Don't know if the rate of cell uptake of the cisplatin-loaded chitosan nanoparticles can further be optimized or not since chitosan has poor solubility and unmodified chitosan nanoparticles can encapsulate only certain hydrophilic drugs. Very interesting issue.

Better u perform cellular uptake studies with chitosan nanoparticles first, You can use FACS for this. Based on the results u can come to conclusion. Based on your results either chitosan nanoparticles were unable to enter the cells or they have not been fully modified. Similar concentarions in what sense, if 1ug of cisplatin is showing effect on cells than your modified chitosan should have five times less conc in comparison to  free cisplatin, if you are taking 1ug for chitosan thn it is of no use. Hope celluar uptake results will help you out. good luck

What evidence do you have to support:

1. You indeed encapsulated cis-plat?

2. During the prep/purification you retained the amount you think

3. Is you assay for encapsulated cis-plat (vs. free) interference free for chitosan?

4. As mentioned above, the loaded cis0plat indeed gets into cells?

"Taking into consideration that similar concentrations of both free cisplatin and cisplatin-loaded nanoparticles were added." --> I'll assume that the cisplatin already entrapped and drug loading capacity of nanoparticle has been calculated.

As I recall chitosan is having amine group, and since Pt still has vacant orbital I think it is very possible for cisplatin to bind the amine group of chitosan through coordinate covalent bond. That way the cisplatin is strongly bound to chitosan and can not be released to the environment. Moreover, having more crosslinker (especially through covalent bond) will make chitosan nanoparticle to degrade slower.

Update:

It is stated in here that the use of N-trimethyl chitosan is to reduce the risk of the covalent coordinate bonding between chitosan and cisplatin:

https://www.researchgate.net/profile/Riccardo_Leardi/publication/6235217_Preparation_and_evaluation_of_nanoparticles_made_of_chitosan_or_N-trimethyl_chitosan_and_a_cisplatin-alginate_complex/links/09e4150eaffdfbfa05000000.pdf

Another modified chitosan is also used here to reduce the very same risk:

http://www.sciencedirect.com/science/article/pii/S0168365907006785

Article Preparation and evaluation of nanoparticles made of chitosan...

have you try to in vivo experiment? what is your purpose of your research? because using the cell line, treat directly to the cell line due the encapsulate influence the analysis. 

here i attach the paper that assay chitosan-pluronic nanoparticel in preparation in vitro study.

http://www.ncbi.nlm.nih.gov/pubmed/22605934

Yasmine, My sugeestion is, "you have to leave time for encapsulation".

Take finite concentration of nanoparticles and cisplatin (same concentrations of the complex in few number of test tubes) , then observe the changes in encapsulation by varying time.  it can also be analyse using UV-Visible spectrometer after centrifuging the samples at different time interval. Then check for the best encapsulation and also the release ability of chitsan nanoparticles and proceed further with the cell lines.

Usually, it takes time for encapsulating a drug in/onto the nanoparticles. Hope it can give an idea.

As mentioned above, I may be due to non release of cisptn from the nanoparticles. 

Cellular uptake of nanoparticles aslo may play role but if release is there either out of cell or inside of cell then it will give effect. Here we are not observing any effect on cell viability, it means drug release is not taking place. 

The main consideration before doing encapsulation of any drug into a carrier system is to study the physical chemical properties therotically ! Is strong chemical binding will occurs ! Is the drug will be stable in carrier system ? A very short litreture review will help a lot before conducting a research! 

I agree with the above comments.