Recently, the media has been awash with news of this new promising preventive therapy for HIV — Lenacapavir (Yetzugo), a first-in-class, twice-yearly subcutaneous injection given for pre-exposure prophylaxis of HIV-1 infection in adults and adolescents weighing over 35kg and at risk of HIV-1 acquisition. Developed by Gilead Sciences and approved by the US FDA in 2024, in my opinion, this is probably the 8th wonder of the world. Initially priced at over $28k in the United States, through a series of agreements with international donors and generic manufacturers, access to this transformative medication is finally made available to millions of people at risk in LMICs. However, recent media development in Nigeria gives me more questions than hope.

Straight to the point

Earlier this week, I saw posts making rounds on social media announcing the availability of Lenacapavir. The posts are optimistic; they speak to better compliance for patients, they highlight its 100% efficacy in preventing HIV, some colour it as a protective coat in case you were in a relationship with a PLHIV. They all end the same way — with a price and a sort of gratitude and credit to NGOs for “subsidising it for Nigerians.” People are glad. Reshares are plenty. Attached to some of these posts are calls to action — DM, let’s deal. One pharmacist on my contact list says, “hopefully we spread this way to other diseases like cancer.” Every post says that it costs 58,000 naira (roughly $40, at the current exchange rate). Who is setting the price?

But I am livid. And shocked. Angry to say the least.

As I shared on my (very, very private status), the current Lenacapavir social media rounds are probably a good yardstick for highlighting the systemic failure in the Nigerian healthcare system. Also, it is a sign of how deprecating this pharmacy practice is becoming. I do not know where the market has gotten its current stock from, but I wonder how one can openly market a medication that hasn’t been registered by NAFDAC. Albeit, one whose stock should only be accessed (at least for the time being) through a coordinated National Health Program led by the Ministry of Health. As far as I know, neither NAFDAC has granted an emergency use authorisation (EUA) or marketing authorisation, nor NACA or the Federal Ministry of Health announced a roll-out. The recent news, if true and if indeed individuals are already making purchases, challenges public health safety, exacerbates already existing health inequality and undermines the integrity of Nigeria’s pharmaceutical supply chain.

My verdict is that these social media announcements are a marketing/PR campaign to stimulate consumer demand. Sadly, a commercial stunt disguised as a public health education.

Lenacapavir should not follow the Ozempic story

I do not want Yetzugo or its generic to follow the Ozempic/Wegovy path— where unregistered products cannibalised the market. As we speak, Ozempic (mostly stock smuggled from other regional markets) is akin to an OTC medication — you can walk into most stores or order online. Even more fearful are the reports of improperly stored, falsified and substandard products branded as Ozempic flooding the market (NAFDAC even put out an alert late last year). It is a choas right now. I would hate for Lenacapavir to follow the same path. I am strongly opposed, even as a pharmacist, to the idea of having individuals purchase the product over-the-counter or through digital mediums.

The access problem

A recent article by Nigeria Health Watch accurately describes everything you need to know and how much “access” is the challenging puzzle in future rollout. Like any other long-acting PrEP medication, Lencapavir requires a carefully thought-out protocol:

• who should benefit from it? which populations are at risk for HIV-1 acquisition and therefore would derive greater benefit?
• how do we ensure baseline HIV testing (using RDT or other methods) before drug administration? (It carries a black box warning about developing resistance if administered to HIV-positive status individuals)
• are you the right patient? the need for professional training for dose administration? (Yeztugo does come with its safety risks — severe injection site reactions such as ulcers and necrosis if not injected properly)
• how do we ensure proper STI counselling before and after dose administration? (Lencapavir won’t protect you from everything, just HIV-1)
• how do we establish a follow-up infrastructure to ensure patients complete their doses? (you selling it for 58k, can you ensure this?)
• pharmacovigilance systems? You just can’t stress this enough — robust post-market surveillance is required to ensure continued effectiveness and safety.
• how do we ensure product quality? (any unregistered product is already a quality risk. In this case in particular, where most stockpile is through donors and bilateral agreements, I am scratching my head.)

