Search

Jisoo Park,1,* Hai V Ngo,1,* Hyo-Eon Jin,1 Kye Wan Lee,2 Beom-Jin Lee1 1Bioavailability Control Laboratory, College of Pharmacy, Ajou University, Suwon, 16499, Republic of Korea; 2Dongkook Pharmaceutical Co., Ltd, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Beom-Jin Lee, Bioavailability Control Laboratory, College of Pharmacy, Ajou University, Suwon, 16499, Republic of Korea, Tel +82 312193442, Fax +82 312193435, Email bjl@ajou.ac.krPurpose: To conjugate different degree of saturation of C18 fatty acids (stearic acid, oleic acid, and linoleic acid) with the hydroxyl groups of leuprolide acetate (LEU acetate) and to investigate the controlled release and enhanced permeability through self-assembled nanoparticles (L18FNs).Methods: Yamaguchi esterification with benzoyl chloride and DMAP (4-Dimethylaminopyridine) allowed the conjugation of the fatty acid to the hydroxyl group of LEU. The three conjugates were then designated as stearic acid-conjugated LEU, LSC, oleic acid-conjugated LEU, LOC, and linoleic acid-conjugated LEU, LLC, respectively. The conjugates (L18FCs) were purified using preparative HPLC (Prep-HPLC) and identified through various instrumental analyses.Results: The zeta potential, particle size, and morphology of each L18FNs were evaluated. In the case of LSNs, the zeta potential value was relatively low and the particle size was larger than LONs and LLNs owing to the higher hydrophobicity of saturated fatty chain, while the LLNs showed a higher zeta potential and smaller particle size. In human plasma, LLC showed the fastest degradation rate with the highest accumulative drug release. The permeability of L18FNs was analyzed through the Franz diffusion cell experiment, confirming that the degree of saturation of fatty acids affects the permeability of LFNs. While the permeability of LSNs was not significantly enhanced due to higher particle size after nanonization, LONs and LLNs increased

Purpose: To investigate the effects of solvents on the formation of self-assembled nanoni-zation of albumin-oleic acid conjugates (AOCs) using a solvent exchange mechanism for the construction of in situ forming implants (ISFI). Methods: A poorly water-soluble drug, paliperidone palmitate (PPP), was chosen as the model drug. AOC was synthesized with the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) reaction. Dichloromethane, tetrahydrofuran, ethanol, N-methyl-2-pyrrolidone, dimethyl sulfoxide, and deionized water were selected to investigate the formation of self-assembled AOC nanoparticles (AONs). The volume ratios of organic solvents against water could determine the miscibility, injectability, and in situ nanonizing capability without aggregation. Results: As the polarity of the organic solvents increased, the AONs exhibited a spherical shape, and the larger the volume of the solvent, the smaller the size of the AONs. To use AOC in ISFI for controlled release of PPP, poly(d,l-lactide-co-glycolide) (PLGA) was combined with the AOC in 2 mL of N-methyl-2-pyrrolidone and water solution (1.8/0.2 ratio). The release rates of all formulations exhibited similar curve patterns overall but were more controlled in decreasing order as follows: AOC, PLGA, and AOC/PLGA for 14 days. Conclusion: A combined formulation of AOC and PLGA was found to effectively control the initial burst release of the drug.

Yongjun Yu,1 Hai V Ngo,1 Gang Jin,1 Phuong HL Tran,2 Thao TD Tran,3,4 Van Hong Nguyen,5 Chulhun Park,6 Beom-Jin Lee1 1College of Pharmacy, Ajou University, Suwon, 16499, Republic of Korea; 2Deakin University, School of Medicine, Geelong, Australia; 3Institute of Research and Development, Duy Tan University, Danang, 550000, Vietnam; 4The Faculty of Pharmacy, Duy Tan University, Danang, 550000, Vietnam; 5Pharmaceutical Engineering Laboratory, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City, 70000, Vietnam; 6Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, CanadaCorrespondence: Beom-Jin LeeBioavailability Control Laboratory, College of Pharmacy, Ajou University, Suwon, 16499, Republic of KoreaTel +82312193442Fax +82312193435Email bjl@ajou.ac.krPurpose: To investigate the effects of solvents on the formation of self-assembled nanonization of albumin-oleic acid conjugates (AOCs) using a solvent exchange mechanism for the construction of in situ forming implants (ISFI).Methods: A poorly water-soluble drug, paliperidone palmitate (PPP), was chosen as the model drug. AOC was synthesized with the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) reaction. Dichloromethane, tetrahydrofuran, ethanol, N-methyl-2-pyrrolidone, dimethyl sulfoxide, and deionized water were selected to investigate the formation of self-assembled AOC nanoparticles (AONs). The volume ratios of organic solvents against water could determine the miscibility, injectability, and in situ nanonizing capability without aggregation.Results: As the polarity of the organic solvents increased, the AONs exhibited a spherical shape, and the larger the volume of the solvent, the smaller the size of the AONs. To use AOC in ISFI for controlled release of PPP, poly(d,l-lactide-co-glycolide) (PLGA) was combined with the AOC in 2 mL of N-methyl-2-pyrrolidone and water solution (1.8/0.2 ratio). The release rates of all