Abstract
Polyamidoamine (PAMAM) dendrimers are extensively researched as potential drug delivery system thanks to their desirable features such as controlled and stable structures, and ease of functionalization onto their surface active groups. However, there have been concerns about the toxicity of full generation dendrimers and risks of premature clearance from circulation, along with other physical drawbacks presented in previous formulations, including large particle sizes and low drug loading efficiency. In our study, carboxyl-terminated PAMAM dendrimer G3.5 was grafted with poly (ethylene glycol) methyl ether (mPEG) to be employed as a nano-based drug delivery system with great cytocompatibility for the delivery of carboplatin (CPT), a widely prescribed anticancer drug with strong side effects so that the drug will be effectively entrapped and not exhibit uncontrolled outflow from the open structure of unmodified PAMAM G3.5. The particles formed were spherical in shape and had the optimal size range (around 36 nm) that accommodates high drug entrapment efficiency. Surface charge was also determined to be almost neutral and the system was cytocompatible. In vitro release patterns over 24 h showed a prolonged CPT release compared to free drug, which correlated to the cytotoxicity assay on malignant cell lines showing the lack of anticancer effect of CPT/mPEG-G3.5 compared with CPT.
Highlights
Among the second generation of platinum-containing drugs, carboplatin (CPT) is known as the most important one that is widely used in clinics for the treatment of cancer [1]
In spite of having a similar molecular mechanism of action in cancer cells, CPT exhibits lower reactivity and toxicity compared to the first generation platinum-containing cisplatin, with no nephrotoxicity, ototoxicity, and neurotoxicity [5]
Synthesis of Carboxyl-Terminated PAMAM G3.5 Dendrimer Half-generation carboxyl-terminated PAMAM G3.5 was synthesized from the EDA core by a divHearglfe-gnetnaepraptrioanchcarthboatxyelm-teprlmoyinsatwedo PcAonMseAcMutiGve3.c5hwaians-fsoyrnmthinegsizredacftrionms,thineclEuDdAingcoMreicbhyaeal divergent approach that employs two consecutive chain-forming reactions, including Michael addition reaction and amidation reaction, as reported previously by Donald Tomalia with minor modification
Summary
Among the second generation of platinum-containing drugs, carboplatin (CPT) is known as the most important one that is widely used in clinics for the treatment of cancer [1]. Half generation PAMAM dendrimer with carboxylate groups on the surface does not interfere with cell membranes and is preferable for drug delivery. Non-specific interaction between serum proteins and PAMAM was prevented by PEG, averting the uptake of PAMAM dendrimer by the reticuloendothelial system [35], reducing renal clearance, and improving the circulating half-life [36,37]. After loading of CPT, the particle size saw another increase to 36.0 ± 0.2 nm, which falls into the optimal size range for nanocarriers This indicates an improvement in controlling the size of dendrimer particles, as previous study on PEG-modified G3.5 resulted in size that was bigger than desired [26], while aInnto. CCeellllvviiaabbiilliittyyaafftteerr2244hh iinn ppeerrcceennttaaggee aanndd fflluuoorreesscceenntt ssiiggnnaallss ooff HHeeLLaa ((AA,,CC--bb)) aanndd AA554499 ((BB,,CC--cc)) wwiitthh CCPPTT ((ssqquuaarree)) aannddCCPPTT//mmPPEEGG-G-G33.5.5-C-CPPTT(r(orouunndd););CCelellvl ivaibaibliitliytyininpeprecrecnetnatgaegaeftaefrte2r42h4 ohf oLf9L2992(9C(-Ca)-aw)iwthitmh PmEPGE-GG-3G.53(.5w(hwitheitdeodt)oat)nadnCdPCTP/mT/PmEPGE-GG3-G.53(.b5l(abclkacdkodt)ot)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