These are not questions I think those with commercial interests are asking. Additionally, we need to decenter urban interests in public health conversations. I believe most of the people spreading this news are living in urban centres and of a particular socioeconomic class. If we let commercial interests drive access to this medication, those who really need it would be left out. At 58k (help me ask: is it for a dose or 2 doses?), a sex worker and single mother living in a refugee camp in Benue state would probably not be able to afford that. I’m not sure commercial interests would consider rural communities or rural settlements in the larger metropolis. If indeed I can send a DM on WhatsApp and purchase Lencapavir for 58k today, I doubt I would be able to purchase it at the same price by June. Who knows, it could cost 200k by December?

And didn't Gilead make the agreement with the Global Fund and the Medicines Patent Pool? Where are our social media heroes obtaining their stockpile from? I have my suspicions, but let me feign ignorance, lol.

Conclusion

Basically, all I am trying to say is that international donors and innovators have done us a favour. Now we have to do what’s right. The recent social media announcements are not a sign of improving healthcare access. Instead its a reminder of how tough and fragile pharmaceutical regulation is in this region. Additionally, if true, it poses a threat to medication quality, safety, healthcare access and supply chain integrity. I do not expect anyone to market or stimulate consumer demand for Lencapavir at this time.

Selah.

A weekly review of academic papers focused on nanomedicine, drug delivery science and any other area I find interesting.

This week I read 2 recent interesting papers from the JCR, one original research paper and a review.

1. 3D printed sex-specific medicines: Excipient-mediated modulation boosts systemic drug exposure by more than three-fold in male rats. (Laxmi Prasanna Nandiraju et.al., 2026)

Published in Journal of Controlled Release, Volume 390, 10 February 2026

I can’t tell how many ideas ran through my head when I first read the title of this paper. Sex-specific medicines? How? These were compelling questions that framed the discussion in this remarkable study. Our fundamental understanding of medicines is that they are one-size-fits-all; what works for Emeka would work for Chinenye. But what if certain medications produce better effects in one sex than in the other?

Additionally, growing evidence suggests excipients (the non-active components of your medications) are also “active” in some sense. Excipients on their own can change how an active drug moiety interacts with the body (targets, transporters, tissues), how it is absorbed and distributed and can pose safety risks on their own. Here in this paper, the role of an excipient, polyethylene glycol (PEG), in modulating observed sex-specific effects of a drug is reported.

Lastly, there is the use of 3D printing technology to produce optimised tablet formulations (printlets in this case) for pharmacokinetic investigation in animal models. 3D printing is cool to hear, especially if you are a CS geek. It’s interesting to see more 3D printing modalities in pharma scientific literature as it presents a frontier in personalised medicine, though I’m curious about regulatory activities (say GMP of 3D printed tablets) when these technologies gain widespread clinical translation.

Study Methodology

I’ll spare you the time and energy by not boring you with details of the study’s formulation, animal PK studies, analytical techniques or the 3D printing process — though you can find that by reading the paper here. The drug utilised in the study was Silodosin, a BCS Class III drug — the Biopharmaceutics Classification System, BCS groups drugs into four classes based on their solubility and permeability, which are important criteria in the successful development of drug molecules. Silodosin was selected as it is indicated in BPH, a urological condition prevalent in men (sex-specific disease), exhibits a low oral bioavailability of 32% (how much of the drug in the pill that is released to the body) and also because it is a substrate of the P-glycoprotein transporter. The P-glycoprotein is a specialised protein found in many tissues of your body that works as an efflux pump — basically, it throws things out. This is good as it can throw out toxins and unwanted materials, and it’s a bad thing also because it throws out drugs that the body really needs (Silodosin, for example).

The authors created different solutions of the drug, Silodosin and an excipient, PEG-2000 (varying concentrations) and tested these solutions on male and female Wister rats. Results indicated the 1% w/v solution gave the best PK parameter effects — Cmax, AUC and Tmax (do I have to explain these terms?).

