**5. Conclusion**

*Pharmaceutical Formulation Design - Recent Practices*

prolonged the cell-killing effect of DOX.

delivery of therapeutics [77–79].

strated pH-sensitive drug release behavior.

while minimizing its systemic toxicity. The resulting microgels exhibited sensitivity to the pH and ionic strength of the surrounding environment and demonstrated that DOX was efficiently loaded into the microgels and released in a controlled fashion via an ion exchange mechanism. The antitumor activity of the released DOX was assessed using a human chordoma cell line revealed that OPF-SMA microgels

Tripahi et al. [74] developed a pH-sensitive intragastric floating polymer micro-

gel beads containing clarithromycin for the treatment of peptic ulcer. The optimized formulation successfully maintained minimum inhibition concentration of clarithromycin at the infection site and potentially allowed penetration of the drug inside the mucus gel. Varma et al. [75] have chemically modified guar gum (GG) as a pH-sensitive copolymer and formulated intestinal-targeting esomeprazole magnesium (ESO) nanoparticles (NPs). Polyacrylamide-grafted guar gum copolymer was synthesized by free radical polymerization, and ESO-loaded pH-sensitive NPs were prepared by nanoemulsification polymer cross-linking method. In vitro release studies showed pH-dependent drug release. The pH-sensitive NPs resisted

drug release in acidic pH and delayed the release in alkaline environment. In another study novel pH-responsive poly(methoxyethyl metacrylate-coitaconic acid) microgels were fabricated and evaluated for controlled and extended

delivery of model acid labile drug (esomeprazole). The designed microgels successfully protected the drug from acidic environment of the stomach, with potential intestinal drug delivery over an extended period of time. Thus, suggesting p(MEMA-co-IA) micro-hydrogels as good candidate of an orally administrated site-specific and controlled drug delivery system, such as proton-pump inhibitors, proteins, and peptides [76]. In similar studies p(hydroxyethyl methacrylateco-itaconic acid) microgels, poly(2-ethyl hexyl acrylate-co-IA) microgels, and poly(butyl acrylate-co-itaconic acid) microgels showed pH-responsive swelling and drug release behavior with maximum release at pH 7.4 and negligible release at pH 1.2 suggesting the potential use of these drug delivery system for oral intestinal

A novel 5-aminosalicylic acid (5-ASA)-loaded pH-sensitive poly(methoxy ethylene glycol-caprolactone-co-methacrylic acid-co-poly(ethylene glycol) dimethacrylate) microgels were prepared for treatment of ulcerative colitis. The microgels were found to be shrunk at pH 1.2 and expanded at pH 7.4. Safety evaluation of microgels was conducted by maximum tolerated dose (MTD) method. The 5-ASA/microgels were used to treat ulcerative colitis in mice, and free 5-ASA was used as positive control. It was found that 5-ASA has good efficacy for treating ulcerative colitis, and microgels entrapping 5-ASA could significantly enhance the colon targeting to improve its efficacy [80]. Xua et al. [81] fabricated novel biodegradable and pH-sensitive microgels based on poly(*ε*-caprolactone)-pluronic-poly(*ε*-caprolactone)-dimethacrylate, methyl acrylic acid, and poly(ethylene glycol)dimethacrylate cross-linked with N,N′-methylenebisacrylamide. Hydrophilic model drug (vitamin B12) was loaded to investigate in vitro release profile; the developed drug delivery system demon-

Lowman et al. [82] studied the use of poly(methacrylic-*g*-ethylene glycol) (P(MMA-*g*-EG)), a hydrogel microparticle that responds to a change in pH for the transport of orally administered insulin. This drug is a peptide labile to proteolytic degradation in the acidic stomach. Thus this pH-responsive carrier protected insulin in the acidic environment of the stomach as a result of the intermolecular interaction that prevented the hydrogel from swelling. But once the microparticles reached alkaline and neutral environments, namely, the intestine, the interaction that occurred previously was lost, and the pore size of the hydrogel increased, thus

**92**

allowing insulin release.

This chapter has attempted the compilation of the advances in the field of stimuli-responsive microgel technology and their application in controlled release drug delivery carriers. The ultimate goal for controlled drug release is to maximize therapeutic activity while minimizing the negative side effects of the drug. In this regard, versatile micro- and nanoscale delivery approaches based on smart polymers have already been established to seek the distinct advantages in drug delivery. However, the new polymers and nanocarriers definitely require extensive consideration of toxicological and immunological issues, which are often ignored during the research phase.
