Presented by: Saduakassova Togzhan Checked: Kondaurov Ruslan

INTRODUCTION The ideal drug delivery system is the one in which the drug delivery profile is able to respond to metabolic states and/or physiological variations. This kind of system relies on two premises: the first is the temporal drug modulation according the physiological needs and the second is the drug distribution on a specific target. Smart polymers, or stimuli-responsive polymers, are in the vanguard of drug administration technology since they have show an active response to small signs and changes in the surrounding environment, which translates into significant changes in their microstructure and in the physiological and chemical proprieties, as desired. In other words, smart polymers are able to respond to a stimulus by showing physical or chemical changes in its behavior as, for example, the delivery of the drug carried by itself.

THERMO-RESPONSIVE POLYMERS These smart polymers are sensitive to the temperature and change their microstructural features in response to change in temperature. These are the most studied, most used and most safe polymers in drug administration systems and biomaterials. Thermo-responsive polymers present in their structure a very sensitive balance between the hydrophobic and the hydrophilic groups and a small change in the temperature can create new adjustments (Bajpai et al., 2008). An important feature of this kind of polymers is the critical solution temperature. If the polymeric solution has a phase

The addition of smart polymers with drug molecules presents as main advantages the ability to administrate an efficient concentration of a certain drug on the right time and spot, reducing the adverse systemic reactions and increasing the patient's adherence to the therapeutic, allowing also the reduction of the drug dose and, consequently, the costs. The signs or stimuli that trigger the structural changes on smart polymers can be classified in three main groups: physical stimuli (temperature, ultrasounds, light, mechanical stress), chemical stimuli These signs or stimuli can be artificially controlled (with a magnetic or electric field, light, ultrasounds, etc.) or naturally promoted by internal physiological environment through a feedback mechanism, leading to changes in the polymer net that allow the drug delivery without any external intervention (for example: pH changes in certain vital organs or related to a disease; temperature change or presence of enzymes or other antigens) or by the physiological condition

Polymers with functional basic groups The polymers named as polybases, or also polycations, such as poly(4-vinylpyridine), poly(2- vinylpyridine) (PVP) and poly(vinylamine) (PVAm), are protonated at high pH values and positively ionized at neutral or low pH values, i.e., they go through a phase transition at pH 5 due to the deprotonation of the pyridine groups (Gil, Hudson, 2004). Other polybases are poly(N,N- dimethylaminoethyl methacrylate) (PDMAEMA) and poly(2- diethylaminoethyl methacrylate) (PDEAEMA), with amino groups in their structure which in acid environments gain protons, and in basic environments release the protons. Examples of polycationic polyelectrolyte polymers are poly(N,N-diakyl aminoethyl methacrylate), poly(lysine) (PL), poly(ethylenimine) (PEI) and chitosan

Polypropylacrylic acid (PPAA) and polyethacrylic acid (PEAA) are examples of pH-responsive polymers that can be used to carry genes. The hemolytic activity of PPAA and PEAA polymers' increases rapidly when the pH decreases to values between 5 and 6 and doesn't present any hemolytic activity at a value of 7.4 (Jeong, Gutowska, 2002). Aguilar et al. (2007) used a biodegradable polycationic polyester polymer named poly(trans-4-hydroxy- L-proline ester) (PHP ester) mixed with hydroxyproline (collagen, gelatin and other peptides). A complex between the soluble polymer, the PHP ester and the DNA was formed and allowed the gene transfection into the mammal's cells (Aguilar et al., 2007). There were also developed polymeric micelles using the copolymer poly(ethylene glycol)-poly(aspartame hydrazine doxorubicin) [(PEG-p(Asp-Hid-dox) mixed with doxorubicin (Aguilar et al., 2007). This copolymer retained the drug and the genes at a physiological pH and released the drug when the pH was below 6.

Fig. 6: Illustrative scheme of the genes' delivery through the pH-responsive polymers, as, for example, the DMAEMA/HEMA nanoparticles