Then they designed 3D printed tablets using this same concentration (1% w/v) containing the drug, Silodosin and PEG-2000. They also designed a control group, which was printlets without PEG-2000. Afterwards, characterisation of the printlets by LC-MS, HLPC, TGA, FTIR, In-vitro disintegration, In-vivo dissolution and Pharmacokinetics was done.

Key Results and Conclusions:

The study investigation was able to conclusively demonstrate the sex-specific effects of silodosin due to its interaction with the P-gp transporter. This was evidenced initially in an observed 36% increase in AUC (extent of drug exposure) in male Wistar rats when administered a Silodosin drug solution containing 1% w/v PEG-2000. In female rats administered the same solution, the change in AUC was only a 3% increase. Furthermore, on administration of the 3D-printed optimised printlets to test and control animal groups, a 213% increase in AUC was demonstrated in male Wistar rats who received the test printlet compared to the control group and also a corresponding 42% increase in AUC in female rats compared to the control group. The use of Wistar rats to demonstrate sex-specific effects is also justified due to their comparable expression of intestinal P-gp to humans. The results of the study are important for the clinical development of medicines. Recognising the effect of sex, industry and regulators lay more emphasis on understanding these considerations when developing new medicines. Additionally, the paper highlights the potential for personalised medicine and drug delivery.

Critical Analysis

While this study was able to demonstrate impressive PK enhancement using excipients and laid a solid foundation in shaping our understanding and development of sex-specific personalised medicines, I believe some critical gaps limit its potential clinical translation. I highlight some of my questions and thoughts below:

a. Mechanistic Validation of P-glycoprotein modulation: While it is well documented in the literature that the sex-specific effects of P-glycoprotein, it is hard to directly infer that the observed PK effects were wholly due to direct modulation of P-gp by PEG-2000. Could the effect noticed (213% increase in AUC) be caused by other biological interactions? As there were no direct P-gp measurements, I doubt that we can concretely prove that the excipient directly inhibits the transporter protein. PK estimates are not enough to claim mechanistic modulation. The question of how PEG-2000 enhances silodosin absorption and interacts with P-gp remains unanswered.

b. Clinical Dose and Animal Species Translation: The authors justify the relevance of the animal models, Wistar rats, in this study by stating similar intestinal P-gp expression to humans, which should allow clinical translation. However, there exist significant differences between Wistar rat GI physiology and that of humans, thus limiting clinical translation of any such effects. Additionally, the effect of genetic variability (P-gp polymorphisms), hormonal influences, and inter–individual differences would need to be considered during clinical translation efforts.

Dose extrapolation to humans also raises questions. Applying FDA guidance for estimation of starting dose, using body surface area (BSA) normalisation, the Human Equivalent Dose (HED) of the formulation in this study would be 630mg of Silodosin.

where, HED = Animal dose (mg/kg) x (Animal Km/Human Km)
and the Rat dose = 55.6 mg/kg (assuming an average weight of 250g per rat and a 12.5mg dose per rat).

then, HED = 55.6 x (6/37) = 9mg/kg (or 630mg for a 70kg human)

For emphasis, the clinical dose of Silodosin is 8mg/day, and here in the study, the tested equivalent dose is many times higher than what is obtainable in clinical practice. Additionally, assuming a 10-fold reduction due to a safety factor, the Minimum Recommended Starting Dose (MRSD) of the formulation would be 63mg, which is still 8x higher than the approved clinical dose. The question to answer here is, does PEG-2000 produce the same PK effects from modulation when formulations are tested at clinical doses?

c. Observed variability in Female Rats: I believe the variability in PK estimates (high Tmax variability) in female Wistar rats in the study could be a biological signal of confounding effects. The effect of estrous cycles on P-gp and GI motility could be a contributing factor and should ideally be explored in further PK studies. Furthermore, if hormonal effects are present in female rats, the clinical implications of such findings are profound.

d. Analytical Rigour: The study utilised pharmacopeial standards in characterisation of 3D-printed tablets (USP Dissolution method, Disintegration), yet I was left wondering if there were specific analytical standards required for 3D-printlets, noting their unique characters and dissimilarity to normal oral solid dosage forms. If we are going to see more 3D printing personalised medicine, then pharmacopeial standards must be developed alongside, tailored specifically for this unique dosage form.

