Natural and synthetic biopolymers are gaining popularity in the development of inhaled drug formulations. Their highly tunable properties and ability to sustain drug release allow for the incorporation of attributes not achieved in dry powder inhaler formulations composed only of micronized drugs, standard excipients, and/or carriers. There are multiple physiological barriers to the penetration of inhaled drugs to the epithelial surface, such as the periciliary layer mucus mesh, pulmonary macrophages, and inflammation and mucus compositional changes resulting from respiratory diseases. Biopolymers may facilitate transport to the epithelial surface despite such barriers. A variety of categories of biopolymers have been assessed for their potential in inhaled drug formulations throughout the research literature, ranging from natural biopolymers (e.g., chitosan, alginate, hyaluronic acid) to those synthesized in a laboratory setting (e.g., polycaprolactone, poly(lactic-co-glycolic acid)) with varying structures and compositions. To date, no biopolymers have been approved as a commercial dry powder inhaler product. However, advances may be possible in the treatment of respiratory diseases and infections upon further investigation and evaluation. Herein, this review will provide a thorough foundation of reported research utilizing biopolymers in dry powder inhaler formulations. Furthermore, insight and considerations for the future development of dry powder formulations will be proposed.

Background: Long-acting drug delivery strategies could augment pediatric human immunodeficiency virus (HIV) treatment effectiveness by bypassing population-specific challenges such as adherence. We harnessed pharmacokinetic (PK) modeling to develop a biodegradable, subcutaneous (SQ), reservoir-style implant for HIV treatment in 2–5-year-old children. Methods: Plasma was collected from New Zealand White rabbits over 30 h after a single intravenous (IV) bolus of bictegravir (BIC, 0.75 mg/kg), islatravir (ISL, 5 mg/kg) and/or emtricitabine (FTC, 30 mg/kg) then over a year after subcutaneous insertion of two to three implants eluting these antiretrovirals. Plasma antiretrovirals were quantified by HPLC-MS/MS and population PK models were fit to the IV PK profile to derive a mean unit impulse response (UIR). UIR was used to numerically deconvolve SQ absorption rate from the implant PK profile. SQ dosing rates were translated to pediatric plasma concentrations using published clinical PK parameters. Results: BIC, FTC, and ISL PK profiles were best described by two-compartment models. Each implant achieved quantifiable plasma concentrations for >360 days. Median SQ absorption rates (μg/day) at 3, 6 and 12 months of implantation were 116, 98 and 71 for BIC; 116, 37 and 5 for ISL; and 236, 116 and 24 for FTC. These 6-month dosing rates translated to pediatric plasma concentrations of 24 ng/mL BIC, 0.14 ng/mL ISL, and 0.7 ng/mL FTC. Conclusions: Our novel long-acting delivery platform exhibited antiretroviral SQ dosing rates for ≥6 months that are anticipated to achieve plasma concentrations in children within an efficacious range warranting further development for pediatric HIV treatment.

Background/Objectives: Multipurpose prevention technologies (MPTs) that combine protection against HIV and unintended pregnancy can improve women’s health outcomes by simplifying use and enhancing adherence. We developed a long-acting (LA) implant for the simultaneous and sustained delivery of the antiretroviral islatravir (ISL) and the contraceptive hormone etonogestrel (ENG). Methods: Using extruded poly-ε-caprolactone (PCL) tubing, reservoir-style implants were fabricated and evaluated in three configurations: (Group 1) a two-segment implant formed by joining separate ISL- and ENG-containing tubes; (Group 2) a single tube divided into two drug compartments by a heat-sealed PCL spacer; (Group 3) separate single-drug implants. In vitro release was assessed in phosphate-buffered saline at 37 °C, and safety and pharmacokinetic (PK) profiles were evaluated in New Zealand White rabbits (n = 4/group) over approximately 90 days. Results: The average ISL daily in vitro release rates for Groups 1, 2, and 3 were 29 ± 5 µg/day, 18 ± 5 µg/day, and 47 ± 8 µg/day, respectively, and ENG daily in vitro release rates were 39 ± 9 µg/day, 41 ± 8 µg/day, and 33 ± 7 µg/day. From day 28 through the end of the study, median (IQR) plasma concentrations were 0.22 (0.18–0.27) ng/mL, 0.28 (0.24–0.33) ng/mL, and 0.31 (0.28–0.33) ng/mL for ISL in Groups 1, 2, and 3, respectively, and 0.26 (0.21–0.31) ng/mL, 0.25 (0.16–0.47) ng/mL, and 0.30 (0.23–0.38) ng/mL for ENG in Groups 1, 2 and 3, respectively. Implants across all groups were well tolerated and demonstrated favorable local tolerability over the 90-day dosing period. Conclusions: Integration of multiple indications into a single platform capable of sustained release over an extended duration holds potential to address persistent gaps in women’s sexual and reproductive health needs.