ABSTRACT
In conventional message communication systems, the practice of multi-message multi-receiver signcryption communication encounters several challenges, including the vulnerability to Key Generation Center (KGC) attacks, privacy breaches and excessive communication data volume. The KGC necessitates a secure channel to transmit partial private keys, thereby rendering the security of these partial private keys reliant on the integrity of the interaction channel. This dependence introduces concerns regarding the confidentiality of the private keys. Our proposal advocates for the substitution of the KGC in traditional certificateless schemes with blockchain and smart contract technology. Parameters are publicly disclosed on the blockchain, leveraging its tamper-proof property to ensure security. Furthermore, this scheme introduces conventional encryption techniques to achieve user identity privacy in the absence of a secure channel, effectively resolving the issue of user identity disclosure inherent in blockchain-based schemes and enhancing communication privacy. Moreover, users utilize smart contract algorithms to generate a portion of the encrypted private key, thereby minimizing the possibility of third-party attacks. In this paper, the scheme exhibits resilience against various attacks, including KGC leakage attacks, internal privilege attacks, replay attacks, distributed denial of service attacks and Man-in-the-Middle (MITM) attacks. Additionally, it possesses desirable security attributes such as key escrow security and non-repudiation. The proposed scheme has been theoretically and experimentally analyzed under the random oracle model, based on the computational Diffie-Hellman problem and the discrete logarithm problem. It has been proven to possess confidentiality and unforgeability. Compared with similar schemes, our scheme has lower computational cost and shorter ciphertext length. It has obvious advantages in communication and time overhead.
ABSTRACT
The association rate constant and dissociation rate constant are important parameters of the drug-cyclodextrin supermolecule systems, which determine the dissociation of drugs from the complex and the further in vivo absorption of drugs. However, the current studies of drug-cyclodextrin interactions mostly focus on the thermodynamic parameter of equilibrium constants (K). In this paper, a method based on quantitative high performance affinity chromatography coupled with mass spectrometry was developed to determine the apparent dissociation rate constant (k(off,app)) of drug-cyclodextrin supermolecule systems. This method was employed to measure the k(off,app) of meloxicam and acetaminophen. Firstly, chromatographic peaks of drugs and non-retained solute (uracil) on ß-cyclodextrin column at different flow rates were acquired, and the retention time and variance values were obtained via the fitting the peaks. Then, the plate heights of drugs (H(R)) and uracil (H(M,C)) were calculated. The plate height of theoretical non-retained solute (H(M,T)) was calculated based on the differences of diffusion coefficient and the stagnant mobile phase mass transfer between drugs and uracil. Finally, the k(off,app) was calculated from the slope of the regression equation between (H(R)-H(M,T)) and uk/(1+k)2, (0.13 ± 0.00) s(-1) and (4.83 ± 0.10) s(-1) for meloxicam and acetaminophen (control drug), respectively. In addition, the apparent association rate constant (k(on,app)) was also calculated through the product of K (12.53 L x mol(-1)) and k(off,app). In summary, it has been proved that the method established in our study was simple, efficiently fast and reproducible for investigation on the kinetics of drug-cyclodextrin interactions.
Subject(s)
Thiazines/chemistry , Thiazoles/chemistry , beta-Cyclodextrins/chemistry , Acetaminophen/chemistry , Chromatography, Affinity , Drug Interactions , Kinetics , Mass Spectrometry , Meloxicam , ThermodynamicsABSTRACT
The release behavior of single pellet was investigated by LC/MS/MS method with tamsulosin hydrochloride (TSH) as the model drug of the research and then the pellets were divided into four groups according to the drug loading. Comparison of dissolution profiles of each group and capsule were performed using f1 and f2 factor methods to study the difference and similarity. The release profiles of single pellet, each group and capsule were analyzed using principle component analysis (PCA). The particle system was built through Matlab to get the target release profile. The result of this research demonstrated the release behavior of single pellet correlated well with the drug loading. While the dissolution profile of capsule as a reference, the similarity factor of dissolution profiles of the lower drug loading groups were 62.2, 67.1, 53.9, respectively and, 43.3 for highest drug loading group. The particle systems with different pellet distribution and same release profiles were built through release behavior of single pellet. It is of significance to investigate the release behavior of single pellets for studying the release regularity of multiple-unit drug delivery system.