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Aim: Garcinol (GAR)-loaded cationic nanoliposomes were developed to achieve potential antitumor efficacy on B16F10 melanoma cells in vitro and in vivo. Materials & methods: Two different phospholipids namely, distearoyl phosphatidylcholine (DSPC) and dipalmitoyl phosphatidylcholine (DPPC) were used in formulation to elucidate the difference in cellular uptake, cytotoxicity, in vivo tumor uptake (by scintigraphic imaging after technetium-99m radiolabeling) and therapeutic efficacy. Results: Different in vitro protocols, for example, MTT assay, apoptosis study, gene expression analysis, chromatin condensation and cytoskeleton breakdown analysis in B16F10 cell lines as well as scintigraphic analysis and tumor inhibition studies (B16F10 tumor xenograft model) revealed superiority of GAR-DPPC than GAR-DSPC and free GAR in melanoma prevention. Conclusion: Cationic nanoliposomal formulations could be a future medication for skin cancer treatment.

Betulinic acid, a plant secondary metabolite, has gained significant attention due to its antiproliferative activity over a range of cancer cells. A promising betulinic acid analogue (2c) with better therapeutic efficacy than parent molecule to colon carcinoma cells has been reported. Despite impressive biological applications, low aqueous solubility and bioavailability create difficulties for its therapeutic applications. To overcome these lacunae and make it as a promising drug candidate we have encapsulated the lead betulinic acid derivative (2c) in a polymeric nanocarrier system (2c-NP) and evaluated its in vitro and in vivo therapeutic efficacy. Apoptosis that induces in vitro antiproliferative activity was significantly increased by 2c-NP compared to free-drug (2c), as assured by MTT assay, Annexin V positivity, JC1 analysis and cell cycle study. The therapeutic potential measured in vitro and in vivo reflects ability of 2c-NP as an effective therapeutic agent for treatment of colon carcinoma and future translation to clinical trials.

Targeted drug delivery has become attention in chemotherapy during the last decade. The principle of chemotherapy seeks maximum effect to the desired site and the minimum impact to other undesired sites of action. The nanoparticulated drug delivery system progressed a lot in this aspect in the last twenty years. Plant-derived natural products and their semisynthetic analogues boosted chemotherapy through their excellent mechanistic approach to killing cancer cells. Keeping in mind the available molecular targets in colorectal carcinoma (CRC), in this article, we proposed a peptide conjugated novel polymeric nanoparticle to deliver garcinol against colorectal carcinoma. Integrin binding peptide iRGD, sequence c(CRGDKGPDC), has been selected as a targeting moiety, as most CRC overexpress integrins. We encapsulated garcinol in biodegradable polymeric nanoparticle (PLGA)-conjugated with iRGD peptide on the particles' surface, and analyzed its (iRGD-GAR-NP's) in vitro and in vivo antineoplastic potential against CRC in a comparative way with gracinol (GAR) and garcinol-loaded PLGA nanoparticles (GAR-NP). In vitro cellular studies on human CRC cell lines, HCT116 and HT-29, revealed the superior cytotoxic potential of iRGD-GAR-NP over GAR and GAR-NP. The IC

Curcumin (CUR), an antioxidant with p-glycoprotein inhibiting activity may be encapsulated with gemcitabine (GEM) as nanosuspension to enhance its anticancer potentiality synergistically. Folate conjugated single (CUR/GEM) and dual (CUR + GEM) drug-loaded nanoformulations were prepared and evaluated for P-glycoprotein-1 (pgy-1) gene resistance, followed by in vitro cellular uptake and cytotoxicity assay in cells. The in vivo biodistribution and scintigraphic imaging was done after radiolabeling the nanoparticles with 99mTechnetium (99mTc). The tumor inhibition study was conducted in nude mice bearing MDA-MB-231 xenografts. The folate conjugated dual drug formulations (FCGNPs) gave better results in suppressing the pgy-1 gene and also showed higher cellular uptake, cytotoxicity, apoptosis, and cell cycle arrest. The radiolabeled nanoformulations were highly stable and FCGNPs showed higher accumulation in the MDA-MB-231 tumor region than folate unconjugated dual drug NPs (CGNPs) as evidenced by scintigraphic imaging and biodistribution studies. The in vivo therapeutic efficacy of FCGNPs was higher compared to unconjugated and respective single-drug formulations. Two drugs in one platform lower breast adenocarcinoma by lowering drug resistance and improving cytotoxic effects.

