Polymer-drug conjugates: Design principles, emerging synthetic strategies and clinical overview.

Adagen, an enzyme replacement treatment for adenosine deaminase deficiency, was the first protein-polymer conjugate to be approved in early 1990 s. Post this regulatory approval, numerous polymeric drugs and polymeric nanoparticles have entered the market as advanced or next-generation polymer-based therapeutics, while many others have currently been tested clinically. The polymer conjugation to therapeutic moiety offers several advantages, like enhanced solubilization of drug, controlled release, reduced immunogenicity, and prolonged circulation. The present review intends to highlight considerations in the design of therapeutically effective polymer-drug conjugates (PDCs), including the choice of linker chemistry. The potential synthetic strategies to formulate PDCs have been discussed along with recent advancements in the different types of PDCs, i.e., polymer-small molecular weight drug conjugates, polymer-protein conjugates, and stimuli-responsive PDCs, which are under clinical/preclinical investigation. Current impediments and regulatory hurdles hindering the clinical translation of PDC into effective therapeutic regimens for the amelioration of disease conditions have been addressed.

Polyethylene oxide and its controlled release properties in hydrophilic matrix tablets for oral administration.

Polymers are excipients that modify the rate of drug release from pharmaceutical dosage forms. Hydrophilic polymer-based controlled drug delivery system is more advantageous as compared to the conventional delivery system as it reduces the dosing frequency, improves therapeutic efficacy, reduces side-effects, and probably enhances patient compliance. Polyethylene oxide (PEO), a nonionic hydrophilic polymer, is one of the most widely used polymers for extending the drug release. This review mainly focuses on the PEO marketed by, but not limited to, The Dow Chemical Company under the trade name of POLYOXTM. It is commercially available polyethylene oxide polymer existing in various molecular weight and viscosity grades depending upon the application. This study essentially discusses chemistry, physicochemical properties, and the impact of formulation and processing variables on the release of drug from hydrophilic PEO matrix tablets. Moreover, it also summarizes the stability, patents, and regulatory perspectives of POLYOX that can further influence the future developments of controlled release dosage forms.

Formulation of polymeric nanoparticles of antidepressant drug for intranasal delivery.

Aim: The manuscript describes the performance of nanoparticles loaded with antidepressant drug for nose-to-brain drug delivery. Materials & methods: Poly-lactic-co-glycolic acid-loaded nanoparticles of agomelatine were prepared by nanoprecipitation method using poloxamer 407 as stabilizer. The process parameters were optimized using factorial design. Results: The drug-loaded nanoparticles having low particle size (<200 nm) with narrow size distribution and required zeta potential (-22.7 mV) to avoid aggregation showed sustained release profile and were found to have higher permeability as observed from ex vivo studies when compared with plain drug suspension. Histopathology test showed that the optimized formulation was free from nasal toxicity on the goat nasal mucosa. Pharmacodynamic study showed significant reduction in immobility time in rats treated with the formulation which indicated antidepressant activity of the formulation. Conclusion: The prepared agomelatin-loaded poly-lactic-co-glycolic acid nanoparticles showed prominent antidepressant activity by nose-to-brain delivery as observed from various studies.

Solid lipid nanoparticles as an efficient drug delivery system of olmesartan medoxomil for the treatment of hypertension.

The aim of the current investigation was to develop solid lipid nanoparticles of olmesartan medoxomil using hot homogenization method to improve its oral bioavailability. Central composite design was applied to optimize the formulation variables; lipid X1 (Glyceryl monostearate) and surfactant X2 (Poloxamer: Tween 80). The particle sizes were in the nanometer range and spherical shaped for all prepared solid lipid nanoparticles formulations and the zeta potential absolute values were high, predicting good long-term stability. In vitro study of olmesartan loaded solid lipid nanoparticle exhibited controlled release profile for at least 24 h. The rate and extent of drug diffusion was studied using dialysis sac, rat's stomach and intestine tissues; study demonstrated that drug release from the solid lipid nanoparticles was significantly higher than drug suspension. In vivo pharmacokinetic study of olmesartan loaded solid lipid nanoparticles revealed higher Cmax of 1610 ng/mL, higher AUC of 15492.50 ng/mL and increased relative bioavailability by almost 2.3 folds compared to marketed formulation. These results clearly indicate that olmesartan loaded solid lipid nanoparticles are shown to have enhanced bioavailability and effective therapeutic result and thus would be an excellent way to treat hypertension. Hence, these solid lipid nanoparticles could represent as a great potential for a possible alternative to conventional oral formulation in the treatment of hypertension.

Formulation and statistical optimization of intravenous temozolomide-loaded PEGylated liposomes to treat glioblastoma multiforme by three-level factorial design.

The aim of the presented study was to develop PEGylated liposomes of Temozolomide (TMZ) that provide optimum drug concentration at tumor site. Reverse phase evaporation (REV) method was used to prepare TMZ-loaded PEGylated liposomes. Formulation was optimized by using design expert software by 32 factorial design. The physicochemical properties including size, morphology, entrapment efficiency, drug loading, etc. of formulated liposomes were evaluated. Finally, the optimized formulation was selected for in vitro drug release and stability study. In vivo pharmacokinetic study in rats showed that TMZ-loaded PEGylated liposomes leads to 1.6-fold increase in AUCTotal in blood and 4.2-fold increase in brain as compared to free drug solution. This formulated PEGylated liposomes offers a promising approach for treatment of Glioblastoma Multiforme.