e. Unidirectional Application: The study demonstrates male-specific enhancement but doesn’t explore female-optimised formulations for female-prevalent diseases. Could the same sex-specific effects be observed in female-driven diseases such as endometrosis, and the role of target modulation and personalised medicine in addressing this?

f. Regulatory Uncertainty: I think this is where I had the most questions, as the regulatory implications when considering clinical translation of the study insights are unclear. How would regulators evaluate GMP compliance of 3D-printed medicines? How would bioequivalence be evaluated when PK is sex-dependent? Safety evaluation of PEG-2000 is also missing, especially at such high therapeutic doses if translated. Additionally, if we now see some excipients as “active” components, could regulatory frameworks adapt to require Drug-Excipient interaction studies, the same way we have Drug-Drug interaction risk assessments? How about sex-specific adverse event reporting, as we could see different safety profiles in male and female populations? New labelling regulations? (for example, Silodosin SmPC, product information, and packaging insert make no discussion of observed sex effects.)

2. Equip your vehicle for the right terrain: Using features of local pathology to guide engineering of targeted drug delivery systems. (Taylor Brysgel et.al., 2026)

Published in Journal of Controlled Release, Volume 389, 10 January 2026.

Innovation in new medicines has gotten better and more promising, and so has the delivery of new medicines has become smart and complex. The idea behind this paper is simple (but not so simple, though) — if you must get to your final destination, you must understand where you are going and prepare adequately. Consider a drug delivery system as an F1 race car. You understand that to hit top speeds and to even navigate easily at these ultra-high speeds, your vehicle has to be ‘abnormal’. For one, your vehicle has to have the lowest centre of gravity possible, and the tyres have to be of a certain size and quality to enable a strong grip on the race tracks. It is the understanding of the mission that guides the design choices when building the vehicle.

Loosely translating this analogy to drug delivery, our understanding of the body’s physiology, anatomy, and local disease states should guide the choices made during the design of delivery technologies to produce the best therapeutic outcomes. The authors explain this in detail in this review, highlighting local pathologic features that can be exploited by drug delivery systems.

The authors utilised the pulmonary (lungs) system as a case study to drive their conclusions.

Key Ideas:

Throughout the review, one could note recurring themes of size, shape, hemodynamics, flexibility, pathological targeting, biomimetics and stimuli-response. These are central design choices to make when creating a drug delivery system for the pulmonary micro-vasculature. The shape of nanocarriers is an important consideration, as computational and microfluidic studies, as noted by the authors, demonstrate that rod-like shapes perform better than spherical-shaped carriers. This makes sense as rod-like shapes give a better hemodynamic fit, in my opinion. Size, though, offers notable advantages, as being too large would not allow passage through capillary spaces and too small might lead to higher clearance.

“For example, NCs smaller than 10 nm are typically cleared rapidly via renal filtration or through non-specific trans-endothelial transport. In contrast, particles larger than 200 nm are often sequestered by the mononuclear phagocyte system (MPS), particularly in the liver, spleen, and bone marrow, leading to reduced circulation time”

Flexibility of nanocarriers is a critical choice to make, as rigid particles behave poorly, and flexibility allows deformity and the ability to cross narrow spaces, avoiding entrapment. Pathological targeting involves exploiting local disease characteristics — in many pathological conditions, the body is dysregulated and opportunities present for active targeting. For example, the authors note that patients suffering from Acute Lung Injury, noted by pathological hallmarks such as lung inflammation, edema, hypoxia, reactive oxygen species (ROS) accumulation, there is also dysregulation in the lung endothelial structures and an increased expression of adhesion molecules. These opportunities are, in turn, exploited by drug delivery systems by engineering active targeting mechanisms for more precise treatment.

Till next week, Selah!

