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Folate receptors (FRs) are expressed in vast majority of cancers. Selective targeting of the FRs is, therefore, one of the most popular and sought-after strategies for improving the efficacy of cancer therapeutics. Variety of approaches involving folate conjugation to several well-known and novel, nontoxic, biodegradable, and biocompatible (co)polymers have been attempted and successfully applied to a large number of nanoparticulate drug delivery systems (micelles, liposomes, nanoparticles, quantum dots, mesoporous silica-based materials, and others) in the last decade-and-a-half. Standard and novel synthetic approaches were utilized for the conjugation, followed by the formulation of the drug delivery modality. In most of the cases, the targeted system lived up to its reputation, validating its usefulness in targeted cancer therapeutics. The present review summarizes the progress and state-of-the-art synthetic methodologies for folate conjugation to (co)polymers, drugs, and nucleic acids. The limitations of the FR targeting are discussed in brief to give the reader the other side of the story. Finally, the information on marketed folic acid conjugates highlight their industrial applications.

Background: Gefitinib (GEF), the kinase inhibitor, is presently available as tablets to be taken orally in high doses of 250-500 mg per day due to its poor solubility. The solubility issues affect not only its onset of action but also the bioavailability. These drawbacks foresight the need to have an alternate dosage form, preferably a sustained release formulation. Methods: In the present study, microparticles were prepared by emulsion solvent evaporation using PLGA 50:50 (GEF-PLGA MP). A 32 factorial design was used to optimize the critical quality parameters to the set mean particle size in the range of 7.4±2.5 µm and entrapment efficiency of 80%. SEM microscopy of the prepared microparticles confirmed to have a spherical smooth shape. The GEFPLGA- MPs sustained the release of GEF for 72 hours. The first-order kinetics ruled the mechanism of drug release and was predicted to follow Fickian diffusion. Result: Anticancer efficacy was judged by the cytotoxicity studies using the L132 lung cancer cells. MTT assay showed 3-fold enhanced cytotoxicity of GEF loaded microparticles against L132 cells as compared to plain GEF. Conclusion: It was concluded that gefitinib can be efficiently loaded into the biodegradable polymer PLGA to provide sustained release of the drug.

In the present study Quality by design (QbD) principles were applied in formulating microparticles of erlotinib HCl (ERL), a lipophilic anticancer drug by spray drying. The study was done such that the QbD approach would demonstrate efficient feasibility in formulating the product and achieving the desired sustained release profile from the microparticles. After defining the quality target product profile (QTPP), the use of risk assessment by Ishikawa diagram assisted in identification of three risk factors namely the concentrations of polycaprolactone (PCL) and polyvinyl alcohol (PVA), and inlet temperature of spray dryer. A Box-Behnken design was used to study the effect of these three screened factors on particle size and drug encapsulation efficiency and sustained release duration. The multivariate DoE was able to show the impact of critical process parameters and critical material attributes on critical quality attributes (CQAs) and came out with a suitable design space which would yield the desired quality responses. The optimized formulation by the QbD approach gave promising IC50 values against the lung cancer cells (A549) indicating improved therapeutic efficacy and effective sustained release potential of the formulated microparticles.

Sumatriptan succinate, a serotonin 5-HT agonist, commonly used for migraine has erratic absorption from the gastrointestinal tract following oral administration and undergoes first-pass metabolism, resulting in a low bioavailability. The present study was undertaken to formulate fast-dissolving films of sumatriptan succinate meant to be quickly dispersed in the mouth. Films were prepared by solvent casting method and characterized for thickness, folding endurance, elongation, surface pH, and content uniformity. A 32 factorial design was used to optimize the in vitro dispersion time of films, and in vitro dissolution study was studied to determine the drug release. Ex vivo buccal permeation study was carried out using goat buccal mucosa mounted on a modified Franz diffusion cell. The optimized in vitro dispersion time for both the type of films was ∼30 s. The in vitro drug dissolution was complete in 90 s for both types of films. Thirty-eight percent of the drug was permeated from the hydroxy propyl methyl cellulose (HPMC) film, and about 42 % was permeated from maltodextrin film in 30 min. Such fast-dissolving films of sumatriptan succinate would mediate the release of drug and would be potentially useful for the treatment of migraine where quick onset of action is required.

The human body is a massive nanoscale molecular communications network composed of billions of interacting cells Drug delivery is an important application of molecular communication. Nanogels are aqueous dispersions of nanoscale size formed by cross-linking of hydrophilic polymers, capable of retaining large amounts of water yet remaining insoluble and maintaining a three-dimensional structure. Nanogel structure enables easy attachment of vector groups for effective communication with cells to reach the desired targeted site. This chapter highlights communication of drug loaded nanogels for targeting cancer through receptors. The chapter critically discusses receptors like- integrin αvβ3, EphA2, folate, Hyaluronan and monoclonal antibody for communication with nanogels.

Hydrogels are promising polymeric network capable of sustaining the release of drug but have a major limitation for encapsulation of hydrophobic drugs.This study was undertaken to encapsulate etoposide in poloxamer 407-based thermosensitive hydrogels with an aim to sustain its release.Etoposide-loaded hydrogels were prepared by the cold method and optimized for encapsulation efficiency (EE) by a 3(2) factorial design. Poloxamer 407-poloxamer 188 hydrogel (E-P407-P188) and poloxamer 407-poly(ethylene glycol) (E-P407-PEG) hydrogel were characterized for SEM, swelling, sol-gel phase transition and injectability study.In E-P407-P188 hydrogel the EE of 75% could be obtained and in E-P407-PEG hydrogels the EE was 84%. The SEM images showed a porous structure. The release of ETO was sustained up to 48 h by E-P407-PEG hydrogel and 24 h by E-P407-P188 hydrogel. The drug release was governed by first-order kinetics and followed Fickian diffusion mechanism in both the cases.Such injectable thermosensitive hydrogel of etoposide could be effectively used for continuous release of drug to the tumor and surrounding tissues.