MANUFACTURING OF TPM SUITABLE FOR HUMAN USE

腹膜癌在美国是主要的健康问题。有超过23万例新的癌症病例是由腹膜腔器官引起的。制药公司通常专注于静脉或口服给药。然而，由于肿瘤的血液灌流不足和间质液体压力高，全身治疗往往不能为实体肿瘤提供足够的药物水平。另一方面，在NIH资助的多项随机试验中，腹膜内化疗(IP)显示出令人印象深刻的生存优势。由于缺乏批准的IP产品，这些早期研究使用的是静脉制剂。这种方法有两个局限性：(A)限制药物对肿瘤外围的渗透会降低IP治疗较大肿瘤(&gt；1厘米)的疗效，以及b)IP治疗与感染(由于留置导管)和高局部药物水平的毒性(腹痛)有关。这些问题阻碍了IP疗法的广泛使用，尽管其疗效已被证明。

Peritoneal cancers are major health concerns in the US. There are over 230,000 new cases of cancers arising from organs in the peritoneal cavity. Pharmaceutical companies generally focus on drugs given by intravenous or oral administration. However, systemic therapy often does not deliver sufficient drug levels to solid tumors due to inadequate blood perfusion and high interstitial fluid pressure in tumors. On the other hand, intraperitoneal (ip) chemotherapy has demonstrated impressive survival advantage in multiple NIH-funded randomized trials. Due to the lack of approved ip products, these earlier studies had used intravenous formulations. This approach has two limitations: (a) restricted drug penetration to the tumor periphery diminishes the efficacy of ip treatment in patients with larger tumors (>1 cm), and b) ip therapy is associated with infection (due to indwelling catheter) and toxicity from high local drug levels (abdominal pain). These problems have prevented wide-spread use of ip therapy in spite of the demonstrated efficacy.