What I Read This Week

1. Optimizing lipid nanoparticles for fetal gene delivery in vitro, ex vivo, and aided with machine learning (Amr Abostait et.al., 2024):
In the application of lipid nanoparticles (LNPs) as a delivery carrier for gene therapy in congenital abnormalities during pregnancy, there is a need to ensure adequate transplacental transport, safety and efficient transfection. In this study, a library of LNPs was formulated and characterized for physicochemical parameters and further evaluated for cell viability, transplacental transport kinetics, toxicity, in-vitro transfection and ex-vivo transfection in rat fetal lung tissue. Data from transport studies (48 transport experiments, 189 transport data points, 19 input features) were used to train a pre-selected machine learning model (Random Forest**) to investigate the effect of LNP composition and process features on transplacental transport and gene transfection. ML model found a high zeta potential (ZP) as a key attribute for high placental transport and a low ZP as a predictor for low transport across the placenta. Based on the ML insights, LNP formulations were optimised for improved transplacental transport and siRNA transfection using 5 features — zeta potential, number of LNPs per cell, LNP size, mass of LNP per cell and PEGlyated lipid end-functional group.

2. Understanding, informing and defining the regulatory science of microneedle-based dosage forms that are applied to the skin (Maria Dul et.al., 2025):
Despite the increasing innovation and successful translation of microneedle-based devices and therapies in the clinic, the regulatory frameworks remain immature. The authors of the white paper form part of industry stakeholders in a regulatory working group (RWG) offering insights to guide the regulation of new microneedle development. The paper presents regulatory nomenclature — label names, technical vocabulary, classifications, definition of dosage form, identifying critical quality attributes (CQAs) to ensure consistent quality in the manufacturing of these dosage forms and prioritises CQAs that would require novel testing methods and specifications. A recommendation for the label name of such medicinal products was proposed as Microneedle Array Patch (MAP), though this is subject to regional regulatory interpretation and add-ons based on any additional components or functionality such products would possess. For example, a microneedle loaded with ibuprofen formulated for controlled release would probably be labelled as “Ibuprofen 400mg Microneedle Array System SR” in the US. Additionally, the paper attempts to define MAPs and what does not qualify as a MAP. Critical quality attributes are a key component of Quality-by-Design principles (QbD) and highlight parameters which ensure the quality of a pharmaceutical product. 20 CQAs were identified and ranked by criticality and priority to present 3 highly critical and high-priority CQAs. These CQAs — delivered dose, puncture performance, drug release/dissolution- would require the creation of novel or adaptation of previous testing methods and specifications. The future implications of the white paper are enormous for guiding further expansion in the regulatory frameworks for microneedle systems.

3. An oral liraglutide nanomicelle formulation conferring reduced insulin-resistance and long-term hypoglycemic and lipid metabolic benefits (Laxman Subedi et.al., 2025):
Management of type 2 diabetes (T2DM) often involves the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which are characterized by their poor oral bioavailability necessitating administration by subcutaneous injection. However oral delivery of GLP-1 RAs remains a frontier that could improve patient and therapeutic outcomes. In this paper, oral delivery of liraglutide (LRG) using bile acid nanomicelles (NMs) is studied for its impact on improving long-term hyperglycemia, lipid metabolism and reduction in insulin resistance. Various formulations were prepared and optimised with the LRG [1:2:4]-NM + non-ionic surfactant (n-dodecyl-β-D-maltoside; DDM) showing significantly improved performance than other formulation configurations. Delivery of LRG through bile acid derivative nanomicelles can be attributed to the activation of the apical sodium-dependent bile transporter pathway (ABST) which allows increased cellular uptake of LRG from the intestinal mucosa.

4. Applying the lessons learned from the COVID-19 pandemic to the next generation of nanocarrier-based vaccines (Giuseppe Bardi, 2024):
2020 was a breakthrough year in nanomedicine research, witnessing the use of nanocarriers in the delivery of SARS-COV-19 vaccines. The author highlights 3 key lessons we can adopt from this breakthrough experience; first, the need to prioritise improved nanocarrier characterization methods that ensure the efficacy and safety of vaccines. Secondly, the author discusses the potential for the application of nanocarriers for delivery to the lung mucosa to elicit immune responses. This is a limitation to current COVID-19 vaccines which can only prevent infection but cannot generate systemic immune responses. Lastly is optimizing nanocarrier properties such as surface chemistry to improve immune cell-target selectivity.

