Challenge: To arrive at a more effective drug delivery vehicle, which has lesser adverse effects.
Solution: BIOVIA Discovery Studio
Benefits:
- User friendly workflow to minimize the constructed reverse micelles.
- Simple steps to work with.
- The facility to incorporate the desired molecules as the solvent media.
- Performing energy minimization of the system studied.
- Possibility to calculate the different energies of the system.
CHALLENGE: To construct and analyze the feasibility of a dipeptide micelle as a drug carrier.
This customer utilized the BIOVIA scientific solution–Discovery studio to analyse the possibility of a dipeptide micelle Boc-Ile-Ile-NHMe as a vehicle to carry drug. The dipeptide forming micelle and its aggregational properties were initially analysed experimentally(Table1).
Table 1: Experimentally determined values of the dipeptide
An attempt was made to prove the concept, so the customer has used the BIOVIA scientific solution–Discovery studio to bring in the idea conceived and done the work successfully. In this current study the dipeptide Boc-Ile-IleNHMe(Figure 1) self assembles in chloroform to form stable reverse Micelles at various temperatures ranging from 200 to 350 Kelvin. One of the important applications of reverse micelles is in drug delivery. So, the drugs Ciprofloxacin, Dapsone and Anastrozole(Figure 2) were selected from the Drug bank, based on the inner volume of reverse micelles.
Figure 1: Structure of the dipeptideThe table 1 tabulated with aggregation values are determined experimentally for the given dipeptide. Thus, based on these aggregation values that the dipeptide (drug vehicle) was constructed using Packmol package (Figure 3).
igure 2: Structure of the drugs selected
Figure 3: Structure of the dipeptide micelle with different aggregation numbers.
RESULT: Correlation of free energy value of calculated vs experimental
The drug packed with (Boc-Ile-Ile-NHMe)reverse micelle of different aggregates such as 20 dimer, 43 dimer, 57 dimer, 61dimer, 58dimer, 50 dimer, 40 dimer along with water and chloroform were added in the inner core region and outer surface of reverse micelles.
This complex was minimized and their energy values such as initial energy, potential energy, electrostatic energy, van der waals energy, solvation energy, RMS gradient, nonpolar term, and free energy values were calculated(Table 2). The energy values of the drug vehicle depicted negative energy with stability.
Table 2: The free energy value of reverse micelles comparison
The stable complex of drug vehicle (reverse micelles) is further packed with drugs (Figure 4, 5 and 6) and its stability was studied .
SOLUTION: Therapeutic predictive analysis using Discovery studio simulation tool can be used to predict the reverse micelles as drug carriers.
Drug delivery is daunting task in many diseases through this study. It is depicted that drug vehicle and its stability can be studied, screened, and prioritized. Hence, this customer used the seven different aggregates of the reverse micelle were minimized using the default Steepest Descent first order algorithm. The energy of seven different aggregates, their entropy values, both experimental and theoretical are compared and tabulated in Table 2. The computed value using Discovery studio agrees well with the experimentally determined value. The constructed Reverse Micelles were then constructed with insertion of drugs. Hence, Boc-Ile-Ile-NHMe)reverse micelle can be drug vehicle to deliver the drugs to improve the pharmacological activity with good bioavailability.
Cite: Jaynthy C, Lavnaya G, N. Premjanu, Vignesh Rajamanickam, Dhivya S, “Simulation of a Dipeptide boc-Ile-Ile-NHMe as a drug carrier”, International Journal of Drug Delivery 5 (2013) 81-87.
Acknowledgement: We, team thankful to Dr. Jaytnthy C of Sathyabama University for sharing their one of the research publication a case study
Publication Date : March, 2023
