Application of the central composite design to optimize the preparation of novel micelles of harmine

Abstract

Lactose-palmitoyl-trimethyl-chitosan (Lac-TPCS), a novel amphipathic self-assembled polymer, was synthesized for administration of insoluble drugs to reduce their adverse effects. The central composite design was used to study the preparation technique of harmine (HM)-loaded self-assembled micelles based on Lac-TPCS (Lac-TPCS/HM). Three preparation methods and single factors were screened, including solvent type, HM amount, hydration volume, and temperature. The optimal preparation technique was identified after investigating the influence of two independent factors, namely, HM amount and hydration volume, on four indexes, ie, encapsulation efficiency (EE), drug-loading amount (LD), particle size, and polydispersity index (PDI). Analysis of variance showed a high coefficient of determination of 0.916 to 0.994, thus ensuring a satisfactory adjustment of the predicted prescription. The maximum predicted values of the optimal prescription were 91.62%, 14.20%, 183.3 nm, and 0.214 for EE, LD, size, and PDI, respectively, when HM amount was 1.8 mg and hydration volume was 9.6 mL. HM-loaded micelles were successfully characterized by Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and a fluorescencequenching experiment. Sustained release of Lac-TPCS/HM reached 65.3% in 72 hours at pH 7.4, while free HM released about 99.7% under the same conditions.

Modification of Chitosan for the Generation of Functional Derivatives

“…As another example, TMC micelles can be prepared to overcome subasorption and solulibitly problems of specific active molecules, such as insoluble alkaloid, osthole, etc. [185,186]. The use of nanoparticles is not new and current papers deal with specific derivatives such as carboxymethyl CS (CMCS), which are soluble Very recently, Mittal et al [174] published a deep and comprehensive review that scientist readers should adress to fully understand the progress of CS chemistry for use in biomedical fields, as well as the paper of Laroche et al [4], which highlighted the need for an integral approach to comprehend all the potential of CS and its derivatives.…”

“…As another example, TMC micelles can be prepared to overcome subasorption and solulibitly problems of specific active molecules, such as insoluble alkaloid, osthole, etc. [185,186]. The use of nanoparticles is not new and current papers deal with specific derivatives such as carboxymethyl CS (CMCS), which are soluble in both acidic and alkaline solutions, for designing nanotechnology-bases systems based on stimulus-based, diffusion, swelling, or erosion-controlled release [187].…”

Chitosan Based Self-Assembled Nanoparticles in Drug Delivery

“…TMC has been hydrophobically modified with octyl, decanoyl, lauryl, lactose, and palmitoyl substituents for hydroxycamptothecin and harmine encapsulation in the hydrophobic core [182,183,184,185]. N -octyl- N -trimethyl chitosan and N -lauryl- N -trimethyl chitosan were self-assembled in an aqueous medium as micelles of 23.5 and 20.8 nm, while N -decanyl- N -trimethyl chitosan formed micelles with a hydrodynamic diameter of 277.2 nm.…”

“…Hydroxycamptothecin loaded N -alkyl- N -trimethyl chitosan micelles showed a sustained release of the anticancer drug, with improved pharmacokinetic properties and the stability of the camptothecin lactone ring in vivo [182]. On the other hand, the harmine loaded hydrophobically modified TMC released 65.3% of the encapsulated drug in three days at pH 7.4 [183,184].…”

Chitosan Based Self-assembled Nanoparticles in Drug Delivery

“…Hydroxycamptothecin loaded N-alkyl-N-trimethyl chitosan micelles showed sustained release of the anticancer drug with improved pharmacokinetic properties and stability of the camptothecin lactone ring in vivo [183]. On the other hand, harmine loaded hydrophobically modified TMC released a 65.3% of encapsulated drug in 3 days at pH 7.4 [184].…”