Learning Points

Reading the papers this week left me with questions as well as exposed the gaps in my foundational knowledge. For example, I pondered about how the decision to use DDM in the liraglutide study was arrived at. Besides my now increased appreciation for basic STEM research, studying the foundations of material chemistry, pharmaceutics and biophysics should now be a priority.

Looking Ahead

A paper I look forward to reading next week explores the dry powder inhalation of CRISPR-Cas9 nanoparticles in the treatment of lung disease. I might also seek out more foundational papers to plug some of the gaps in my head. selah.

Stats

Papers completed: 4/7

Average reading time per paper: 2.5 hours

**here’s a brief explanation of the random forest algorithm in case you need to geek out: https://www.geeksforgeeks.org/random-forest-algorithm-in-machine-learning/

What I Read This Week

1. Checkpoint Immunotherapy for Melanoma — offering Hope for care

This recent editorial by Brendan D. Curti highlights results from a 10-year phase 3 clinical trial of two oncology medications, nivolumab and ipilimumab. Nivolumab and ipilimumab are immune inhibitors of T cell regulatory checkpoints, PD-1 and CLTA-4. Clinical studies conducted in the early 2000s with either checkpoint agent showed significant survival benefits for patients with advanced melanomas. The editorial further highlighted the work by Wolchik et al. who conducted a randomised phase 3 trial with patients with previously untreated melanoma. Patients were assigned to one of 3 regimens — a combination therapy (nivolumab + ipilimumab followed by nivolumab maintenance therapy), ipilimumab monotherapy or nivolumab monotherapy. 10-year trial results found a median overall survival of 71.9 months and a melanoma-specific survival of more than 120 months in the combination therapy group. The results are promising and indicate greater survival benefits for immunotherapy modalities in solid metastatic tumours.

2. A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform

This was probably my favourite read of the week. The authors in this study designed a novel in-vitro model based on the fetal-maternal membrane. Here’s the gist: Pregnant women and fetuses are regarded as therapeutic organs because they are often excluded from clinical trials and are not considered in the development of new therapies for preterm birth. There are a myriad of reasons for this, one of which is due to the lack of pre-clinical data one can obtain from this population. Available pre-clinical models (i.e. murine and non-human primates) fail to simulate perfectly the uterine environment and thus safety cannot be guaranteed if you proceed to clinical stage trials. The authors in this study utilise photolithography to fabricate a silicone polymer-based organ-on-chip that models the multiple cells of the fetal-decidua-placenta membrane. The FMi-PLA-OOC was tested for cell morphology, fluid hydrodynamics, cell viability, cytotoxicity and trophoblast differentiation. FMi-PLA-OOC was further utilised to test an engineered EV-based (naturally occurring exosomes within 50- 150nm) anti-inflammatory agent (eIL-10) for its in-vitro efficacy, mechanism of action, cytotoxicity and cellular activation/suppression of inflammatory mediators. Data generated from this organ-on-chip model demonstrated the role of infection and inflammation of the fetal-maternal membranes in preterm birth and also the efficacy of EV-delivered anti-inflammatory agents in suppressing inflammatory mediators. The fetal organ-on-chip though with unique limitations is a pioneer innovation that could improve preclinical data in pregnancy-related therapeutics.

3. Exosomal delivery of NF-kB inhibitor delays LPS-induced preterm birth and modulates fetal immune cell profile in mouse models

4. Nanoceria as a non-steroidal anti-inflammatory drug for endometriosis theranostics

Looking Ahead

I’d be lying if I said being consistent wasn’t tasking. Next week I’d be reading papers across various themes. One of which I’m excited to get into explores the regulatory science of microneedle-based dosage forms applied to the skin. I also started reading a study utilising ML models to optimise in-vitro and ex-vivo properties of lipid nanoparticles (LNPs). It was a bit of a mental task to get through so I’d give it a shot again this week.

selah.

Stats

Papers completed: 4/7

Average Reading time per paper: 1.5hrs