In situ floating hydrogel for intravesical delivery of adriamycin without blocking urinary tract.
Drug solution is commonly used in conventional intravesical instillation. However, most of them would be easily eliminated by voiding, which significantly limit their efficacy. Recent advances in intravesical drug delivery are to use hydrogels as drug reservoir to extend the drug residence time in bladder. However, because of the high viscosity of hydrogel, urinary obstruction is usually existed during the intravesical instillation. To overcome these, we developed a floating hydrogel for the delivery of Adriamycin (ADR). The floating hydrogel was made of ADR, thermosensitive polymer (Poloxamer 407) and NaHCO₃, which was liquid at low temperature, whereas formed gel at high temperature. In the presence of H⁺, NaHCO₃ decomposed and produced CO₂ that attached on the surface of hydrogel and helped the hydrogel float on the urine. Hence, the urinary tract will not be blocked. Meanwhile, the encapsulated ADR released in a controlled manner. These results suggest that the floating gel may have promising applications in intravesical therapy for bladder cancer.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China; The Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210093, China; Medical School of Nanjing University, Nanjing, 210093, China.
Tingsheng
T
Lin
Jinhui
J
Wu
Xiaozhi
X
Zhao
Huibo
H
Lian
Ahu
A
Yuan
Xiaolei
X
Tang
Sai
S
Zhao
Hongqian
H
Guo
Yiqiao
Y
Hu
D000283:Administration, Intravesical; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D063566:Biodegradable Plastics / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000009:adverse effects* / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D004339:Drug Compounding; D005260:Female; D020100:Hydrogels / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D020442:Poloxamer / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D020011:Protective Agents / Q000008:administration & dosage / Q000737:chemistry; D017510:Protein Folding; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000008:administration & dosage / Q000737:chemistry; D000075462:Serum Albumin, Human; D017693:Sodium Bicarbonate / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D013046:Specific Gravity; D014018:Tissue Distribution; D014524:Urethral Obstruction / Q000209:etiology / Q000517:prevention & control*; D001743:Urinary Bladder / Q000378:metabolism
C422455:ALB protein, human; D000903:Antibiotics, Antineoplastic; D063566:Biodegradable Plastics; D003692:Delayed-Action Preparations; D020100:Hydrogels; D020011:Protective Agents; D012709:Serum Albumin; D020442:Poloxamer; D004317:Doxorubicin; D017693:Sodium Bicarbonate; D000075462:Serum Albumin, Human
biodegradable polymers; cancer chemotherapy; controlled release; drug delivery systems; intravesical instillation; thermal gels