ABSTRACT
Colorectal cancer (CRC) is one of the deadliest malignancies in the US, ranking fourth after lung, prostate, and breast cancers, respectively, in general populations. It continues to be a menace, and the incidence has been projected to more than double by 2035, especially in underdeveloped countries. This review seeks to provide some insights into the disease progression, currently available treatment options and their challenges, and future perspectives. Searches were conducted in the PubMed search engine in the university's online library. The keywords were "Colorectal Cancer" AND "disease process" OR "disease mechanisms" OR "Current Treatment" OR "Prospects". Selection criteria were original articles published primarily during the period of 2013 through 2023. Abstracts, books and documents, and reviews/systematic reviews were filtered out. Of over 490 thousand articles returned, only about 800 met preliminary selection criteria, 200 were reviewed in detail, but 191 met final selection criteria. Fifty-one other articles were used due to cross-referencing. Although recently considered a disease of lifestyle, CRC incidence appears to be rising in countries with low, low-medium, and medium social demographic indices. CRC can affect all parts of the colon and rectum but is more fatal with poor disease outcomes when it is right-sided. The disease progression usually takes between 7-10 years and can be asymptomatic, making early detection and diagnosis difficult. The CRC tumor microenvironment is made up of different types of cells interacting with each other to promote the growth and proliferation of the tumor cells. Significant advancement has been made in the treatment of colorectal cancer. Notable approaches include surgery, chemotherapy, radiation therapy, and cryotherapy. Chemotherapy, including 5-fluorouracil, irinotecan, oxaliplatin, and leucovorin, plays a significant role in the management of CRC that has been diagnosed at advanced stages. Two classes of monoclonal antibody therapies have been approved by the FDA for the treatment of colorectal cancer: the vascular endothelial growth factor (VEGF) inhibitor, e.g., bevacizumab (Avastin®), and the epidermal growth factor receptor (EGFR) inhibitor, e.g., cetuximab (Erbitux®) and panitumumab (Verbitix®). However, many significant problems are still being experienced with these treatments, mainly off-target effects, toxic side effects, and the associated therapeutic failures of small molecular drugs and the rapid loss of efficacy of mAb therapies. Other novel delivery strategies continue to be investigated, including ligand-based targeting of CRC cells.
ABSTRACT
Pancreatic cancer is fast becoming a global menace and it is projected to be the second leading cause of cancer-related death by 2030. Pancreatic adenocarcinomas, which develop in the pancreas' exocrine region, are the predominant type of pancreatic cancer, representing about 95% of total pancreatic tumors. The malignancy progresses asymptomatically, making early diagnosis difficult. It is characterized by excessive production of fibrotic stroma known as desmoplasia, which aids tumor growth and metastatic spread by remodeling the extracellular matrix and releasing tumor growth factors. For decades, immense efforts have been harnessed toward developing more effective drug delivery systems for pancreatic cancer treatment leveraging nanotechnology, immunotherapy, drug conjugates, and combinations of these approaches. However, despite the reported preclinical success of these approaches, no substantial progress has been made clinically and the prognosis for pancreatic cancer is worsening. This review provides insights into challenges associated with the delivery of therapeutics for pancreatic cancer treatment and discusses drug delivery strategies to minimize adverse effects associated with current chemotherapy options and to improve the efficiency of drug treatment.
ABSTRACT
This study examined the effectiveness of niosomes loaded with levofloxacin in treating Pseudomonas aeruginosa (American Type Culture Collection-ATCC 27853) infections in Sprague Dawley rats since these infections are becoming more common and resistant to treatment. Levofloxacin entrapped in niosomes was prepared using the thin-film hydration method and was assessed for in vitro release and stability. Three groups of six (6) animals were infected with a lethal dose of Pseudomonas aeruginosa via the intraperitoneal (Ip) route. At six (6) hours postinfection, the animals were treated with either drug-free niosomes (control), free levofloxacin (conventional), or levofloxacin trapped in niosomes (Ip) at a dose of 7.5 mg/kg/once daily. Blood was collected via tail snips on days 0, 1, 3, 5, 7, and 10 for complete blood counts and viable bacterial counts (CFU/µl). At day 10, the animals were sacrificed, and the kidney, liver, and spleen were harvested for bacterial counts. The niosomes showed a sustained drug release profile and were most stable at 4°C. All animals in the control group succumbed to the infection; one animal from the conventional group died, and all niosome treated animals survived at day 10. The mean lymphocyte count (×109) was lower for the niosome (7.258 ± 1.773) versus conventional group (17.684 ± 10.008) (p < 0.03) at day ten (10). Neutrophil counts (×109) were lower for the niosome (2.563 ± 1.609) versus conventional (6.2 ± 6.548) (p < 0.02) groups. Though CFUs in the bloodstream were comparable for both treatment groups, the niosome treated group showed a significant reduction of CFUs in the liver, kidney, and spleen versus the conventional group (1.33 ± 2.074) vs (5.8 ± 3.74) (p < 0.043), (1.5 ± 2.35) vs (9.6 ± 8.65) (p < 0.038) and (3.8 4.71) vs (25.6 14.66) (p < 0.007), respectively. These findings indicate that niosome is promising as a drug delivery system in treating systemic infections, but further work using niosomes with surface modification is recommended.
ABSTRACT
Tropical starches from Dioscorea dumetorum (bitter) and Dioscorea oppositifolia (Chinese) yams were acetylated with acetic anhydride in pyridine medium and utilized as polymers for the delivery of repaglinide in microsphere formulations in comparison to ethyl cellulose. Acetylated starches of bitter and Chinese yams with degrees of substitution of 2.56 and 2.70 respectively were obtained. Acetylation was confirmed by FTIR, 1H NMR spectroscopy. A 32 factorial experimental design was performed using polymer type and drug-polymer ratio as independent variables. Particle size, swelling, entrapment and time for 50% drug release (t50) were dependent variables. Contour plots showed the relationship between the independent factors and the response variables. All variables except swelling increased with drug: polymer ratio. Entrapment efficiency was generally in the rank of Bitter yam>Ethyl cellulose>Chinese yam. Repaglinide microspheres had size 50±4.00 to 350±18.10µm, entrapment efficiency 75.30±3.03 to 93.10±2.75% and t50 3.20±0.42 to 7.20±0.55h. Bitter yam starch gave longer dissolution times than Chinese yam starch at all drug-polymer ratios. Drug release fitted Korsmeyer-Peppas and Hopfenberg models. Acetylated bitter and Chinese yam starches were found suitable as polymers to prolong release of repaglinide in microsphere formulations.
