Tailoring Release Profiles of BCS Class II Drugs Using Controlled Release Amorphous Solid Dispersion Beads with Membrane-Reservoir Design: Effect of Pore Former and Coating Levels.

Poor aqueous solubility is a major limiting factor during the development of BCS Class II drug candidates in a solid oral dosage form. Conventional amorphous solid dispersion (ASD) systems focus on maximizing the rate and extent of release by employing water-soluble polymeric crystallization inhibitors; however, they often encounter rapid supersaturation and solution-mediated phase transformation (SMPT). Therefore, in this work, a controlled release membrane was introduced onto ASD beads to mitigate the SMPT problem. A membrane-reservoir controlled release amorphous solid dispersion (CRASD) bead system was designed, and the effects of the coating thickness and pore former content on drug release profiles were investigated. CRASD beads were manufactured by spray-coating polyvinyl acetate with polyvinylpyrollidone (PVP) as a pore former onto sugar bead substrates layered with the ASD reservoir of celecoxib and PVP. Raising the pore former content and/or lowering the coating level imparted higher release rates and supersaturation levels. The extent of release, measured by the area under the curve, was greatest when an optimal balance between the release rate and peak concentration could be established, corresponding to a high pore former/high coating level combination. Attributed to a thicker membrane structure with a higher pore former, rapid initial release could be achieved, yet controlled gradually for several hours, avoiding the critical threshold where the onset of SMPT predominates. The greater membrane capacity to transiently immobilize drug molecules (i.e., preserve amorphicity) and gradually release drug over a prolonged duration may be key to balancing supersaturation on both sides of the membrane; hence coating variables should be tactfully selected to exploit this benefit.

Microscopic treatment of benign eyelid margin lesions with ultrapulse carbon dioxide (CO2) laser.

Surgical treatment of eyelid margin lesions is challenging, and few studies focused on laser therapy of such type of lesions. To evaluate the safety and effectiveness of ultrapulse CO2 laser treatment under a microscope for benign eyelid margin lesions, we performed microscopic ultrapulse CO2 laser treatment win 132 patients with benign eyelid margin lesions for cosmetic reasons. Measurements included cosmetic results, complications and patients' satisfaction. Eighty lesions involved the gray line and 24 lesions were in the lacrimal region. All patients achieved satisfactory cosmetic and therapeutic outcomes. Eyelid contour recovered well with no scar and no malposition. No secondary epiphora was noted after the lesions adjacent to the lacrimal punctum were removed. At the end of follow-up, only 2 patients had mild hypopigmentation and only 1 patient required repeat laser therapy for recurrence. It turned out that ultrapulse CO2 laser treatment under a microscope is a dependable, safe, and effective method for the treatment of benign eyelid margin lesions. It is an excellent alternative to traditional surgery, especially for lesions involving the gray line or positioned in proximity to the lacrimal punctum. It is beneficial for simplifying the treatment, improving the cosmetic result, and maintaining eyelid function.

[Magnetic resonance signal features of superparamagnetic iron oxide with different particle size and concentration].

OBJECTIVE: To investigate the magnetic resonance (MR) signal features of superparamagnetic iron oxide (SPIO) with different particle size and concentration. METHODS: The superparamagnetic iron oxide with different concentration and particle size was scanned by magnetic resonance; T1, T2 and T2(*) values of each group were recorded to evaluate the features of MR signals. RESULTS: The T1 value of SPIO with different particle size had negative linear relationship with concentration. In low concentration the T2 and T2(*) values were elevated markedly with the particle size decreased; while in high concentration the T2 and T2(*)values were elevated gently with particle size decreased. lg(T2), particle size and concentration of SPIO had linear relationship. CONCLUSIONS: SPIO affects magnetic resonance signal mainly with effect on T1 and T2. T2 value can be regarded as the major detection index in the magnetic resonance scan of SPIO. There is a linear relationship among particle size, SPIO concentration and lg(T2) value.

[Construction of a plant effective expression vector containing the gene of hepatitis B virus surface antigen].

OBJECTIVE: To construct a plant effective expression vector driven by a fruit specific promoter for the expression of hepatitis B virus surface antigen (HBsAg), to further improve the expression of exogenous gene in plant, and to prepare for the development of an effective anti-hepatitis vaccine. METHODS: Tomato fruit-specific promoters' gene 2A12 and E8 were respectively introduced to pBPFOmega7 to form pB2A12 and pBE8. The DNA fragment containing HBsAg-s gene from plasmid YEP-HBs was inserted respectively into pB2A12 and pBE8 to form pB2A12-HBs and pBE8-HBs. The fragment containing "p35S+2A12+Omega+HBsAg-s+Tnos" of the pB2A12-HBs was sub-cloned into plasmid pCAMBIA1301 to yield the reconstructed plant binary expression plasmid pCAM2A12-HBs, and the fragment containing "p35S+E8+Omega+HBsAg-s+Tnos" of the pBE8-HBs was sub-cloned into plasmid pCAMBIA1301 to yield the plasmid pCAME8-HBs. The inserted gene HBsAg and fruit-specific promoters in the reconstructed plant binary expression vectors were confirmed by sequencing. Then, pCAM2A12-HBs and pCAME8-HBs were directly introduced into Agrobacterium tumefaciens strain EHA105. RESULTS: Digestion with restriction enzymes proved that all recombinant vectors had the inserts with expected length of the target fragments, and the sequencing results were confirmed correct. CONCLUSION: In this study, plant expression vector containing HBsAg gene driven by fruit specific promoter and CaMV35s promoter was successfully constructed.