herein,
we developed a special liposome system that possesses an acidic micro-environment in the internal aqueous
chamber to improve the chemical stability of pH-sensitive payloads. Curcumin-loaded liposomes (Cur-LPs) with
varied internal pH values (pH 2.5, 5.0, or 7.4) were prepared. These Cur-LPs have similar particle size of 300 nm,
comparable physical stabilities and analogous in vitro release profiles. Interestingly, the chemical stability of
liposomal curcumin in 50% fetal bovine serum and its anticancer efficacy in vitro are both micro-environmental
pH-dependent (Cur-LP-2.5 > Cur-LP-5.0 > Cur-LP-7.4). This serum stability still has space to be further enhanced to
improve the applicability of Cur-LP. In conclusion, creating an acidic micro-environment in the internal chamber of
liposome is feasible and efficient to improve the chemical stability of pH-sensitive payloads.
Keywords: Liposomes, Nanoparticles, Drug delivery, Controlled release, Curcumin
Liposome, an artificial membrane vehicle, has shown
great potentials in drug delivery due to its drug loading
capacity, biodegradability, and biocompatibility [1–4].
The classic liposome is similar with living cells in struc-
ture, typically consisting of a phospholipid bilayer and
an aqueous inner chamber [5–7]. Due to this structure,
liposome is able to solubilize the insoluble drug molecules
and prevent the loaded drug from the harsh physiological
environment [8–10]. In addition, the surface of liposome
can be modified to prolong the blood circulation time
and/or target specific tissues [11–15]. With these above-
mentioned advantages, various liposome systems have
been clinically approved [8, 9, 16].
Although the delivery of many drugs has been improved
by incorporation into liposome, the delivery of some
pH-sensitive drugs is still limited by the instability of drug
molecule itself in physiological environment (neutral pH
values). Generally, liposome is prepared in a neutral buffer
solution and thus the loaded drug molecules are also in a
neutral environment after incorporation into liposome.
Accordingly, those molecules which are only stable in
acidic environment would be still instable even in the
form of liposome. Therefore, development of a novel
approach for enhancing the stability of pH-sensitive drugs
is of great importance for successful delivery of these
payloads by liposome.
As mentioned above, liposome has an aqueous space
in its inner chamber, which can be used to provide drug
payloads with an acidic micro-environment (Fig. 1). In
this present work, we use curcumin as a model drug and
aim to provide a novel approach for enhancing the
chemical stability of drug molecules loaded in liposome.
It is well known that curcumin is a lipophilic molecule
and has been extensively used in food, medicines, and
cosmetics due to its various bioactivities [17–21]. How-
ever, its delivery is highly limited by its insolubility and
instability in biological fluids [22–25]. So far, it is yet to
fulfill its clinical promise in part due to pH-mediated
instability . Therefore, curcumin is a suitable model
drug for this work.
* Correspondence: email@example.com; firstname.lastname@example.org;
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology,
Sichuan University, No. 14, Block 3, Renmin Road South, Chengdu 610041,
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made.
Shao et al. Nanoscale Research Letters (2017) 12:504