Lectin-Functionalized Multiple Emulsions for Improved Cancer Therapy

Abstract

Fine-multiple emulsions bearing 6-mercaptopurine (6-MP) in internal aqueous phase were prepared by two step emulsification using sonication technique. It was coated with Concanavalin-A (Con-A) using carbodiimide method to obtain lectin-functionalized multiple emulsions. The Con-A coated multiple emulsion was characterized for antitumour activity on murine leukemia cell line L-1210 in vitro and compared with uncoated multiple emulsion and free drug. An increased uptake and cytotoxicity were observed for Con-A coated multiple emulsion in vitro. The IC50 was decreased upto 4-fold with Con-A coated emulsion. In vivo antitumour activity was seen by recording survival times of mice injected with L-1210 cells i.v. or i.p. The mean survival time was found to increase upon treatment with Con-A coated multiple emulsion. The tumour cell count in the peritoneal cavity was decreased significantly when animal was treated by i.p. route while there was no significant difference when it was treated by i.v. route. The normal peritoneal cells remained unaltered in number and blood parameters were also restored on treatment to tumour bearing mice. The formulation was found to be effective for the treatment of cancer.

Biological Activities of the Lectin, Abrin-a, Against Human Lymphocytes and Cultured Leukemic Cell Lines

“…The prerequisite step of these activities seems to be initiated by binding of lectins to the cell surface carbohydrate chains. Because of the carbohydrate specificity of lectins, many attempts have been made to elucidate the validity as markers of malignant cells and their potential clinical applications (5)(6)(7)(8).…”

Synthesis and in vitro Modeling and Characterization of Self-AssemblingDrug Conjugates for Targeted Medicinal Application

“…Adsorption (unfortunately this can produce differential dosage rates, through minor differences in surface activity of the species concerned), 3. Dissolution (solubilization and release rate depend on drug hydrophobicity), 4. Encapsulation (unfortunately this can give difficult to predict release rates with the multiple partitioning kinetics involved),…”

“…There are also the possibilities of using such nano-particulate systems with the intent of purposely creating drug-specific diagnostic biosensors to understand the uptake of drug particles based on highly specific surface "recognition" chemistry [20]. Lectin-functionalized multiple emulsions [4] are other novel examples where a targeting strategy and intelligent formulation fuse to produce a better and more specific product.…”

“…Conjugates have also been used directly in constructing pharmacologic models for use in mimicking cellular compartmentalization and this has been studied both for dendrimer [16,[23][24][25][26] and colloidal [4,6,25,[27][28][29][30][31][32][33] systems. Dendrimers are used widely in this field as they are polymers with a branch-like configuration [24], in the simplest scenario, but may also be constructed to form an array of architectures, many of which approximate to globules, spheroids or ellipsoidal cages and super-dense spheroids [11,16].…”

“…The objective in such cases is targeted delivery of the drug, bio-mimicry, replication and through development of new materials the means to build intelligent targeting capabilities, which improve on natural methods that are currently available [4]. Organic conjugates of formulation aids, associated drugs and chemical entities such as technetium, 99 Tc, used in radiotherapy [5] are used ubiquitously in medicine for diagnosis and as surgical aids.…”