Advances in encapsulating gonadotropin-releasing hormone agonists for controlled release: a review.

Gonadotropin-releasing hormone (GnRH) agonists are peptides consisting of nine or ten amino acid residues. GnRH agonists have been applied in the therapy of sexual hormone disorders like prostate cancer, endometriosis, uterine myoma, central precious puberty, and in-vitro fertility. Treatment is achieved by continuous hormone intake and long-term agonists administration, which is usually associated with poor patient compliance. Because GnRH agonists that are administered with the parenteral route are broken down by peptidase, their half-life is short. As a result, developing sustained release for the drug delivery system is significant. Even though some drugs have been successfully delivered with long-acting release microspheres and approved by the Food and Drug Administration (FDA), some challenges remain. This review highlighted current approaches to encapsulate GnRH agonists into delivery systems and strategies encountered during the loading process. Moreover, the following sections provide strategies to improve the release profile, and animal and human studies were summarised.

Preparation of novel ropivacaine hydrochloride-loaded PLGA microspheres based on post-loading mode and efficacy evaluation.

Low encapsulation efficiency of the drug usually exist in hydrophilic drug which was embedded by hydrophobic materials directly in traditional method. In order to solve this problem, a novel preparation strategy which called "post-loading mode" was innovatively designed in this study: ropivacaine hydrochloride (ROP), a hydrophilic drug used in the field of anesthesia and analgesia, was encapsulated into the pre-prepared porous Poly (lactic-co-glycolic acid) (PLGA) microspheres; the porous PLGA microspheres (PLGA-Ms) with self-healing characteristic were used to obtain ROP-PLGA-Ms (with particle size around were 38 µm), in which drug loading (DL) was 8.72%. A rat sciatic nerve block model was established to evaluate the efficacy of ROP-PLGA-Ms. Exparel®, a bupivacaine liposome suspension approved by the FDA, was defined as reference agents in this study. The results showed that the injection of ROP, Exparel®, and ROP-PLGA-Ms were injected to the peripheral sciatic nerve could lead to motor dysfunction and sensory nerve block unanimously, and the onset time was less than 10 min for all cases. In addition, in comparison with ROP injection and Exparel®, the nerve block time of ROP-PLGA-Ms was significantly prolonged (P < 0.05). Effective analgesia duration of ROP-PLGA-Ms was about 5 h, 2.5 and 1.7 folds longer than that of ROP injection and Exparel®, respectively. The rats in each group could recover eventually within 8 h after administration. H&E showed that no inflammatory reaction was observed at the injection location. Analysis of blood biochemistry showed an insignificant difference between the microsphere experimental group and the negative group, which further indicated the safety of microsphere bioformulation.

Preparation and evaluation of amphipathic lipopeptide-loaded PLGA microspheres as sustained-release system for AIDS prevention.

At present, AIDS drugs are typical inhibitors that cannot achieve permanent effects. Therefore, the research of blocking HIV infection is essential. Especially for people in the high-risk environment, long-term prevention is important, because HIV can easily infect cells once the drug is interrupted. However, there is still no long-acting AIDS prevention drug approved. Hence, the purpose of this study is to prepare a fusion inhibitor loaded poly(d, l-lactic-co-glycolic acid) (PLGA) microspheres as a sustained-release system for long-term AIDS prevention. As the HIV membrane fusion inhibitor (LP-98) used in this research is amphiphilic lipopeptide, W1/O/W2 double-emulsion method was chosen, and premix membrane emulsification technique was used for controlling the uniformity of particle size. Several process parameters that can impact drug loading efficiency were summarized: the concentration of LP-98 and PLGA, and the preparation condition of primary emulsion. Finally, the microspheres with high loading efficiency (>8%) and encapsulation efficiency (>90%) were successfully prepared under optimum conditions. Pharmacokinetic studies showed that LP-98-loaded microspheres were capable to continuously release for 24 days in rats. This research can promote the application of sustained-release microspheres in AIDS prevention, and the embedding technique used in this study can also provide references for the loading of other amphipathic drugs.

Recent research and development of local anesthetic-loaded microspheres.

Local anesthetic drugs are widely used in postoperative analgesia, local nerve block in surgery, and in the therapy of chronic pain. Due to their short half-time, a single administration of local anesthetics merely maintains the nerve block for several hours, which cannot meet the long-term analgesia effect needed in clinical treatment. In order to break through this limitation of local anesthetics, research work regarding controlled drug release from microspheres has attracted broad and current interest. This review introduces the recent research and development in local anesthetic-loaded microspheres for future clinical applications, where for an efficient microsphere formulation, the most critical aspects are an optimum preparation method, a high loading efficiency, and an ideal release rate. This review first summarizes the recent preparation methods of local anesthetic-loaded microspheres, which includes emulsion-solvent evaporation, spray-drying, microfluidic droplets, and premix membrane emulsification technology. Next, strategies for increasing the loading efficiency of the drug in microspheres are reviewed based on the solidification conditions, polymer properties, microsphere formulation, including the external water phase, pH, and polymer concentration. Finally, the effects of the preparation conditions, material characteristics, particle characteristics, and hydrogel/microsphere composite systems on the controlled release behavior are summarized.