Nanomedicine has gained tremendous attention in medical professionals owing to its smart strategies of treatment and huge applications in healthcare. Nanomedicine is mainly used for drug delivery with special attention to drug targeting, their excellent properties of high drug loading, sustained drug release, surface tunability, surface modification possibilities, and unique surface properties. A major portion of nanomedicine has been occupied by nanocarrier systems. For diagnosis and therapeutic purposes, nanoparticles, nanoliposomes, dendrimers, and other nanoparticulate devices have been reported for treatment/diagnosis of diseases. Several nanomedicines with emerging therapeutic efficacy have been already commercially available and many more are in pipeline. Despite their impressive therapeutic benefits, some critical challenges are associated with their transition from laboratory to clinical usage. Toxicity caused by nanoformulated drug is the most adverse barrier for its broad range of application. In this chapter, we have reported different nanocarriers available for their diversified applications in the management of several diseases, with a special emphasis on recently published reports, clinical evidence, and, their toxicity and safety concerns.

Betulinic acid (BA) was discovered as a cytotoxic agent in the early 1990s. Since then, this compound was extensively explored in search of its antiproliferative potency. Due to poor aqueous solubility, it was derivatized in several ways to improve its bioavailability along with discovering highly cytotoxic analogues toward cancer cells. Many of these betulinic acid derivatives were attempted to deliver through novel drug delivery systems to improve therapeutic efficacy, to reduce undesired side effects, and to enhance dosage efficacy. In this chapter, we have discussed about different betulinic acid derivatives with significant anticancer properties and their nanoformulated delivery approaches to combat against various cancer types.

The cytotoxic drug gemcitabine (GEM) has been conjugated to receptor-binding peptides to target melanoma tumors. A hexapeptide having a Lys–Gly–His–Lys sequence (pep-1), an octapeptide with an Arg–Gly–Asp–Lys–Gly–His–Lys sequence (pep-2), a GEM-conjugated Lys–Gly–His–Lys peptide (GEM–pep-3) and a GEM-conjugated Asp–Gly–Arg peptide (GEM–pep-4) were synthesized and characterized. In vitro uptake of fluorescently labeled GEM–pep-3 and GEM–pep-4 on B16F10 cells was investigated. Fluorescence microscopy studies demonstrated significant uptake of GEM–pep-3 in the B16F10 mouse melanoma cell line. The peptides and GEM-coupled peptides were radiolabeled with [(99m)Tc(CO)(3)(H(2)O)(3)](+) and examined for in vitro cell binding in the B16F10 melanoma cell line and in vivo biodistribution and scintigraphic studies in a B16F10 melanoma tumor-bearing mice model. In vitro cellular uptake studies and biological evaluation confirmed significant deposition of GEM–pep-3 at the melanoma tumor site. The MTT assay depicted higher cytotoxic behaviour of GEM–pep-3 than free GEM. A considerable amount of cell apoptosis was also observed in B16F10 cells. Finally, the in vivo therapeutic efficacy study revealed a significant decrease in tumor growth in the GEM–pep-3-treated animal model. These studies reveal enough potentiality of GEM–pep-3 to treat melanoma and underline the need for further evaluation.

Corticosteroids commonly prescribed in asthma show several side-effects. Relatively non-toxic andrographolide (AG) has an anti-asthmatic potential. But its poor bioavailability and short plasma half-life constrain its efficacy. To overcome them, we encapsulated AG in nanoparticle (AGNP) and evaluated AGNP for anti-asthmatic efficacy on murine asthma model by oral/pulmonary delivery. AGNP had 5.47% drug loading with a sustained drug release in vitro. Plasma and lung pharmacokinetic data showed predominantly improved AG-bioavailability upon AGNP administered orally/by pulmonary route. Cell numbers, IL-4, IL-5, and IL-13 levels in broncho-alveolar lavage fluid and serum IgE content were reduced significantly after administration of AGNP compared to free-AG treatment. AGNP-mediated suppression of NF-κβ was predominantly more compared to free-AG. Further, pulmonary route showed better therapeutic performance. In conclusion, AGNP effectively controlled mild and severe asthma and the pulmonary administration of AGNP was more efficacious than the oral route.